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IRC 

681 

HTc 




NATIONAL 

HEART, BLOOD VESSEL, LUNG, AND BLOOD 

PROGRAM 



FIRST ANNUAL REPORT OF THE 

DIRECTOR OF THE 

NATIONAL HEART AND LUNG INSTITUTE 



^ 00 D 



FEBRUARY 13, 1974 



U.S. DEPARTMENT OF HEALTH. EDUCATION, AND WELFARE 

Public Health Service 

National Institutes ol Health 

N.itinn.ii Heart and Lung Institute 



FIRST JWNUAL REPORT OF THE 

DIRECTOR OF THE 

NATIONAL HEART AND LUNG INSTITUTE 



SUBMITTED TO 
THE PRESIDENT OF THE UNITED STATES 

FOR TRANSMITTAL TO 

THE CONGRESS OF THE UNITED STATES 

IN ACCORDANCE WITH PUBLIC LAW 92-423 



FEBRUARY 13, 1974 



U.S. DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE 

PUBLIC HEALTH SERVICE 

NATIONAL INSTITUTES OF HEALTH 

NATIONAL HEART AND LUNG INSTITUTE 



6¥l 



DEPARTMENT OF HEALTH, EDUCATION. AND WELFARE 

PUBLIC HEALTH SERVICE 

NATIONAL INSTITUTES OF HEALTH 

BETHESDA, MARYLAND 20014 



NATIONAL HEART AND LUNG INSTITUTE 



February 13, 1974 

The President 
The White House 
Washington, D. C. 

Dear Mr. President: 

I am pleased to submit to you for transmittal to Congress the first 
annual report on the National Heart, Blood Vessel, Lung, and Blood 
Program. It highlights the activities, progress, and accomplishments 
of the Program during the past calendar year and updates the Program 
Plan completed in May 1973. This report is prepared in response to 
Section 413(b) of the National Heart, Blood Vessel, Lung, and Blood 
Act of 1972 (Public Law 92-423, 86 STAT 679). 

The National Heart, Blood Vessel, Lung, and Blood Program is gaining 
momentum and interest. Contributing to its implementation, planning, 
and evaluation are thousands of scientists, physicians, and other 
health professionals across the United States; the National Heart and 
Lung Institute and its Advisory Council; other bureaus, institutes, 
and divisions of the National Institutes of Health; Federal agencies 
and departments both within and without the Department of Health, 
Education, and Welfare; and voluntary organizations and interested 
and committed citizens . 

The Program gives special emphasis to prevention of heart attacks, 
the greatest killer in our nation; high blood pressure education, since 
millions of our citizens do not know that they have it and that it can 
be treated; expansion of the attack on lung diseases, a heretofore 
neglected area; and the development of a national blood policy, a 
critical national need. Also, the previous emphasis on the control 
of sickle cell disease will be continued. 

We strongly agree with you that "Keeping People Healthy" is one of our 
nation's most important goals for the 1970' s, and appreciate your pledge 
to give "increased attention to the fight against diseases of the heart, 
blood vessels, and lung which account for more than half of the deaths 
in this country." 



Respectfully, 




Theodore Cooper, M. D. 
Director 



CONTENTS 

Page 

I. INTRODUCTION 1 

II. HIGHLIGHTS OF THE NATIONAL PROGRAM 7 

Highlights: Heart and Blood Vessel Diseases 11 

Highlights: Lung Diseases 15 

Highlights: Blood Diseases and Blood Resources 17 

III. STATUS OF PROGRAM AND UPDATED FIVE-YEAR PLAN 19 

Research 21 

Heart and Blood Vessel Diseases 23 

Lung Diseases 51 

Blood Diseases and Blood Resources 75 

Prevention, Control, and Education 97 

Heart and Blood Vessel Diseases 99 

Lung Diseases 105 

Blood Diseases and Blood Resources 110 

IV. PROGRAM COORDINATION 117 

National Collaboration 1 19 

Heart and Blood Vessel Diseases 120 

Lung Diseases 1 24 

Blood Diseases and Blood Resources 126 

International Collaboration 1 28 

V. MANPOWER DEVELOPMENT 131 

Heart and Blood Vessel Diseases 132 

Lung Diseases 133 

Blood Diseases and Blood Resources 134 

VI. IMPLEMENTATION OF OTHER PROVISIONS OF THE ACT 135 

National Research and Demonstration Centers 135 

Construction 136 

Mechanisms of Support 137 

Administrative Changes 138 

Program Review and Evaluation 139 

VII. RESOURCE ALLOCATION PLAN 141 

Fiscal Summary and Projections 142 

NHLI Staff Allocation Plan 148 

APPENDIX A - National Heart, Blood Vessel, Lung, and 
Blood Act of 1972 

APPENDIX B - Definition of Major Problem Areas 



I. INTRODUCTION 



I. INTRODUCTION 



The United States, despite its high state of technology, lags behind many other 
Western nations in the health of its citizens. In fact, it ranks 24th in the 
world with respect to life expectancy for men. The high mortality from heart 
and blood vessel diseases is the major contributing factor to this shortened 
life expectancy. 

The quality and composition of our environment are important to the maintenance 
of health — the air we breathe, the water we drink, the food we eat. We can live 
only a few minutes without oxygen, a few days without water, and a few weeks 
without food. Many of the diseases addressed by the National Program on Heart, 
Blood Vessel, Lung, and Blood Diseases are known to be related to the quality 
of our environment. The impact of these diseases, as compared to that of other 
diseases, is summarized in Table 1. 



Table 1. Ranking of Diseases According to Health Impact, United States, 1971 



DISEASE 


DAYS OF BED 
DISABILITY 


HOSPITAL 
DISCHARGES 


HOSPITAL 
DAYS 


RANK 


DAYS" 


RANK 


NUMBER" 


RANK 


DAYS" 


Influenza & pneumonia 
Upper respiratory 


1 
2 


206.241 
164.840' 


2 


1.311 


11 


3.444 


"Heart disease 


3 


93.137 


1 


1.390 


1 


17.921 


Arthritis 
Mental disorders 
Fracture! & dislocation? 
Malignant neoplasms (Cancerl 
Impairments ot back & spine 


4 

s 

6 
7 
8 


57.639 
41.965 
35.626 
32.374 
31.895 


12 
5 
3 
6 


217 

695 

1.249 

646 


9 
3 
2 

4 


3.837 
16.273 
17,097 

7.785 


" 'Hypertensive without heart involvement 

"Bronchitis 

"Asthma 

"Cerebrovascular disease 


9 

to 

II 
12 


27,476 
27.388 
25.997 
24.762 


9 

11 


314 
264 


12 

7 


2,780 
5.128 


Paralysis 

Diabetes 

Impairments of lower extremities 

Ulcer 


13 

14 
15 
16 


24.062 
23.739 
20.986 
17.669 


10 
8 


280 
492 


10 
6 


3.498 

5,245 


" "Emphysema 


17 


13.124 




- 






Hernia 

Gall madder 

Absence ol extremities 

Impairments of upper extremities 


18 
19 
20 
21 


11.948 
11.892 
7.347 
5.491 


4 

7 


728 
530 


8 
5 


4.836 
6.922 


OtU not #»i>iabkr SOURCE Unpublished Oil* Irom <ht Ninon*! Oni.i for Ht.lth Statistics 
In thousands 
*' AcSdlMMU by National Program 



Through the mandate provided by the National Heart, Blood Vessel, Lung, and Blood 
Act of 1972, the nation's scientific and medical resources are beginning to be 
mobilized in a national collaboration of Federal, non-Federal, and private organi- 
zations, as well as citizens at large. 

The initial Program Plan,* dated May 1, 1973, which was forwarded to the President 
and Congress, presented a broad program strategy for achieving improved health. 
This strategy is: 

" . . .to marshall national resources for promoting and restoring 
health, and for preventing and treating disease more effectively 
by: 

• Initiating an ordered sequence of coordinated 
program activities ranging from the acquisition 
of new knowledge to demonstration and control 
programs in the health care setting of the 
community 

• Providing adequate program evaluation before the 
application of existing knowledge to health care 
delivery systems 

• Evaluating the impact of implemented programs on 
the health of the American people." 

Within the broad strategy outlined above and in compliance with the National 
Heart, Blood Vessel, Lung, and Blood Act of 1972, a multifaceted National Pro- 
gram has taken shape. The scope of the evolving program ranges from fundamental 
studies of molecules inside single cells within the human system to studies of 
effects of pharmacological agents, to development and evaluation of new types of 
therapy involving advanced bioengineering concepts. It also includes studies of 
patient attitudes, behavioral studies, and investigations dealing with man's 
ability to cope with underwater and space environments, reaching into future 
vistas of mankind. 

In implementing this broad strategy, a number of basic factors having impact on 
all program components for the future, as well as the present were considered 



*The National Heart, Blood Vessel, Lung, and Blood Program was presented in five 
volumes; DHEW Publication Numbers are shown below: 

Volume I. National Heart and Lung Institute Summary (NIH 73-515) 
Volume II. Report of the National Heart and Lung Advisory Council 

(NIH 73-516) 
Volume III. Report of the Panel Chairmen (NIH 73-517) 
Volume IV. Panel Reports (NIH 73-518 - 73-521) 
Volume V. Program Analysis (NIH 73-522 - 73-524) 



and dealt with initially. During the past eight months since the Plan was ini- 
tiated, six major strategic actions have been taken by the National Heart and 
Lung Institute: 



1. Reorganization of the Institute's programs. 

2. Promotion of collaborative efforts. 

3. Creation of an Office of Prevention, Control, and Education. 

4. Development of guidelines for national centers. 

5. Analysis and evaluation of actions in the initial Plan. 

6. Review and assessment of goals, progress, and future 
challenges. 

These actions are outlined briefly below: 



REORGANIZATION 



NHLI activities have broadened considerably under the National 
Program. To meet these new responsibilities, the Institute has 
reorganized its entire program into divisions corresponding to 
the major heart, lung, and blood disease areas. This development 
is discussed in greater detail in Chapter VI. 



collaboration To most effectively utilize all of our national resources to combat 
heart, blood vessel, lung, and blood diseases, the NHLI has initi- 
ated and fostered collaborative programs involving many sectors of 
society. This activity has been promoted through the Interagency 
Technical Committee as well as other mechanisms, as elaborated in 
Chapter IV. 



PREVENTION. 
CONTROL. AND 
EDUCATION 



To implement a special provision of the National Heart, Blood 
Vessel, Lung, and Blood Act, the NHLI has created an Office of Pre- 
vention, Control, and Education. This office is responsible for 
disseminating health information and for public education activi- 
ties. It is also responsible for the prevention and control programs 
as outlined in Chapter III. 



NATIONAL 
CENTERS 



To expedite the further development of the National Program 
throughout the country, explicit criteria and guidelines for the 
establishment of national research and demonstration centers have 
been developed and released for use by potential applicants. This 
action is described further in Chapter VI. 



ANALYSIS 
OF ACTIONS 
IN INITIAL 
PLAN 



During the past year, the NHLI has made a careful study of the 
material upon which the Actions in the initial Plan were based. 
As a result, a revised program structure of 22 elements (10 for 
heart and blood vessel diseases, 8 for lung diseases, and 4 for 
blood diseases and blood resources) was developed as illustrated 
in Table 2. This revised program structure is used in this report, 
in lieu of the 17-element structure of the initial Plan, to describe 
progress, update the Plan, and allocate proposed fiscal resources. 
Also, as a part of this study, each Action of the initial Plan has 
been examined for its relative importance to the total program. 
This report reflects several minor shifts in emphasis resulting 
from this analysis. 



REVIEW AND 
ASSESSMENT 
OF GOALS. 
PROGRESS. 
CHALLENGES 



Finally, with respect to the item above, a thorough review and 
assessment of Program Goals, Recent Progress, and Future Challenges 
have been carried out in each program area. The results of this 
assessment are reflected mainly in Chapter III. Actions of the 
initial Plan have been updated and some additional items have been 
included in the updated Plan. 



Table 2. National Heart, Blood Vessel, Lung, and Blood Program Structure 



HEART AND BLOOD VESSEL DISEASES 


1. 


Arteriosclerosis 


2. 


Hypertension 


3. 


Cerebrovascular Disease 


4. 


Coronary Heart Disease 


5. 


Peripheral Vascular Diseases 


6. 


Arrhythmias 


7. 


Heart Failure and Shock 


8. 


Congenital and Rheumatic Heart Diseases 


9. 


Cardiomyopathy and Infections of the Heart 


10. 


Circulatory Assistance 


LUNG DISEASES 


1. 


Structure and Function of the Lung 


2. 


Pediatric Pulmonary Diseases 


3. 


Emphysema and Chronic Bronchitis 


4. 


Fibrotic and Immunologic Lung Diseases 


5. 


Respiratory Failure 


6. 


Pulmonary Vascular Diseases 


7. 


Inhalation Diseases 


8. 


Respiratory Assistance 


BLOOD DISEASES AND 8L00D RESOURCES 


1. 


Bleeding and Clotting Disorders 


2. 


Sickle Cell Disease and Related Disorders of the Red Blood Cell 


3. 


Biomaterials 


4. 


Blood Resources 



This report on the National Program is the first annual report on the activities, 
progress, and accomplishments in the Program and is the first update of the 5-Year 
National Plan. It supersedes Volume I of the original Plan. In addition to shed- 
ding more light on the six strategic actions described above, the report covers 
the following topics: 



Chapter II. Highlights of the National Program 

Chapter III. Status of Program and Updated Five-Year Plan 

Chapter IV. Program Coordination 

Chapter V. Manpower Development 

Chapter VI. Implementation of Other Provisions of the Act 

Chapter VII. Resource Allocation Plan. 



The National Heart, Blood Vessel, Lung, and Blood Act of 1972 is reproduced in 
Appendix A. Definitions, full descriptions, and the mortality and morbidity 
impact of major problem areas have been reprinted from the National Heart and 
Lung Institute Summary (May 1, 1973) of the National Program and are presented 
in Appendix B with definitions of new problem areas added at the end. 

Insofar as possible, the report is presented in nontechnical language in order 
to communicate with interested laymen who may be unfamiliar with medical termi- 
nology. Where such terminology is unavoidable, effort has been made to provide 
clarification in the text of the report. Reference to the definitions and dis- 
cussions of major heart, blood vessel, lung, and blood problem areas contained 
in Appendix B will also be helpful to the lay reader in understanding the con- 
cepts discussed in this report. 



II. HIGHLIGHTS OF THE NATIONAL PROGRAM 



II. HIGHLIGHTS OF THE NATIONAL PROGRAM 



Collectively, heart, blood vessel, lung, and blood diseases cause more deaths 
than all other diseases in the United States combined. They have a devastating 
effect on the health of our citizens as well as on the nation's economy. More 
than 30 million Americans suffer from these diseases. Their impact in terms of 
national economic loss has been estimated at more than $40 billion a year. These 
figures, while impressive in terms of identifying the problem, fail to convey the 
seriousness of the social impact of these diseases — the dimensions of suffering, 
grief, disability, stress and hardship, and the effects these diseases have on the 
patient and the patient's family. 

Why do these diseases overwhelm our current health care system, and is there hope 
for a solution to the problem? The principal reason why they overwhelm our health 
care system is that we lack the necessary understanding to deal with them effec- 
tively. This understanding can be obtained through research. A second reason is 
that the results of medical research are sometimes not applied to the health care 
system as expeditiously as they might be. Thus, further medical research and the 
application of the knowledge gained through research offer substantial hope of 
reducing the devastating effects of heart, blood vessel, lung, and blood diseases 
in the future. Accordingly, the National Heart, Blood Vessel, Lung, and Blood 
Program focuses primarily on two types of efforts: (1) Research Programs, and 
(2) Prevention, Control, and Education Programs to bridge the gap between research 
findings and clinical application. Currently, the expenditures for research on 
these problems represent less than one percent of the total costs for these dis- 
eases. For instance, in the case of heart and blood vessel diseases, the estimated 
annual cost to the economy is more than $30 billion, while the total Federal expen- 
diture for research in this area in FY 72 was about $200 million.* Yet, medical 
research is the wisest investment that the nation can make to insure further prog- 
ress in the attack against heart, blood vessel, lung, and blood diseases. Thus, 
the common interest of everyone in our society dictates a high priority for the 
further development of the comprehensive National Heart, Blood Vessel, Lung, and 
Blood Program. 



*Volume I, National Heart and Lung Institute Summary, May 1973, p. 17 



A conceptual strategy for the National Program Plan was presented nearly one 
year ago in the National Heart and Lung Institute Summary, referred to earlier. 
This initial strategy provided the first approximation of the direction the 
program would take, its underlying principles, and its method of implementation. 
The strategy was not complete in concept or in operational detail — nor was it 
intended to be at this early stage. Each year as we gain more experience and 
knowledge in the planning, implementation, and evaluation of a major national 
program for biomedical research, the conceptual and operational aspects of the 
program will become clearer and more precise. In the initial program strategy, 
three underlying principles were outlined as summarized below: 

• The long-range goal must be to improve the health of the 
American people. 

• Programs for achieving this goal must be based on an 
orderly progression of sequenced activities from acqui- 
sition of fundamental knowledge to the application of 
existing knowledge. 

• Evaluation of the use of knowledge — both before its appli- 
cation in health care delivery and after to determine its 
impact on the health of the American people — will be the 
key to meeting national health goals. 

The major planning problem addressed during this past year has been how to trans- 
late abstract goals and principles, conceived at a policy-making level, into 
meaningful program activities involving thousands of individuals. In formulating 
an attack on this problem, we have reexamined the above principles and found them 
still viable. We have extended these principles conceptually into a more complete 
strategy. And we have begun to implement this strategy operationally. The 
updated program strategy, outlined below, gives increased attention to the impor- 
tance of the social and physical aspects of our human environment and their rela- 
tionship to health and disease. The operational steps taken to implement this 
strategy are described in Chapters III, IV, V, and VI of this report, and the 
estimated resources to put the plan into effect are presented in Chapter VII. 

In seeking solutions to the pressing health problems of heart, blood vessel, lung, 
and blood diseases, we are giving special recognition to the social and physical 
aspects of the human environment and their role in the development of these dis- 
eases. Also, the importance of the context of the total human environment to the 
success of the National Program is being considered in the planning, implementa- 
tion, evaluation, and coordination of the Program. 

Our modern technological society offers many choices of life style both for every- 
day working life and for the increasingly available leisure time. We live in an 
age characterized by specialization of labor, sophisticated machinery, complex 
systems of organization, and mass production. In communicating with the public 
and the health professions, the Program emphasizes how the choice of life style 
and physical environment, by individuals as well as communities, in fact may imply 
a choice of future health or disease of the heart and the lungs. Current and 
future program plans stress how disease might be prevented before the onset of 



catastrophic illness which may be beyond the reach even of modern medical tech- 
nology. Currently, the National Program gives special emphasis to five program 
areas described in detail in Chapter III and highlighted below: 



• Prevention of heart attacks — the greatest killer in 
our nation 

• High blood pressure education — millions of our citizens 
do not know that they have high blood pressure, that it 
may lead to serious complications such as stroke and 
death, and that treatment is available 

• Expansion of the attack on lung diseases — a heretofore 
neglected area 

• Development of a national blood policy — a critical 
national need 

• Methods of controlling sickle cell disease. 

Social change, brought about by the increasing use of rapid communication and 
transportation systems, has radically altered leisure and work activities, 
resulting in new health problems which fall within the scope of the National 
Heart, Blood Vessel, Lung, and Blood Program. 

Changing attitudes are directing our attention to long-neglected disease prob- 
lems particularly prevalent in certain population groups. Sickle cell disease, 
one of these problems, is receiving special emphasis in the National Program. 
Such programs, in addition to the need for medical expertise, require a high 
degree of knowledge about the special needs and desires of these patients. The 
great expense of providing available medical treatment, such as Factor VIII for 
patients with hemophilia, creates drastic social changes for the family of the 
victim. It may, in fact, condemn the family to life-long poverty. Social change 
is causing increasing numbers of elderly citizens, many of whom have cardiovas- 
cular or respiratory problems, to be without the aid of or proximity to their 
families in times of need. 

Socioeconomic factors play a role in the development of many diseases. While 
poverty is associated with increased infant, maternal, and overall mortality, 
the general affluence in the United States is thought to be associated with the 
high mortality rate from coronary heart disease and heart attacks. 

Social isolation is a problem in many parts of the United States, both in urban 
and rural areas. This often prevents the National Program from reaching those 
people who need it most. The Institute is paying particular attention to devel- 
oping lines of communication with community health resources and developing edu- 
cation and demonstration programs to alert the medical profession and the public 
to new methods of disease control and treatment in the local community. Speci- 
fically, the Institute is developing cooperative programs with Federal and non- 
Federal health agencies for the purpose of controlling, and in the long-term 
preventing, heart, blood vessel, lung, and blood diseases. One example is the 
National High Blood Pressure Education Program, discussed in Chapter III under 
Prevention, Control, and Education. 



Social mobility, particularly geographic mobility, creates problems which limit 
the timing of National Program efforts. An average of 18 percent of the total 
U. S. population- moves annually. This places restrictions on the length of time 
available for follow-up of patients participating in clinical studies to deter- 
mine the benefits of new treatments, such as the modification of diet in the 
therapy of heart disease. It further poses managerial problems in carrying out 
well-controlled studies in large free-living populations. The Institute is care- 
ful to take these factors into consideration in its planning of long-range clin- 
ical trials, such as the Multiple Risk Factor Intervention Trial discussed in the 
section on Arteriosclerosis in Chapter III. 

Our American culture and the quality of life in the United States appear impor- 
tant in increasing a person's susceptibility to heart and lung disease. For 
instance, in Denmark, Norway, and Sweden, the death rate from coronary heart dis- 
ease for men under the age of 55 is less than half that for the same age group in 
the United States. In Japan it is one-sixth that in our country. These interna- 
tional statistics indicate that the high death rates from coronary heart disease 
in the United States are neither necessary nor inevitable. Research has identi- 
fied a number of factors which appear important in increasing a person's suscepti- 
bility to heart and lung disease. Programs are being developed to modify these 
factors without disrupting our way of life. Specifically, the National Program 
emphasizes research, control, and education efforts on how heart and vascular 
disease might be prevented through changes in life style, and how such changes 
can be most effectively implemented. Good health is everyone's major source of 
wealth and happiness. The American public is generally not aware of the extent 
to which the individual can contribute to maintenance of good health and preven- 
tion of disease. Programs are underway to explore, develop, and evaluate the 
most effective means of motivating the public as a whole to take voluntary action 
which may be helpful in promoting personal health, preventing disease, and assur- 
ing prompt treatment of disease before a crisis situation develops. 

Urbanization and life stresses in general are being studied to determine how these 
factors affect the development of disease. Behavioral studies have indicated that 
certain types of individuals are more prone than others to develop heart and lung 
disease under conditions of similar stress. Periods of mental and environmental 
stress may thus be associated with an increased incidence of disease. However, 
the exact nature of these associations remains to be defined. 

In the case of lung diseases, the social habit of cigarette smoking is believed 
to be a prime factor in the etiology or exacerbation of both chronic bronchitis 
and emphysema — two chronic obstructive lung diseases which are on the increase 
in the United States. Smoking also contributes to environmental lung diseases 
and hypersensitivity lung diseases. Up to 20 percent of smokers have chronic 
obstructive lung disease, and almost all afflicted patients are smokers. Thus, 
one of the major goals of the National Program in the field of lung diseases is 
to modify the smoking habits of persons at risk of developing lung diseases and 
to extend successful anti-smoking programs to the general population. The Pro- 
gram also addresses the problem of pollution brought on by the technological 
revolution in the United States. This is a well-recognized problem in lung dis- 
ease, and one which may be regulated by society. The choice is ours. 



10 



In developing and evaluating highly sophisticated therapeutic modalities such as 
artificial circulatory assistance, the National Program has given a prominent 
place to nonmedical aspects of the human environment. Examples are public atti- 
tudes and social, ethical, legal, and other factors important in assessing the 
public impact and in ensuring the acceptance of the new treatment when it is 
introduced in practice. Behavioral scientists, ethicists, lawyers, economists, 
educational experts, and interested laymen are cooperating in the Program to 
identify nonmedical issues that may help or hinder this and other research, pre- 
vention, and treatment programs. 

The human environment also plays an important role in the National Program 
efforts to deal with the difficult problem of national blood resources. This 
entire program depends upon the willingness of human beings to donate blood 
for use by other human beings. High quality blood and blood products are essen- 
tial to effectively treat many diseases as well as to save the lives of injured 
individuals. To be able to supply sufficient quantities of any given blood 
product on a moment's notice requires many steps, from recruiting the donor 
to collecting the blood, separating it into its components, detecting and elimi- 
nating disease-causing agents, matching the components for compatibility with the 
recipient's blood, and administering the blood or blood component to the patient 
in a safe manner. In the United States, many different organizations are respon- 
sible for these operations. A major problem with the present system is the lack 
of uniform quality control of blood donations. The NHLI, in cooperation with a 
number of Federal and non-Federal agencies, is striving for an all-volunteer 
blood system. 

A comprehensive account of recent progress and future challenges for all program 
areas addressed by the National Program is presented in Chapter III of this report. 
Since Chapter III is rather technical in content, the use of medical terminology 
is unavoidable. To provide the lay reader with an overview of prominent program 
developments, highlights of recent progress and future challenges are presented 
below in lay language for each of heart and blood vessel diseases, lung diseases, 
and blood diseases and blood resources. 



HIGHLIGHTS: HEART AND BLOOD VESSEL DISEASES 



Highlights of recent progress and future challenges in research, prevention, 
control, and education programs include: 

Prevention of There are approximately 1,250,000 heart attacks in America each 
Heart Attacks year. The five major and well-established risk factors for coro- 
-Identification nary artery disease and heart attacks are: age, male sex, high 
0< R|S,< levels of blood lipids, high blood pressure, and cigarette smok- 
3Ct0rs ing. The latter three can be modified, and for two of these we 

know that a decrease in the factor results in reduced risk. Cessa- 
tion of cigarette smoking will decrease the enhanced risk of heart 



11 



attacks among smokers. Reduction of moderate or severe hyper- 
tension reduces devastating complications such as stroke, heart 
failure, and kidney failure. 



Prevention of 
Heart Attacks 
-Modification 

of Risk 

Factors 



The Institute has implemented three large-scale clinical trials 
to evaluate the cardiovascular effects of risk factor modifica- 
tion. Within this decade, we should know the impact of lowering 
the levels of blood lipids on heart attacks and the impact of 
controlling high blood pressure on heart attacks, as well as 
the impact of controlling simultaneously the three major 
risk factors: high levels of blood lipids, high blood pres- 
sure, and cigarette smoking. 



Prevention of 
Heart Attacks 
-Determination 
of Blood Lipids 



Accurate and precise determination of blood lipids is essential 
for effective and efficient risk factor detection and management. 
Review of operating conditions in United States laboratories 
reveals a wide and unacceptable variation in the accuracy and pre- 
cision of blood lipid (cholesterol and triglyceride) measurements. 
Quick-kit methods are totally unacceptable. Many of the large 
automated laboratories are employing techniques that yield values 
10 to 40 percent too high. Over the last two years the NHXI has 
evaluated available technology and developed with industry a rapid, 
inexpensive, accurate, and precise method for determining choles- 
terol and triglyceride levels. 



Prevention of Current studies demonstrate that chronic and asymptomatic dis- 
Heart Attacks orders such as arteriosclerosis (hardening of the arteries) and 
-Behavioral high blood pressure are not easily brought and held under con- 
Studies trol. Health attitudes and lack of motivation often lead to 

failures in compliance with changes in life style or with diets 
and drugs in attempting to change risk factors. Evidence from 
smoking clinics and from diabetics or hypertensives under treat- 
ment indicates that these behavioral elements rather than our 
understanding of risk factors may prove to be the limiting fac- 
tors in our ability to prevent coronary heart disease. 



Prevention of 
Heart Attacks 
-Role of 

Public 

Education 



Public education is of primary importance in the prevention of 
coronary heart disease. Major steps have been taken to educate 
the general public regarding the cai'ses and prevention of coro- 
nary heart disease. An example is the Seattle Heart Watch which 
includes a series of television programs produced with the Uni- 
versity of Washington. Among topics covered in the series are 
dietary alteration, exercise programs, signs of impending heart 
attack, and whom to contact concerning an attack. 



12 



Heart Attacks Epidemiological studies have established strong positive associa- 
-TheRoleof tions with high levels of blood lipids (cholesterol) and with age 
Blood Lipids relative to the incidence of heart attacks. A recent study with 
a special X-ray technique has emphasized these associations in 
terms of the pathological changes in the coronary arteries. 

Heart Attacks A previously undefined syndrome of potentially major clinical 
-A New Sudden importance has been described. This new syndrome has been called 
Cardiac Death the Primary Ventricular Fibrillation Syndrome or Instantaneous 
Syndrome Death Syndrome. Clinically, those patients fortunate enough to 
be resuscitated following sudden collapse exhibit disturbance of 
heart rhythm, absence of recent or evolving myocardial infarction 
(death of heart muscle) , presence of chronic coronary heart disease, 
and a very high incidence of sudden death (30 percent per year) 
subsequent to resuscitation. The recognition of this sudden death 
syndrome presents an opportunity to prevent premature deaths from 
coronary artery disease by preventing or controlling the distur- 
bance in heart rhythm. 



Heart Attacks 
-Therapy to 
Reduce Heart 
Muscle 
Damage 



Recent investigations have shown that the patient's prognosis is 
directly related to the amount of dead heart muscle resulting from 
a heart attack. Pharmaceutical agents, oxygen therapy, and mechan- 
ical circulatory assistance are promising new therapies for limit- 
ing the amount of heart muscle damage from heart attacks. 



High Blood 

Pressure 
-National 
Education 
Program 



Drug therapy to control high blood pressure reduces the incidence 
of strokes and heart failure among persons with moderate or severe 
hypertension. However, only about 12 percent of hypertensives in 
the United States are currently receiving adequate treatment. The 
National High Blood Pressure Education Program, initiated in 1972, 
is an interagency Federal/non-Federal cooperative effort designed 
to bring individuals with moderate and severe hypertension under 
effective treatment. Sustained effective blood pressure management 
in such persons is expected to result in a reduction of disability 
and death by as much as 40 percent when compared with expected rates 
for untreated hypertensives. 



Prevention of 
Heart and 
Blood Vessel 
Disease 

-The Framingham 
Heart Study 



A 22-year follow-up has been completed on 5,209 participants in the 
Framingham study. Analysis of the data reveals that: (1) High blood 
pressure is the major cause of congestive heart failure, with eleva- 
tions of systolic pressure ("upper" blood pressure reading) playing 
as great a role as diastolic pressure ("lower" blood pressure reading) 

(2) Cigarette smoking is a major contributor to intermittent claudi- 
cation (severe cramps and pain in the muscles of the legs on walking 
due to insufficient blood supply) and acts independently of high 
blood pressure, high levels of blood lipids, or diabetic status; 

(3) Obesity is a risk factor in coronary heart disease, stroke, and 
congestive heart failure, independent of other risk factors; and (4) 
The quantitative influence of several risk factors acting simultane- 
ously has been analyzed and the results published for use by clini- 
cians in the prevention of heart disease. 



13 



Understanding Arteriosclerosis is responsible for about 85 percent of the deaths 
Arteriosclerosis from heart and blood vessel diseases. Recent progress has been 
made in the understanding of arteriosclerosis. Certain prelim- 
inary studies of smooth muscle cells that make up the bulk of 
atherosclerotic plaques suggest the possibility that each plaque 
consists mainly of one colony of cells that have all arisen from 
a single cell of the artery wall that is ancestral for the par- 
ticular plaque. While this work remains to be confirmed, it 
raises fundamental issues in the pathogenesis of atherosclerosis. 



Studies of 
the Blood 
Vessel Wall 



While elaborating and extending methods of culturing cells derived 
from human blood vessels, investigators are studying their proper- 
ties to develop ways to use these cells in artificial blood vessels. 
The method has now been carried beyond seven generations of cells 
in culture as pure colonies that maintain all the basic morpholog- 
ical and metabolic properties of the lining of the vessels. These 
methods offer hope for enhancing our ability to construct artificial 
blood vessels compatible with the blood. 



Using 

Computers 
to Detect 
Irregularities 
in the Blood 
Vessel Wall 



Utilizing contrast angiograms (a special X-ray technique) together 
with computerized analysis of the images produced, it has been pos- 
sible to obtain sensitive and highly reproducible diagnosis of 
changes in the blood vessel wall resulting from disease. This 
technique can facilitate early detection of cardiovascular disease. 



Noninvasive Instrumentation is probably the most important single constraint 
Instrumentation to the effective prevention of clinical complications of arterio- 
sclerosis. Convenient, preferably noninvasive, specific, and 
sensitive instrumentation for the diagnosis and monitoring of 
atherosclerotic plaques is needed. This would allow studies of 
the relationship of risk factor levels to actual development of 
arteriosclerosis in the individual patient and provide a precise 
statement of what the total identified risk factors mean for that 
individual. Of most importance, such instrumentation could moni- 
tor the development of arteriosclerosis and measure the therapeutic 
effect of changing one or more of the risk factors. The ability to 
safely determine the results of a therapy or life style change on 
the development of arteriosclerosis, without having to wait for a 
crisis event such as heart attack or death, would also enormously 
decrease the rigorous demands and costs of clinical trials. 



Mechanical 
Circulatory 
Assistance 



Mechanical circulatory assistance with intra-aortic balloon coun- 
terpulsation was introduced into clinical studies about a decade 
ago. Its exact role and effect in patients with acute heart attack 
had to be determined. Studies showed that this form of mechanical 
left heart assist could temporarily reverse shock even when refrac- 
tory to all forms of medical therapy. This assistance permits 
further diagnostic studies and possible surgical therapy in patients 
who would otherwise be unable to withstand these procedures. 



14 



However, the overall impact of this form of therapy remained to 
be determined, especially in relation to the morbidity and mor- 
tality in those patients less critically ill. Recent studies in 
patients have now shown a definite reduction of infarct size asso- 
ciated with the use of mechanical left heart assist. 



Implantable 
Heart Assist 
Device 



A totally implantable left heart assist device may have a signif- 
icant future in terms of acute and chronic cardiac insufficiency. 
In recent experiments, a device has performed successfully in 
calves. In several acute implantations, excellent results were 
obtained in terms of the amount of blood put out by the heart, 
heart rates, and blood pressure. These implantations have demon- 
strated functionally the potential of these devices for individuals 
requiring left ventricular assist. 



HIGHLIGHTS: LUNG DISEASES 



Highlights of recent progress and future challenges in research, prevention, 
trol, and education programs include: 



con- 



Pediatric 
Lung Disease 
-Detection 
Before Birth 



Hyaline membrane disease (HMD) is a disorder of newborn babies 
characterized by the immaturity of the lung. It usually occurs 
in premature infants, starts within hours of birth, and frequently 
leads to death within a few days. Without special treatment, over 
50 percent of babies with this disease will die. If death from 
this disease could be eliminated, the infant mortality rate in 
this country might be reduced to a level comparable to the best 
in the world. Current therapy is available for treatment of 
hyaline membrane disease. However, delay in diagnosis contrib- 
utes greatly to its high morbidity and mortality. A major diag- 
nostic breakthrough has occurred which allows detection of 
hyaline membrane disease before birth. This technique, which 
involves sampling amniotic fluid, promises to result in exciting 
new therapeutic and preventive measures. 



Pediatric Hyaline membrane disease is characterized by collapse of the 

Lung Disease oxygen-exchanging portions of the lung resulting in extreme dif- 
fer* Therapy ficulty in breathing and in death, as noted above. The course 
of HMD is relatively rapid, and survival is usually determined 
within a matter of days to 1 to 2 weeks. Therapeutic efforts 
have focused on methods of maintaining the airways open and 
allowing adequate oxygenation of the blood. Until recently, the 
usual therapy for HMD consisted of artificial ventilation and 
other intensive care usually available in large hospital centers. 
Unfortunately, this was not sufficient. Many infants still died 



15 



from this disease. The therapeutic breakthrough that long has 
eluded investigators may now have been achieved. A provocatively 
simple technique, albeit one that requires scrupulously attentive 
patient care, has resulted in a survival rate of up to 90 percent 
in some studies. This therapy is continuous positive airway pres- 
sure (CPAP) and is used in conjunction with artificial ventilation. 



Asthma 
-Diagnosis in 
the Asymptomatic 
Child 



Asthma, which affects more than 8 million Americans, could be pre- 
vented or treated while still reversible if it were diagnosed suf- 
ficiently early. A diagnostic test has been developed recently 
and is currently undergoing evaluation. This test involves expos- 
ing patients to a substance called methacholine. It may allow 
physicians to predict, perhaps years before symptoms develop, 
whether an individual is a potential victim of asthma. This poten- 
tially important diagnostic tool should permit already available 
therapeutic and preventive measures to be initiated early. 



Chronic Obstructive Chronic bronchitis and emphysema are the major chronic obstructive 
Lung Disease pulmonary diseases (COPD) . A new, and potentially more sensitive, 

-Early Detection method has been developed for early detection of changes in lung 

function and structure which appear to be the first sign of chronic 
obstructive pulmonary disease. This method (measurement of closing 
volume) is now being used on selected populations to determine its 
usefulness as a mass screening test. 

Chronic Obstructive Emphysema is the fastest growing cause of death in the United 
Lung Disease States. There are many different kinds of emphysema, none of 
-Risk Factors which is well understood. Cigarette smoking has long been rec- 
ognized as a major risk factor for emphysema, but attempts to 
identify other causes and risk factors have frequently ended in 
failure. New lines of research have been opened up by the recent 
discovery of a genetic basis for one type of emphysema. Other 
risk factors may soon be found as well. 

Understanding It has been recognized that the lung is an organ with several 
Lung Disease functions which may be as complex as the liver. The structure 
of the lung is also very complex as it is made up of as many as 
40 different cell types. Technology is now at hand to relate 
structure and function at the cellular level by using cell cul- 
ture techniques. As this information develops, it should be 
possible to begin investigations into the molecular basis of lung 
disease — an essential step toward effective prevention and treat- 
ment. 



16 



Artificial Lung 
To Treat 
Respiratory 
Failure 



It has been estimated that at least 150,000 adult patients a year 
suffer from respiratory failure. Despite the availability of 
intensive care units, the lung function of these patients on occa- 
sion continues to deteriorate. Approximately 40 percent of these 
patients die. Therefore, patients with potentially reversible 
lung disorders still die because of a need for short-term respir- 
atory augmentation. An artificial lung has been developed and 
tested that oxygenates the blood external to the body. This 
device can provide long-term (days) support without serious blood 
damage. In recent years, clinical studies have shown that these 
membrane oxygenators can be used successfully to provide partial 
respiratory support for patients with acute respiratory failure. 



HIGHLIGHTS: BLOOD DISEASES AND BLOOD RESOURCES 



Highlights of recent progress and future challenges in research, prevention, 
control, and education programs include: 



Dissolving 
Blood Clots 
in the Lung 



A clinical trial has been completed of an enzyme capable of dis- 
solving blood clots in the lung. Results indicate that the enzyme 
streptokinase (a relatively inexpensive and available preparation) 
dissolves blood clots in the lung just as effectively as the more 
widely publicized urokinase (another enzyme preparation) , which 
is quite difficult to obtain. These results are important to the 
development of more readily available treatment of thromboembolic 
diseases. 



A New Technique 
to Measure 
Abnormal 
Tendency of 
Blood to Clot 



A hypercoagulable state in which the blood is more likely to clot 
than normally contributes to a variety of diseases including devel- 
opment of arteriosclerosis and heart attacks. Methods to ade- 
quately measure or characterize this state have been lacking. A 
method of sufficient sensitivity and specificity has now been devel- 
oped which will make possible earlier initiation of appropriate 
therapy. 



Sickle Cell 

Disease 
-Prevention 
of Sickle 
Cell Crisis 



While clinical trials to evaluate urea as an anti-sickling agent 
have shown that it is not effective in the treatment of the sickle 
crisis, evaluation of other anti-sickling agents continues. Pre- 
liminary studies with sodium cyanate are quite promising. 

A Cooperative Study Group composed of researchers and clinicians 
has been formed to collaborate and work together to answer research 
and clinical questions in sickle cell disease. This group will 
form the nidus for a larger group which will address itself to 
hemolytic diseases in general. 



17 



Five sickle cell disease centers and eleven screening and educa- 
tion clinics have been added to continue research and demonstra- 
tion efforts (bringing the total to 15 centers and 26 clinics) . 



Hemophilia 
-Improved 
Treatment 



A procedure has been developed which will improve production of 
Factor VIII, which is used to stop bleeding in hemophiliac patients. 
This procedure will enable blood banks and laboratories throughout 
the country to obtain more potent and more uniform Factor VIII from 
donor blood. Use of this procedure will improve hemophilia therapy 
and also permit more efficient use of donated blood and plasma. 



Hepatitis 
-Transmission 
through 
Blood 
Transfusion 



Two large studies on the epidemiology of hepatitis B infection 
are nearing completion, including one in New York City of blood 
donors found to be carriers of hepatitis antigen. Newer, more 
sensitive detection systems for hepatitis B are being developed 
and compared. A study of the efficacy of hepatitis B immune 
globulin in the treatment or prevention of hepatitis B infection 
has shown that this agent is not effective in the treatment of 
acute fulminant type B viral hepatitis. 



Preventing the 
Rejection of 
Transplanted 
Organs 



Investigators are pursuing means of preventing the sensitization 
of the transplant patient by lowering or attempting to eliminate 
histocompatibility-antigens (HL-A) in transfused blood. Platelet 
(one of the formed elements in blood) studies are in progress to 
determine the indications for HL-A typing in platelet transfusions. 
Studies of _in vitro methods for removing HL-A from blood will be 
completed this year to be followed by clinical trials on renal 
dialysis patients. 



Development of 
Artificial Materials 
Which Will Not 
Harm Blood 



Important progress has been made in developing techniques to impart 
blood compatibility to materials for artificial organs in contact 
with blood. As one example, a class of "springy" polypropylene 
has been synthesized with unique tissue-like physical properties 
for potential prosthetic applications. The technology now exists 
to graft blood compatible materials, such as hydrogels, to the 
polypropylene surface and thus greatly increase its potential for 
biologic use. 



Safe Materials A method has been developed and evaluated which accurately detects 
for Blood Bags the amount of plasticizer DEHP (di-2-ethylhexylphthalate) , a sub- 
stance leached out of blood bags during blood storage. It should 
now be possible to assess more readily the clinical significance 
of the presence of DEHP in tissues and body fluids of transfused 
patients. 



18 



III. STATUS OF PROGRAM AND UPDATED FIVE-YEAR PLAN 



STATUS OF PROGRAM AND UPDATED FIVE-YEAR PLAN 



The current status of the National Heart and Lung Institute Program and the 
Program Plan over the next five years are presented together in this chapter. 
The overall goals of the National Program are to: promote health, prevent 
disease, treat disease, and restore health. To advance toward these goals the 
Institute, through the National Heart, Blood Vessel, Lung, and Blood Program, 
is focusing primarily on two types of program efforts: 



• Research, and 

• Prevention, Control, and Education. 



The Research programs deal largely with the development of new knowledge and the 
testing and evaluation of existing knowledge. The Prevention, Control, and Edu- 
cation programs deal with the application and dissemination of knowledge already 
developed and evaluated through research, but not yet effectively applied toward 
the prevention, control, and treatment of disease. These Prevention, Control, and 
Education programs are an essential link between biomedical research and health 
care. Their purpose is not to deliver health services but rather to improve and 
expedite the transmission of fundamental research advances to the public and to 
medical practitioners and thereby help to promote the health of our citizens. 

For clarity and emphasis, Research programs and Prevention, Control, and Educa- 
tion programs are discussed separately in this chapter. The Institute gives 
special emphasis to the need for ensuring that the results of research are uti- 
lized for the prevention and control of disease; hence, where appropriate in this 
chapter, Research programs are cross-referenced with Prevention, Control, and Edu- 
cation programs. 

In 1972, the Institute initiated an intensive planning effort in response to the 
National Heart, Blood Vessel, Lung, and Blood Act. This planning effort involved 
the participation of four advisory Panels and their Task Groups drawn from univer- 
sities, medical schools, hospitals, and other institutions throughout the United 
States. Advice and recommendations were also sought from the National Heart and 



19 



Lung Advisory Council, the Interagency Technical Committee on Heart, Blood 
Vessel, Lung, and Blood Diseases and Blood Resources, and representatives of 
non-Federal and voluntary organizations with related programs. Ongoing program 
efforts as well as means for expanding successful past research efforts were 
also considered. 

The purpose of this planning effort was to formulate a National Program for 
heart, blood vessel, lung, and blood diseases and blood resource problems. The 
initial Program Plan developed during this planning effort was published in May 
1973. Since that time, the Institute has carefully reviewed and assessed the 
projects and activities of the National Program. The program structure devel- 
oped initially has been revised (see Table 2, Chapter I). This revised struc- 
ture includes 10 program areas for Heart and Blood Vessel Diseases, 8 for Lung 
Diseases, and 4 for Blood Diseases and Blood Resources. The current status and 
updated 5-year Plan for all of these program areas are presented in this chapter 
in the Research section and the Prevention, Control, and Education section. 

For each program area, the goals, actions, and schedules for implementation, as 
set forth initially, have been reviewed and updated. Recent progress and future 
challenges for each program area have been identified. The results of this review 
are presented here in detail for each program area. Program Goals are correlated 
with Recent Progress and Future Challenges, and specific Actions and Schedules for 
implementation of these Actions are set forth. This comprehensive discussion of 
the National Program should provide the basis for continued monitoring, annual 
review, and updating of the 5-year Program Plan. 



20 



RESEARCH 



Programs of research are fundamental to the National Heart, Blood Vessel, Lung, 
and Blood Program. Future developments in the prevention, treatment, and control 
of disease are dependent upon basic knowledge of the life processes, how and why 
these change with disease, and how such changes might be controlled or reversed. 
For instance, we cannot prevent heart attacks until we know more about the mech- 
anisms of arteriosclerosis, how those mechanisms may be accelerated by risk fac- 
tors, and how the process of arteriosclerosis might be arrested or reversed. Also 
through research, the knowledge necessary for promoting and restoring health will 
be developed. Only when we fully understand, for instance, the normal and abnor- 
mal functioning of the lung will we be able to promote conditions conducive to 
good health. 

The Institute supports a broad range of fundamental and clinical research in order 
to develop this essential information base for achieving the overall goals of the 
National Program. By strongly supporting research, the first and basic step in 
the sequence from acquisition of fundamental knowledge through testing and evalua- 
tion to application of that knowledge, the Institute can provide for the orderly 
progression of activities as conceived in the program strategy cited earlier. 

In this section, research programs are discussed separately for Heart and Blood 
Vessel Diseases, Lung Diseases, and Blood Diseases and Blood Resources. Although 
discussed separately, these diseases are linked one to the other. As stated by 
the Panel Chairmen during the planning effort, "Disordered biological functions 
seldom involve a single area. As examples, pulmonary embolism begins with throm- 
bosis and involves the lung and its circulation as well as the heart. Effective 
delivery of oxygen to the tissue depends on the lung, the heart, the amount, 
type, and functional states of the hemoglobin, and the peripheral circulation." 
Research efforts in one program area will impact on research efforts in other 
program areas. The activities in Coronary Heart Disease will have an impact on 
the program areas of Arrhythmias and Heart Failure and Shock. The recent progress 
and future challenges in research and the scheduled Actions in Cerebrovascular 
Disease are closely related to those for Arteriosclerosis and Hypertension. 
Research advances in understanding Thromboembolic Disorders will be important 
in clarifying the role of these disorders in precipitating heart attacks and 
their relationship to the development of Arteriosclerosis. Developments through 
research on blood compatible prostheses will have an impact on many techniques 
and devices developed for heart, blood vessel, and lung diseases. Research on 
the Structure and Function of the Lung will be important in decreasing the mor- 
tality and morbidity resulting from Emphysema and Chronic Bronchitis. Thus, 
the research programs in all areas are closely related. Appropriately, cross- 
references among the program areas are provided in this Research section to 
elucidate some of the complexities of research. 

In FY 75, the highest priority program areas in research are: Arteriosclerosis, 
Hypertension, Coronary Heart Disease, Structure and Function of the Lung, Emphysema 
and Chronic Bronchitis, Bleeding and Clotting Disorders, Sickle Cell Disease, and 
Blood Resources. These programs are selected as high priority because research 
advances in these areas are expected to have the greatest impact on developing our 
information base on heart, blood vessel, lung, and blood diseases; on preventing 
and controlling these diseases; and on promoting and restoring the health of our 
citizens. 

21 




HEART AND BLOOD VESSEL DISEASES 



The Legislative Act charges the Institute to conduct research programs to 
investigate the epidemiology and etiology of heart and blood vessel diseases, 
and to study the basic biological mechanisms and processes involved in normal 
and abnormal phenomena. An impressive array of opportunities and needs can be 
pursued in the heart and blood vessel (cardiovascular) disease area at this 
time. The approaches that appear most promising, most efficient, and are most 
needed to develop new knowledge about heart and blood vessel diseases are sum- 
marized here. 

Cardiovascular disease is by far our number one health problem in the United 
States. In 1971, an estimated 1,022,000 Americans died from heart and blood 
vessel diseases, i.e., more than 53 percent of deaths from all causes. Of 
these deaths, heart attack was responsible for 676,000, and stroke for 208,000. 
Currently, an estimated 27,710,000 Americans have some major form of heart and 
blood vessel disease; 22,340,000 have hypertension; 3,870,000, coronary heart 
disease; 1,700,000, rheumatic heart disease; and 1,650,000, stroke. 



23 



The Institute planning effort relied heavily on the Heart and Blood Vessel Diseases 
Panel and Task group participants, representing many universities, medical schools, 
hospitals, and other institutions throughout the United States. Advice and recom- 
mendations were also sought from the National Heart and Lung Advisory Council, the 
Interagency Technical Committee on Heart, Blood Vessel, Lung, and Blood Diseases 
and Blood Resources, and representatives of non-Federal and voluntary organizations 
with related programs. The National Program in Heart and Blood Vessel Diseases, 
developed with participation from the above groups, was outlined in the National 
Heart and Lung Institute Summary (Volume I) of the National Heart, Blood Vessel, 
Lung, and Blood Program which was published on May 1, 1973. 

The updated National Program, presented here, represents an assessment and orderly 
expansion of NHLI activities in the cardiovascular area in response to the mandate 
of the National Heart, Blood Vessel, Lung, and Blood Act. The updated heart and 
blood vessel research programs of the National Heart and Lung Institute deal with 
ten program areas: 

1. Arteriosclerosis 

2. Hypertension 

3. Cerebrovascular Disease 

4. Coronary Heart Disease 

5. Peripheral Vascular Diseases 

6. Arrhythmias 

7. Heart Failure and Shock 

8. Congenital and Rheumatic Heart Diseases 

9. Cardiomyopathy and Infections of the Heart 
10. Circulatory Assistance. 

The first nine program areas were identified separately in 1973. The tenth program 
area, Circulatory Assistance, was included initially under the section on Heart 
Failure and Shock, and is presented separately for emphasis in this updated Plan. 

Following its review and evaluation of program activities, the Institute has modi- 
fied some Actions and has increased the total number of research Actions in heart 
and blood vessel diseases from 28 in the initial Plan to 45 in the updated Plan. 
Most of this increase occurs in the program areas of Arteriosclerosis and Coronary 
Heart Disease. These additional Actions will be important in expanding the Insti- 
tute's efforts to prevent heart attacks, the greatest single cause of death in the 
United States. 



24 



1. ARTERIOSCLEROSIS 



PROGRAM 
GOALS 



Arteriosclerosis is by far the most common serious disease affect- 
ing man in Western society. It is responsible for about 85 percent 
of the deaths from heart and blood vessel diseases in the United 
States. It is a slow, progressive disease that sets the stage for 
heart attacks, heart failure, and strokes. To understand the ori- 
gins and control of arteriosclerosis is the primary objective of 
the National Program in heart and blood vessel diseases. 

Recent research has developed a significant amount of new knowledge 
about the causes and development of arteriosclerosis. Significant 
positive statistical associations have been demonstrated between 
arteriosclerotic disease and high blood lipids, high blood pressure, 
heavy consumption of cigarettes, physical inactivity, personality 
type, and other factors. However, we do not yet completely under- 
stand the causal relationship of these variables to arteriosclerosis. 
Current studies on molecular and tissue interactions promise to help 
explain the development of arteriosclerosis and offer opportunities 
for its prevention. 

Obviously, preventing the events leading to atherosclerotic plaque 
formation in the arteries would be better and far less costly than 
attempting to treat the resultant vascular disease and its sequelae. 
The Institute has many leads to prevention and better understanding 
of arteriosclerosis, some of which come from research on metabolism, 
normal and abnormal structure and function of the arteries, and 
genetic and environmental factors which influence atherogenesis . 
The NHLI concurs with the priority recommendations of the Heart and 
Blood Vessel Diseases Panel, which was convened for developing the 
initial plan, to "define more completely the pathogenesis of athero- 
sclerosis" and "to conduct controlled clinical trials." Accordingly, 
the National Program gives high priority to continued emphasis on 
these activities. 



Our overall goal in arteriosclerosis is to obtain a 
better understanding of its basic process and to 
improve the prevention, diagnosis, and treatment of 
the process and its sequelae. 



RECENT 
PROGRESS 



Strong efforts to find solutions to the problem of arteriosclerosis 
are being made in fundamental research, nutritional studies, and 
clinical investigations. As a result of these efforts, the Insti- 
tute can report significant progress in adding new knowledge and 
techniques to help in our attack against arteriosclerosis. Exam- 
ples of these many detailed advances are given below. 



25 



Fundamental Research. The processes leading to the development of 
atherosclerosis are closely related to altered permeability of 
the walls of the arteries. Lipids are deposited in the wall more 
rapidly than they are removed. Experiments in living animals and 
isolated human blood vessels indicate that patterns of increased 
permeability which permit greater fat deposition are virtually 
identical to patterns of early atherosclerosis. The arterial wall 
is made more permeable by various hemodynamic factors such as con- 
strictions, increased blood flow, and increased blood pressure, as 
well as by endothelial injury. 

Studies on the transport of lipids to and from the arterial wall 
have been extended by the development of better techniques of iso- 
topically tagging lipid and protein components of plasma lipopro- 
teins to permit analyses of the mechanism of transport of these 
molecules into the arterial wall, either as units or in parts. 
Methods of determining alterations in "chemical barrier" and wall 
ultrastructure have been developed. Examination of the transport 
of lipid molecules away from the arterial wall once they have been 
deposited indicates this to be a complex and slow process. 

The process of lipolysis (decomposition of lipids) is central to 
the utilization of fats by the body, whether ingested in the diet 
or made in the tissues, and is a major determinant of blood lipid 
concentrations . The part played by various enzymes in the arterial 
wall during this process is being explored. The arterial wall con- 
tains enzymes such as alkaline lipase (lipoprotein lipase) and acid 
hydrolases capable of breaking down the lipids entering the wall 
from the blood. Lipoprotein lipase has been the subject of inten- 
sive study almost continuously since its discovery at the NHLI 
20 years ago. Scientists have now shown that there are at least 
two different lipases that can be liberated into blood to hasten 
lipid removal. One enzyme, coming from the liver, is believed to 
play a role in degrading lipid remnants, possibly for entry into 
the liver. The other acts primarily to degrade larger lipid parti- 
cles, chylomicrons and very low density lipoproteins. Lipoprotein 
lipase is selectively absent in one human mutation (familial Type I 
hyperlipoproteinemia) leading to abnormal levels of lipid in the 
blood of these individuals. Other tissue enzymes capable of decom- 
posing lipids have also been intensively studied this past year. 
New compounds have been found which may be involved in arterio- 
sclerotic plaque formation. The previous observations on the rapid 
and reversible effect of insulin on lipids have been further advanced 
and it is now possible to study more directly the nature of the 
effects of insulin and adrenal hormones in the handling of fats by 
the body. 

Hyperlipidemia (high blood lipids) is one of the major conditions 
associated with premature atherosclerosis, particularly coronary 
artery disease, and is one of the first rank problems facing American 
physicians, especially those engaged in preventive medicine. The 
NHLI has been a leader in promulgating new systems of classification 
and identification of causes and treatment of hyperlipidemia. 

26 



The Institute's extramural Lipid Research Clinic Program had its 
birthplace within the NHLI Intramural Research Division. The prev- 
alence of and mechanisms behind the human forms of hyperlipidemia 
are now being studied at the 12 extramural Lipid Research Clinics 
(LRC's). The 12 clinics are collaborating on a protocol for central 
processing and evaluation of the heart, coronary, and major vessels 
in post-mortem examinations on LRC patients. The central pooling 
and processing of all pathologic material in the LRC Central Pathol- 
ogy Laboratory at the NHLI will allow us to gather useful clinical 
pathologic correlations regarding human hyperlipidemias . 

In several of the Institute's Specialized Centers of Research in 
Arteriosclerosis, improvements are now being made in invasive and 
noninvasive diagnostic methods for the recognition of atherosclero- 
tic plaques in the blood vessels. Other fundamental studies involve 
the development and use of nonhuman primate models for studies on 
the development, progression, and regression of the atherosclerotic 
process. 

Nutrition. Nutritional factors are believed to play an important role 
in the development of arteriosclerosis, and studies are in progress 
to clarify the role of these factors. The Multiple Risk Factor Inter- 
vention Trial, currently being implemented, has a strong nutritional 
component with the objective of reducing elevated serum cholesterol 
by adherence to a lipid-lowering diet, and in certain cases, weight 
control and correction of obesity. In addition, reduced intake of 
total carbohydrate and alcohol will be advised for men with elevated 
triglycerides who fail to respond to the basic diet. 

A detailed nutritional questionnaire and 1-day diet recall are 
included in the Lipid Research Clinics' prevalence studies, and a 
central computerized data system has been created to evaluate the 
role of diet in hyperlipidemia and the association of diet with the 
incidence of vascular disease. The relationship of nutritional fac- 
tors to lipid metabolism and development of atherosclerosis is being 
studied by many scientists, primarily in the Institute's Specialized 
Centers of Research in Arteriosclerosis. 



Clinical Investigations. The clinical investigations within the program on 
arteriosclerosis are varied, complex, and broad in scope. The recent 
progress highlighted here only refers to some of the major efforts 
underway and does not, by far, reflect the total Institute effort. 
The Lipid Research Clinics are initiating an in-depth study of the 
relatives of patients found to have primary hyperlipoproteinemia 
during the prevalence studies. The clinics are also finalizing a 
protocol to evaluate the feasibility of using placental cord blood 
for the early diagnosis of hyperlipidemia. A central clinical chem- 
istry laboratory has been selected for the network of clinics collab- 
orating in the Lipid Research Clinics Primary Prevention Trial, 
designed to test whether or not lipid lowering can prevent or delay 
the onset of manifest vascular disease. Recruitment of patients for 
this important clinical trial has begun. 



27 



The planning and organizational phases for another primary preven- 
tion trial, the Multiple Risk Factor Intervention Trial, have just 
been completed. Twenty clinics, a coordinating center, and a cen- 
tral EKG and chemistry laboratory for the trial have been selected. 

Two extensive studies of patients with the most common form of 
hypercholesterolemia (hyperbetalipoproteinemia. Type II hyperlipo- 
proteinemia) were completed in 1973 by the NHLI's Intramural Research 
laboratories . One study involved analysis of over 200 children born 
of parents with a form of familial hypercholesterolemia, which prob- 
ably affects about 1 in 200 Americans . The genetic data indicated 
a clear-cut mode of inheritance determined by a single gene and mani- 
fested early in childhood; information about the clinical manifesta- 
tions and potential for diagnosis at birth was also developed. In 
a companion analysis, the cardiovascular risks of this hypercho- 
lesterolemia in over 1,000 relatives of affected patients were exam- 
ined. This was the most extensive such analysis ever undertaken of 
this genetic defect. This study provides striking evidence of the 
premature atherosclerotic risk of patients affected with this disorder. 

In-depth genetic investigation of risk factors is being encouraged 
in the Specialized Centers of Research in Arteriosclerosis. A study 
is in progress to characterize with regard to cardiovascular risk 
factors the familial and genetic associations of offspring of 1,644 
spouse sets who were part of the original Framingham cohort. More 
than 2,200 offspring have undergone evaluation to date in this study. 
The NHLI Twin Study has now collected data on more than 600 sets of 
identical twins aged 25 to 55, and preliminary results indicate major 
genetic determinants of the observed variability in height, weight, 
blood pressure, and serum cholesterol. Offspring study of the pro- 
positi of the Honolulu cohort of the Honolulu-Hiroshima-San Francisco 
Heart Disease Study has also begun. 

The Coronary Drug Project, a secondary prevention clinical trial of 
lipid-altering drugs has reached an average follow-up of 58 months 
in a population of 8,400 men aged 30 to 64 who have had one or more 
myocardial infarctions prior to entry into the study. This trial 
has already uncovered unfavorable features of two drugs, i.e., 
estrogen and dextro thyroxine, and is scheduled to terminate in 18 
months . 



future All aspects of the study and treatment of arteriosclerosis would be 
challenges greatly advanced if we had diagnostic instruments for detecting 

small changes in atherosclerotic plaques. The present state of tech- 
nological development suggests that this is possible. Current 
approaches include highly sophisticated techniques such as ultrasonic 
methods, X-ray densitometry, and computer-assisted enhancement of 
complex image signals. These techniques are not yet adequate but 
indicate a feasible and promising technical area where rapid and 
successful progress can be expected. 



28 



Many needed studies of chronic arterial disease cannot be conducted 
in man and require the development of suitable animal models of human 
disease, particularly nonhuman primate models with chronic experimen- 
tal arteriosclerosis and chronic experimental hypertension. These 
models would allow us to study the development and regression of 
atherosclerotic plaques, local biochemical and cellular changes in 
advanced plaques, and treatment of advanced plaques. Animals with 
spontaneous metabolic disease such as hyperbetalipoproteinemia (ele- 
vated blood lipids) or diabetes need to be bred to create resource 
colonies for studies of the relationship of these disorders to arte- 
riosclerosis. 

Recent studies have shown genetic influence on the metabolism of 
lipoproteins, on the excretion of sterols, and on the atherogenetic 
reaction of the arterial wall. This research, presently incomplete 
and in need of both confirmation and detailed investigation, will be 
fundamental to the identification of patients at high risk of arte- 
riosclerosis as well as to the development of rational treatment. 

A strong, general research program is needed in the pathogenesis of 
arteriosclerosis with emphasis on studies of lipoproteins and their 
interaction with the vessel wall. Recent progress in cellular 
research, enzyme studies, and collagen and mucopolysaccharide chemis- 
try now allows sophisticated investigation of the tissue in the 
artery wall and its role in plaque formation. In addition, current 
population studies such as those in the Institute's Lipid Research 
Clinics and Specialized Centers of Research in Arteriosclerosis 
have identified a need for new and sophisticated investigations to 
clarify the role of nutrition in the development and treatment of 
arteriosclerosis. 

Several clinical trials are currently underway to evaluate ways of 
preventing coronary heart disease. These efforts are aimed at inves- 
tigating the potential benefits derived from controlling the risk 
factors of high blood lipids, high blood pressure, and smoking. 
Potentially useful drugs and surgical approaches are under study. 
Such important trials of potential preventive measures have both 
theoretical and practical value. 

Arteriosclerosis takes years to become clinically evident. In the 
interval, the individual may appear to be in good health. Often 
the first evidence is catastrophic illness such as heart attack or 
stroke. Therefore, if we are to reach the patient before it is too 
late, efforts must be made to reach the patient in the community 
with the latest information through programs in health education, 
public motivation, and compliance with preventive or therapeutic 
regimens. (See section on Prevention, Control, and Education.) 



29 



actions The Institute plans to: 



1. Emphasize pathogenetic studies within existing research programs, 
centers of research, and lipid research clinics. 

2. Stimulate development of sensitive, specific, invasive and non- 
invasive, convenient, and safe diagnostic techniques for use in 
determining arteriosclerotic changes in blood vessels. 

3. Evaluate current techniques for diagnosis of hyperlipoprotein- 
emia and other risk factors and encourage the development of 
better ones. 

4. Establish colonies of suitable animal models with particular 
reference to nonhuman primates with arteriosclerotic or hyper- 
tensive disease for use in research on arteriosclerosis, hyper- 
tension, and cerebral vascular disease. Animal research will 
also be encouraged in genetics related to arteriosclerosis. 

5. Expand current population studies in the Institute's Lipid 
Research Clinics, Specialized Centers of Research in Arterio- 
sclerosis, and clinical applications and prevention programs to 
include in-depth genetic studies. 

6. Encourage experts in psychology, sociology, and behavioral 
research to investigate the problems associated with health 
education and attitudes, motivation, and compliance as these 
relate to the prevention of arteriosclerosis, hypertension, or 
stroke and to the therapy and rehabilitation of patients with 
these diseases. (See section on Prevention, Control, and Educa- 
tion. ) 

7. Implement a Multiple Risk Factor Intervention Trial to determine 
whether, for men at above average risk of death from coronary 
heart disease (because of elevated serum cholesterol, elevated 
diastolic blood pressure, and cigarette smoking) , a special inter- 
vention program will result in a significant reduction in mortal- 
ity from coronary heart disease. 

8. Continue an intervention study in high-risk subjects to test the 
effectiveness of lowering the concentration of lipids by selected 
means to reduce cardiovascular mortality and morbidity. 

9. Provide for acquisition, analysis, and storage of data on the 
prevalence of different types of hyperlipoproteinemia, particu- 
larly in young age groups, with special emphasis on their rela- 
tionship to diet and premature atherosclerosis. 



30 



10. Promote further clinical, laboratory, and epidemiologic studies 
of personal attributes and life styles such as nutrition, exer- 
cise, obesity, cigarette smoking, behavior, biochemical and 
hormonal patterns, and response to psychosocial stress and their 
relationship to the development of arteriosclerosis, coronary 
heart disease, stroke, and hypertension, particularly with respect 
to the onset of arteriosclerosis in the young and in women. 

11. Expand current population studies and develop new epidemiologic 
studies of the role of environmental factors such as trace sub- 
stances, water hardness, climate, geography, and occupational 
exposures in the pathogenesis of arteriosclerosis. 

12. Implement the US-USSR cooperative study to define the prevalence 
of different types of hyperlipoproteinemia, their relationship 
to environmental factors, especially nutrition, as well as many 
broadly defined cardiovascular risk factors. 

schedule The costs of clinical trials now in progress will plateau in FY 75. 
Present programs related to the prevalence of lipid abnormalities 
and hypertension among children and young and middle-aged adults will 
be completed between FY 76 and FY 78. Program action will be contin- 
ued or initiated in pathogenesis, instrumentation, epidemiology, 
genetics, nutrition, animal models, and behavioral studies. 



2. HYPERTENSION 

program High blood pressure is a leading cause of disease and death in the 
G0ALS United States, particularly among the black population. It is a 

major risk factor in coronary heart disease. One of every six adults 
has some elevation of blood pressure. High blood pressure can be 
controlled, and we know that such control results in a reduced inci- 
dence of stroke and heart failure, kidney failure, and perhaps also 
a reduced incidence of heart attacks. 

In more than 90 percent of the cases, the cause of the hypertension 
is unknown, and although the condition can be treated, it cannot be 
cured or prevented. Because of the large numbers of people affected 
by hypertension and its serious nature, it would be especially desir- 
able to be able to prevent it; to accomplish this, increased emphasis 
is needed in fundamental research. 



• The long-range goal in hypertension is to prevent it; 
the short-range goal is to optimize the utilization 
of effective treatment which currently exists. 



31 



recent Research related to high blood pressure is a major effort within 
progress the Institute's program on heart and blood vessel diseases. The 
regulation of normal blood pressure is dependent upon striking a 
balance between a number of vasodilator and vasoconstrictor systems. 
Therefore, studies have been undertaken in each of these systems to 
identify their roles in hypertensive disease and also to define the 
interrelationships between them. 

Kallikreins are enzymes which control the production of certain sub- 
stances, kinins, which are potent endogenous vasodilators (agents 
that dilate blood vessels) . Normal volunteers excrete on the aver- 
age twice as much kallikrein in the urine as patients with essential 
hypertension. These patients appear to have reduced basal activity 
of the kallikrein-kinin system and also reduced responsiveness to 
physiologic stimuli. 

The renin-angiotensin-aldosterone system is vasoconstrictor. During 
the past year radioimmunoassay procedures have been developed which 
are easier, quicker to perform, and very specific, sensitive, and 
reproducible. Normal levels of plasma renin activity (PRA) have been 
established and it has been shown that urinary and plasma kallikrein 
levels can be dissociated from PRA. It has also been demonstrated 
that a centrally acting antihypertensive drug, alphamethyldopa, is 
capable of lowering PRA. 

The prostaglandins (PG) are endogenous unsaturated fatty acids with 
potent effects on blood vessels. A radioimmunoassay has been devel- 
oped which makes it possible to measure very small amounts of these 
substances in the plasma or urine. 

Catecholamines and the adrenergic nervous system have profound 
effects on blood pressure and renal function. Studies show that 
acute infusions or chronic administration of salt to normal humans 
cause an increase in a urinary substance, dopamine; a decrease in 
another substance, norepinephrine; and a decrease in a blood enzyme, 
dopamine (3-hydroxylase. This enzyme plays a key role in the mainte- 
nance of the salt and water balance of the body. 

Blood pressure, like most physiologic variables, is a periodic func- 
tion. Studies on the classification, causes, and/or the treatment 
of hypertension are in progress, including a detailed study of the 
rhythm for blood pressure and the characterization of the circadian 
component. The ultimate objective is to define an optimal treatment 
for each patient with special reference to the abnormalities of con- 
trolling factors shown by that patient. 

In the past year, unusual success has been achieved in the develop- 
ment of assays needed to carry out the complex biochemical studies 
needed for the investigation of factors relative to hypertension. 
Specialized laboratories are working on various assays of angiotensins, 
aldosterone, and prostaglandins to determine more fully the role of 
each in the pathogenesis and etiology of hypertension. In 1973, 
clinical tests were started of an agent which blocks the conversion 

32 



of Angiotensin I to Angiotensin II. Since Angiotensin I is inac- 
tive on blood vessels while Angiotensin II is an effective constric- 
tor, it will be possible to measure the effect on blood pressure when 
one effector is eliminated. If this test proves to be as useful as 
anticipated, more laboratories will be encouraged to use it in their 
studies. 

Epidemiological data will be forthcoming from the Hypertension Detec- 
tion and Follow-up Program (HDFP) which began its operational phase 
in February 1973. Population data from 14 communities will become 
available to characterize prevalence of hypertension by a limited 
number of demographic, socioeconomic, and occupational characteris- 
tics. Follow-up of the 5,000 participants in the Regular Care Group 
will provide general population data on the progression of high blood 
pressure and its complications. An important component of the Hyper- 
tension Detection and Follow-up Program involves behavioral research 
as it relates to the identification of factors which enhance adher- 
ence to therapy or impede such adherence among individuals placed 
on antihypertensive drug management. 

Data on high blood pressure are now available from six prospective 
epidemiological studies in populations which have had follow-up 
observations and blood pressure measurements over 4 to 18 years. 
Systematic analysis of these data is underway. Data from Puerto 
Rican, Israeli, Yugoslavian, Honolulu Japanese American, and 
Hiroshima Japanese populations are available to compare with the 
present 18-year follow-up data from Framingham. 

An increasing number of projects deal with the role of stress in 
the genesis of hypertension. A pilot clinical trial of antihyper- 
tensive therapy in mild hypertension is being planned. This trial, 
jointly supported with the Veterans Administration (VA) , is pro- 
posed for initiation in four VA hospitals. 

An intensive study of the pharmacokinetic actions of antihyperten- 
sive drugs is underway. Combinations of available drugs are being 
tested in individual patients. It appears possible that therapy 
may soon be tailored to the functional aberrations found in an indi- 
vidual hypertensive subject. 

future We do not know how beneficial treatment may be for mild forms of 
challenges high blood pressure. Since an estimated 19 million people have 

mild hypertension, it is important that this information be devel- 
oped. About 4 million people at any given time have hypertension 
of a degree known to be harmful. It can be controlled by medica- 
tion with appropriate drugs. However, currently available drugs 
require close medical supervision and often have unpleasant side 
effects which make them difficult to use for long periods of time 
in asymptomatic individuals. We need to develop better pharmaco- 
logic agents without such side effects and without the need for 
meticulous, individually adjusted dosage. 



33 



Behavioral and motivational considerations similar to those men- 
tioned under Arteriosclerosis are particularly important to the 
successful maintenance of antihypertensive therapy, since patients 
with high blood pressure seldom have characteristic symptoms until 
catastrophic complications occur. Rational treatment and preven- 
tion of hypertension will require an intensive investigation of its 
etiology and pathogenesis. While some current information about 
the formation and modulation of vasopressor polypeptides and related 
enzyme systems helps to explain pathogenetic mechanisms, we know 
little about etiology. 

Dissemination of information about high blood pressure and the bene- 
fits of treatment represents a major challenge discussed in the 
section on Prevention, Control, and Education. 



ACTIONS 



The Institute plans to: 



1. Emphasize research on the etiology and pathogenesis of hyper- 
tension, including its epidemiology, in many of the individual 
and specialized laboratories working on this problem. 

2. Implement clinical trials of antihypertensive therapy in mild 
and labile hypertension. 

3. Evaluate new pharmacologic approaches to the treatment of hyper- 
tension utilizing existing research centers and pharmacologic 
expertise, with emphasis on new drug formulations. 

schedule Present programs will continue to receive emphasis. The prevalence 
studies of hypertension in children will be completed as mentioned 
in the section on Arteriosclerosis. Continuing and new actions will 
increase somewhat in FY 75 and increase further by FY 79. Part 
of this increase is attributable to the proposed clinical trial of 
therapy for mild hypertension. Additional increases will occur in 
the pathogenesis and pharmacology of hypertension. 



3. CEREBROVASCULAR DISEASE 



PROGRAM 
GOALS 



Cerebrovascular disease due to arteriosclerosis and especially due 
to hypertension is the basis for the great majority of strokes. 
An estimated 1.7 million adults in the United States have this dis- 
ease, and of this number, about 200,000 persons will die of stroke 
each year. While the National Institute of Neurological Diseases 
and Stroke is primarily responsible for programs on those aspects 
of stroke that deal with brain injury and its consequences, the NHLI 
is responsible for programs on the cerebrovascular pathology that 
underlies the stroke. 



The goal of the NHLI program is to decrease the 
incidence of stroke through studies of the pathology 
and pathogenesis of cerebrovascular disease. 



34 



recent A liaison Joint Council Subcommittee has been drawn from the 
progress Advisory Councils of the National Institute of Neurological Dis- 
eases and Stroke and the National Heart and Lung Institute, and 
other appropriate experts and Institute staffs for the purpose of 
coordinating and exchanging information on cerebrovascular diseases. 
During the past several years, this Subcommittee has served as a 
focus for information exchange, development of bibliographies, con- 
ferences and workshops and similar activities related to the National 
Program in cerebrovascular disease. 

Currently within the National Program, only a small number of primar- 
ily human studies are concerned with the cerebral vasculature and its 
relationship to stroke. A few animal studies are concerned with the 
effects of hypertension on vessels, but do not relate primarily to 
the cerebral vessels. The experimental modeling of the vascular 
pathology of stroke in animals is a largely inactive research area 
for investigators in arteriosclerosis and has had only limited inves- 
tigation in hypertensive models. There are no current studies of 
the combined effects of arteriosclerosis and hypertension on the 
cerebral blood vessels. 



future To determine the etiology and prevention of stroke, we need to con- 
Challenges duct animal studies of the effects of chronic arteriosclerosis and 

chronic hypertension on the arteries of the brain. Little knowledge 
is available as yet about chronic changes in animal models, partic- 
ularly in nonhuman primates appropriate for neurological examination. 
The goals of these animal studies will be to elucidate, by methods 
not applicable to man, the vascular pathology that leads to stroke. 
Insofar as cerebrovascular disease is closely related to arterio- 
sclerosis and hypertension, the future challenges discussed in the 
sections on Arteriosclerosis and Hypertension also apply to Cerebro- 
vascular Disease. 



ACTIONS 



The Institute plans to: 



1. Initiate studies in animals of the pathology of the lesions of 
chronic atherosclerosis and hypertension in the cerebrovascular 
arteries. Emphasis will be placed on those lesions that may 
contribute to ischemic stroke or arterial brain hemorrhage. The 
chronic and special animal resources referred to in the sections 
on Arteriosclerosis and Hypertension can be utilized with minor 
expansion or redirection for the study of cerebrovascular disease. 

2. Continue prospective epidemiologic studies dealing with the 
identification of environmental factors and personal attributes 
which predispose to increased risks of stroke; maintain surveil- 
lance of stroke end-points in the clinical trials discussed in 
the sections on Arteriosclerosis and Hypertension. 

schedule The planned actions in animal studies and clinical research will 
gradually increase the current program effort in the cerebrovas- 
cular area through FY 79. 



35 



4. CORONARY HEART DISEASE 

program Coronary heart disease is the major manifestation of atheroscle- 
goals rosis. It is the predominant form of heart disease in the adult 

American, causing 1.25 million heart attacks a year and responsible 
for chronic illness in 4 million Americans, 2.5 million below the 
age of 65. 

Of the five major and well-established risk factors for coronary 
artery disease, namely age, male sex, high blood lipids, high 
blood pressure and cigarette smoking, the latter three can be modi- 
fied, and two of these are known to result in reduced cardiovascu- 
lar risk when deliberately decreased. Cessation of cigarette smok- 
ing will decrease the enhanced risk of heart attacks among smokers, 
and reduction of moderate or severe hypertension reduces stroke and 
some other complications of high blood pressure. Its effect on 
heart attack or sudden cardiac death is unknown but may be appre- 
ciable. The Institute has implemented three large-scale trials to 
evaluate the cardiovascular effects of risk factor modification. 
These are described in the previous sections on Arteriosclerosis 
and Hypertension. 

A research program focused on patients with acute heart attacks 
has developed extensive information about pathophysiology; prog- 
gnostic factors; pharmacological, surgical, and circulatory assist 
therapy; and techniques and instruments for conducting research in 
the acutely ill patient. These developments can now be built upon 
and more broadly used. 



A primary goal of the program is to develop informa- 
tion that will lead to improved diagnosis, prevention, 
therapy, rehabilitation, and understanding of the 
mechanisms resulting in symptomatic coronary disease. 



Coronary artery bypass surgery has been developed to supplement 
medical management of coronary heart disease, particularly in the 
case of angina pectoris. This technique uses a blood vessel graft 
to bypass a narrowed or occluded segment of a coronary artery. 
Over 25,000 such operations are done annually in the United States 
with hospitalization costs in excess of $5,000 for each operation. 



• A second goal is to establish the indications for and 
the effects of coronary artery surgery in the treat- 
ment of various forms of coronary heart disease. 



36 



Each year about 400,000 deaths from coronary heart disease occur 
before hospitalization, half of these almost instantaneously or 
unwitnessed. Over three-quarters of these victims have known 
heart disease or high blood pressure before their sudden deaths, 
but in the rest, sudden cardiac death is the first evidence of 
heart disease. 

• A third goal is to develop and assess emergency med- 
ical care methods for heart attack victims and to 
develop and evaluate prophylactic treatment with 
drugs to prevent sudden cardiac death. 

Following heart attack or other manifestation of heart disease, 
tens of thousands of Americans annually are left with substantial 
impairment of their ability and freedom to function and to con- 
tribute fully to society. 

• A fourth major goal of the program is to assess the 
needs and opportunities for cardiac rehabilitation 
with respect to physical, physiological, and societal 
factors to prevent disability and to bring back into 
the mainstream of life those who have suffered cardio- 
vascular disease. 

In addition to topics identified under Coronary Heart Disease, 
closely related work is included in the sections on Arteriosclero- 
sis, Arrhythmias, Heart Failure and Shock, and in the section on 
Prevention, Control, and Education. 

recent In 1972 and 1973, the Institute implemented three large-scale clin- 
progress ical trials, as described in the sections on Arteriosclerosis and 

Hypertension, directed toward evaluating the cardiovascular effects 
of risk factor modification. After two to five years of planning, 
the Hypertension Detection and Follow-Up Program, Lipid Research 
Clinic, and Multiple Risk Factor Intervention trials have begun 
patient recruitment. Within this decade, we should know the impact 
of lowering lipids on heart attack in certain types of lipid dis- 
orders, the impact of controlling hypertension on heart attack, as 
well as the impact of controlling simultaneously the three major 
risk factors. 

Plans for Specialized Centers to conduct research on the various 
manifestations of coronary heart disease have been developed. Phase 
I of the Collaborative National Study on Coronary Artery Surgery is 
completed. The US-USSR Cooperative Study on Management of Ischemic 
Heart Disease is moving forward on schedule. The results of present 
studies on mechanisms and factors precipitating acute cardiovascular 
events and their prodromata are being evaluated. Pilot testing of 
antiarrhythmic drugs to be given to patients following hospitaliza- 
tion for acute myocardial infarction is progressing satisfactorily. 

37 



Studies for early administration of prophylactic antiarrhythmic 
drugs in the emergency care settings have begun but are proceeding 
slowly. A task force has been established to assess the needs and 
opportunities for the physiological, psychological, and societal 
rehabilitation of patients with cardiovascular disease. 

Scientific research in the past has resulted in the current treat- 
ment of heart attack, specifically relief of pain and prevention 
or reversal of rhythm disturbances which can be lethal. Recent 
investigations (more fully described in the section on Heart Fail- 
ure and Shock) have shown that the size of the infarct (the amount 
of dead heart muscle) is directly related to death or disability 
from a heart attack. Studies are currently underway to develop 
better ways to assess infarct size as well as to assess therapies 
for limiting the size of infarcts. For example, for many years, 
physicians have administered oxygen to patients with heart attack, 
although firm scientific evidence for its usefulness has not existed. 
Recent animal experiments show that inhalation of oxygen decreases 
the extent of damage to heart muscle. This suggests that there is 
indeed rationale for its continued use in patients. The use of a 
pump to assist the heart in patients with heart attack has been 
shown to relieve pain, and if applied early in the course of the 
attack, limits the amount of heart muscle destroyed. In combina- 
tion with certain drugs, the effect is even more striking. 

future The emphasis in patient-oriented research must shift from its cur- 
challenges rent focus upon acute heart attack to the inclusion of other impor- 
tant aspects of coronary heart disease — angina pectoris, heart fail- 
ure, arrhythmias, and sudden death. Attention must be paid to further 
development and evaluation of therapy, rehabilitation, and measurement 
techniques. The fundamental question of why chronic coronary artery 
disease is finally manifested as acute heart disease — heart attack 
or sudden death — must be answered. These research areas have been 
emphasized by the National Heart and Lung Advisory Council. The 
study of susceptible patients requires specialized facilities that 
are complex, expensive, and staffed with personnel who are available 
for emergencies. Importantly, such specialized cardiological facil- 
ities will be very useful for research on other forms of heart dis- 
ease as well. 

It is widely recognized that coronary artery surgery brings relief 
of symptoms for a majority of patients with severe angina pectoris. 
However, the benefits and side effects, the value compared to con- 
ventional drug therapy, and the effects upon lifespan and quality 
of life require further research. 

Recent studies have shown that the final step in sudden cardiac 
death is usually ventricular fibrillation, which is largely prevent- 
able during hospitalization by drugs given intravenously. Thus, 
finding drugs to prevent ventricular fibrillation in high risk 
patients is an important research task, and agents must be found 
that can be used immediately upon the development of heart attack 
symptoms . 

38 



The high frequency of out-of-hospital deaths and the favorable 
experience with improved systems of emergency cardiac care under- 
score the need for further development of emergency-related tech- 
niques and resources for use in cardiac patients. A strengthened 
scientific basis for rehabilitation programs and a more comprehen- 
sive scope of action for these programs are needed. Development 
and testing of new hypotheses and methods are critical to continued 
clinical and fundamental research into the cause, diagnosis, and 
treatment of coronary heart disease. 



actions The Institute plans to: 



1. Establish approximately 12 specialized units to conduct research 
upon the various manifestations of coronary heart disease. Com- 
prehensive clinical investigation will be supported by related, 
fundamental laboratory studies. 

2. Establish a collaborative national program to determine the indi- 
cations for and the long-term effects of coronary artery surgery 
in the management of coronary heart disease. Randomized studies 
will be utilized in patients with sharply defined clinical con- 
ditions and coronary arterial involvement. A registry will be 
used to follow patients in whom the indications for surgery or 
exclusively medical treatment seem sufficiently clear that ran- 
domized allocation would be improper, but in whom follow-up 
clinical data are important for assessing the validity of present 
clinical judgments. 

3. Implement the US-USSR cooperative study on the management of 
ischemic heart disease by medical and surgical techniques. 

4. Promote studies to elucidate the mechanisms and factors which 
precipitate acute coronary events and to determine the charac- 
teristics of individuals at highest risk for these events. 

5. Promote studies on the prodromata of acute coronary events and 
of patients' reactions and coping behavior in this setting with 
a view toward earlier diagnosis and treatment. 

6. Develop and test techniques of emergency cardiovascular diag- 
nosis and therapy suitable for incorporation into emergency 
medical care systems . 

7. Design, pilot test, and subsequently implement large-scale 
trials of chronically administered antiarrhythmic drugs in 
patients at high risk for sudden cardiac death. 

8. Implement the US-USSR cooperative study on the prevention of 
sudden cardiac death. 



39 



9. Design, pilot test, and subsequently implement large-scale 

trials of the early administration of prophylactic antiarrhythmic 
drugs immediately upon the development of heart attack symptoms. 

10. Assess the needs and opportunities for cardiac rehabilitation 
in terms of physical, psychological, and societal factors, 
and implement appropriate programs of research. 



schedule The present long-term study of lipid-lowering drugs aimed at pre- 
venting recurrence of heart attack or death from coronary heart 
disease (the "Coronary Drug Study") is being completed in FY 74 and 
will be terminated by FY 75. The Myocardial Infarction Research 
Units, which have focused upon heart attacks, will be discontinued 
by FY 75. Continuing and new actions in coronary heart disease will 
emphasize manifestations other than heart attack, particularly 
angina pectoris and sudden cardiac death. In part, this will be 
accomplished through the development of specialized units. The 
emphasis will shift toward electrophysiological and surgical inves- 
tigations, with specific attention to prevention of acute events. 



5. PERIPHERAL VASCULAR DISEASES 



PROGRAM 
GOALS 



Peripheral vascular diseases are the cause of considerable suffering 
and disability. Surgeons have developed techniques to replace dis- 
eased peripheral artery segments with vascular or prosthetic grafts. 
Otherwise, peripheral arterial disease has been the focus of only a 
limited research effort, and peripheral venous disease and disorders 
of the lymphatics have received even less emphasis. 



• The goals of this program are to improve diagnosis, 
therapy, and rehabilitation, and to improve under- 
standing of the mechanisms causing peripheral arterial, 
venous, and lymphatic diseases. 



RECENT 
PROGRESS 



Some epidemiological data on the prevalence, incidence, and poten- 
tiality of risk factors are being obtained from prospective popu- 
lation studies. The bulk of developments related to Peripheral 
Vascular Diseases is described in the section on Arteriosclerosis. 



FUTURE 
CHALLENGES 



Methods must be developed for diagnosing peripheral vascular dis- 
eases before they reach an advanced state, for more effective 
medical management, and for extending surgical therapy to small 
vessels. Understanding the basic cause of the diseases is most 
important and will require study of the role of neural control of 
vascular tone, mechanism of action of smooth muscle, pathogenesis 
of peripheral atherosclerosis, and the importance and significance 
of risk factors. 



40 



actions The Institute plans to: 



Encourage clinical, laboratory, and epidemiological research 
into the causes, diagnosis, and treatment of diseases of the 
peripheral arteries, veins, and lymphatics. 

Implement related programs described in the section on Arterio- 
sclerosis, and the programs on noninvasive instrumentation dis- 
cussed in the section on Bleeding and Clotting Disorders under 
Blood Diseases and Blood Resources. 



schedule Continuing and new Actions in peripheral vascular diseases will 
emphasize clinical and basic investigation. Emphasis will be on 
diagnostic techniques for small vessels, and the relation of phys- 
iology and pathophysiology to clinical manifestations of disease. 
Multidisciplinary approaches will be emphasized as well as specific 
approaches . 



6. ARRHYTHMIAS 

program Important new concepts are developing about the correlation of 
GO ALS electrical signals from the heart and the extent, severity, and 

prognosis of heart disease. Information is being accumulated about 
the different causations of arrhythmias and their differential 
responses to drug therapy. Most of the drugs currently effective 
in the treatment and control of arrhythmias have side effects which 
limit their applicability. 



• A major goal of the program is to develop methods for 
the prevention of arrhythmias which specifically cause 
sudden cardiac death. 



Identification of arrhythmias that carry a high risk of sudden 
cardiac death is fundamental to preventive measures and has been 
emphasized by the National Heart and Lung Advisory Council. The 
analysis of spontaneous rhythms and the influence of drugs must be 
assessed by quantitative analysis of extensive electrocardiographic 
tape recordings. Substantial progress has been made toward per- 
forming this task automatically, rapidly, and quantitatively by 
computer . 

Arrhythmias and other electrical disturbances of the heart cause 
important symptoms and aggravate many forms of heart disease. 

• Another goal of the program is to improve currently 
available methods for prevention, diagnosis, and 
management of arrhythmias and other electrical dis- 
turbances of the heart. 



41 



recent Clinical studies are in progress to identify chronic or intermit- 
progress tent disturbances of rhythm, and several projects are primarily 
directed at the electrophysiology and therapy of rhythm disturb- 
ances associated with inadequate blood supply to the heart. A 
collaborative study is being developed to describe significant 
arrhythmias in specific groups of patients and their modification 
by drug therapy. Improved automated arrhythmia analysis of electro- 
cardiographic records is being achieved. 

A previously undefined syndrome of potentially major clinical 
importance has recently been described. This new syndrome is called 
the Primary Ventricular Fibrillation Syndrome or the Instantaneous 
Death Syndrome. Clinically, those patients fortunate enough to be 
resuscitated following their sudden collapse exhibit disturbance 
of heart rhythm, absence of recent or evolving myocardial infarction, 
chronic coronary artery disease, and a very high incidence of sudden 
death (at 30 percent per year) subsequent to resuscitation. Patho- 
logically, from medical examiners' series, the syndrome is charac- 
terized by severe chronic coronary artery disease, absence of recent 
coronary artery lesions, and no evidence of recent myocardial 
necrosis. 

This syndrome, which may comprise up to 50 percent of all cases of 
sudden cardiac death, can be differentiated from other cases of 
sudden cardiac death which have been characterized clinically by 
ventricular fibrillation, a high incidence of premonitory symptoms, 
recent or evolving acute myocardial infarction, and a lower occur- 
rence of subsequent sudden death (at 2 percent per year) . The 
recognition of this new syndrome presents a challenge for preventing 
premature death from coronary artery disease. 

future A better understanding of the electrical behavior of ischemic 
challenges heart muscle is essential to the prevention of sudden cardiac death. 
Several drugs which are effective agents in the setting of the coro- 
nary care unit need to be evaluated for benefits and side effects 
as prophylactic agents outside the hospital in patients suspected 
of having myocardial infarction. Particular attention needs to be 
paid to the effect of heart rate upon automaticity and rhythm dis- 
turbances as well as upon the work load and consequent potential 
damage to the heart. Antiarrhythmic drugs, which can be taken 
orally over long periods of time, and which have shown promise in 
limited clinical trials, need to be evaluated in larger-scale trials. 
Fundamental to all these clinical studies is the development of 
systems for quantifying electrocardiographic rhythm signals auto- 
matically and rapidly. In addition to the efforts focused upon 
ventricular fibrillation and the prevention of sudden cardiac death, 
disturbances of the conduction system of the heart, as well as other 
important rhythm disturbances, must be managed more effectively. 
Closely related topics are also discussed under the section on 
Coronary Heart Disease. 



42 



ACTIONS 



The Institute plans to: 



1. Expand current programs for the prevention of arrhythmias 
causing sudden cardiac death, focusing particularly upon the 
electrophysiology and therapy of rhythm disturbances associated 
with inadequate blood supply to heart muscle and upon clinical 
studies to identify chronic or intermittent disturbances of 
heart rhythm which indicate an increased risk for sudden death. 

2. Augment the development of automated, quantitative techniques 
for analyzing electrocardiographic rhythm signals to facilitate 
clinical investigation of arrhythmias. 



schedule it is anticipated that the current major emphasis on descriptive 
aspects of conduction disturbances will be somewhat diminished. 
Continuing and new Actions related to arrhythmias will emphasize 
those fundamental to understanding sudden cardiac death. There 
will be an overall expansion of program activity with a peak in 
currently projected programs in FY 78 and FY 79, and subsequent 
levelling off of activity by FY 80. 



7. HEART FAILURE AND SHOCK 

program Heart failure and shock may be the end result of many different 
GOALS diseases. The National Heart and Lung Advisory Council has given 
priority to studies of heart failure. In a heart attack, blood 
supply to a part of the heart muscle becomes so severely reduced 
that the muscle undergoes irreversible damage. It can no longer 
contract or pump and is ultimately replaced by a scar. The amount 
of irreversibly damaged muscle is not predetermined at the onset 
of the heart attack; there is a zone which is in jeopardy but has 
not yet progressed to the point of no return. Current research has 
identified several promising means for protecting this zone of 
potentially reversible damage and for promoting its recovery. Some 
of these approaches are being investigated in initial clinical feasi- 
bility trials; other promising techniques are being tested in animal 
studies . 



A major goal is to minimize heart failure associated 
with and following heart attack by enhancing the sur- 
vival of damaged heart muscle. 



Methods to quantify the amount of heart muscle which is inadequately 
perfused or which has undergone irreversible damage are crucial to 
the evaluation of therapeutic interventions. Recently, several such 



43 



methods have shown promise. They may make it possible to test new 
approaches more economically and in fewer patients than is now 
required for evaluation by gross clinical criteria. 



• A second goal is to develop more satisfactory means 
of quantifying the extent of heart muscle which is 
inadequately perfused with arterial blood or which 
has undergone irreversible damage. 



Other aspects of the diagnosis, etiology, therapy, and prevention 
of heart failure and shock warrant emphasis. These include research 
on improving the pumping function of heart muscle, as well as under- 
standing and treating the disturbances of the regulation of periph- 
eral blood vessels, the related endocrine functions of the body, and 
the functioning of the kidney. 



• A third goal of the program is to improve understanding 
and management of heart failure and shock due to cardio- 
vascular causes. 



recent The biochemical and physiological studies fundamental to the sur- 
progress vival of heart muscle and to the development of methods to prevent 
heart muscle damage are continuing. Pilot studies with a variety 
of therapeutic agents are underway and some show considerable thera- 
peutic promise. Examples of such agents are cited in the section on 
Coronary Heart Disease. Progress is also being made in radioiso- 
topic quantification of heart muscle which is underperfused or 
damaged. 

future Current therapy to enhance the survival of ischemic heart muscle 
challenges must be evaluated on a larger scale by more definitive clinical 
studies than those now underway. The effects upon infarct size 
must be quantified and survival assessed. Ischemic heart muscle 
must be studied at the cellular and subcellular levels, in an 
effort to develop more effective therapy. 

The techniques for quantifying the degree of heart muscle damage 
must be validated. Subsequent use of the best techniques would min- 
imize the number of patients needed for evaluation of new modes of 
therapy. Electrocardiographic, enzymatic, and radioisotope tech- 
niques show promise. 

Studies of heart failure and shock need to be expanded to include 
other organ systems. Thus, as the National Heart and Lung Advisory 
Council has recommended, the dynamics and the neural and endocrine 
control of the circulation must be studied in the periphery as well 
as in the heart, kidney, and other organs. 



44 



actions The Institute plans to: 



1. Enlarge biochemical and physiological studies of the fundamen- 
tal processes associated with heart muscle survival both in 
laboratory and clinical studies. Based upon these studies, 
develop methods for minimizing the extent of heart muscle dam- 
age in a heart attack. 

2. Establish clinical studies, contingent upon success of current 
pilot studies, to assess the therapeutic efficacy of promising 
techniques for minimizing the extent of heart muscle damage. 

3. Expand the program for quantifying the extent of heart muscle 
which is inadequately perfused or which has undergone irrevers- 
ible damage. 

4. Implement the US-USSR cooperative program on myocardial metab- 
olism. 



schedule Continuing and new Actions related to cardiac failure and shock 
will emphasize the pathophysiology of ischemic myocardium and 
methods of quantifying this condition, as well as directing atten- 
tion to systemic responses to heart failure and shock. Clinical 
trials will be ready for phase-in in FY 75 and FY 76; a number of 
promising techniques have progressed to a stage where they are ready 
for clinical evaluation on a moderate scale. These new efforts were 
initiated in FY 74. The program will peak in FY 79, and begin to 
level off by FY 80. 



8. CONGENITAL AND RHEUMATIC HEART DISEASES 

program Congenital and rheumatic heart diseases are important disorders of 
goals childhood, and may form the basis for considerable impairment of 
the quality of life of the patient surviving into adulthood. 

The earliest surgical successes in the treatment of heart diseases 
were in the correction or palliation of congenital heart disease. 
These successes are being expanded in the development of diagnostic 
and surgical techniques applicable to the newborn. Important in- 
sights have also been gained into the development of the cardio- 
vascular system. However, in most cases, science still does not 
know what makes the heart develop abnormally before a baby is born. 

• The major goals of the program are to understand better 
the causes of congenital heart disease, to improve diag- 
nosis and therapy, and to rehabilitate patients with 
congenital heart disease, particularly the newborn. 



45 



Rheumatic heart disease is an immunological disturbance that fre- 
quently occurs years after initial rheumatic fever and prior 
streptococcal infection. It can not only shorten life, but also 
seriously impair the quality of the patient's life. Improved 
understanding and control of immunological problems could thus be 
important in the identification of susceptibility and the preven- 
tion of rheumatic heart disease, as well as in the success of 
cardiac transplants and in the prevention or treatment of cardio- 
myopathy and possibly other forms of heart disease. 



• Another important goal is to attain a better under- 
standing of the immunological problems associated 
with heart diseases. 



Closely related programs are discussed in the section on Prevention, 
Control, and Education, and deal with the management of congenital 
heart diseases in the newborn. 



recent The Institute has maintained a continuing long-term effort focused 
progress upon all facets of the problems of congenital and rheumatic heart 
disease, resulting in a steady improvement in the clinical manage- 
ment of these patients. Extremely delicate operations that were 
inconceivable a few decades ago are now performed routinely in most 
of the major medical centers. It is now possible to perform very 
complex repair of the heart even in young infants. 

future Essential to the prevention of congenital heart disease is a better 
challenges understanding of the normal development of the cardiovascular 

system and the causes of abnormal development. The National Heart 
and Lung Advisory Council has recommended that the Institute con- 
duct an "intensive interdisciplinary study of all aspects of the 
etiology and pathophysiology of congenital heart disease and the 
neonatal cardiovascular system." The roles of maternal infection 
and toxic exposures during pregnancy are particularly relevant. 
The emphasis on diagnosis, therapy, and rehabilitation of congen- 
ital heart disease patients must increasingly involve the newborn, 
as well as school age children. Particular attention must be paid 
to measures that will "assure the first few hours of life." 
Research challenges in the management of congenital heart d:'. eases 
in the newborn are closely related to programs discussed further 
in the section on Prevention, Control, and Education. 

The roles and nature of immune mecha: » ;ms as they relate to the 
heart need to be better understood. Therapy for the suppression 
of harmful immunological responses must be developed and evaluated. 

Both clinical and fundamental research on causes, diagnosis, and 
therapy of congenital heart disease, rheumatic ^ever, and rheumatic 
heart disease must be continued with periodic updating of approaches. 

46 



ACTIONS 



The Institute plans to: 



1. Establish Specialized Centers of Research in Congenital Heart 
Disease at two to four locations in FY 76. The research in 
these Centers will emphasize such topics as cardiovascular 
development and improved diagnostic techniques and therapy, 
particularly in the newborn. 

2. Establish a targeted effort to study immunological problems in 
heart disease and their management, specifically in relation 

to rheumatic heart disease, cardiac transplantation, and cardio- 
myopathies. 

3. Implement the US-USSR cooperative study on congenital heart 
disease. 



schedule There will be a diminished emphasis on the hemodynamic and surgical 
aspects of these diseases in older children and adults. The con- 
tinuing and new actions will emphasize the causes of both congenital 
and rheumatic heart diseases . In coordination with the National 
Institute of Child Health and Human Development, the National Heart 
and Lung Institute will give special attention to the role of infec- 
tions, drugs, and other toxic exposures during pregnancy in congen- 
ital heart disease. For congenital heart disease, there will be 
an increasing clinical emphasis on the neonatal period. 



9. CARDIOMYOPATHY AND INFECTIONS OF THE HEART 

program Cardiomyopathy and infections of the heart, which are diseases of 

goals the heart muscle and its lining, cause enlargement of the heart, 

heart failure, irregularities of heart rhythms, and occasionally 

sudden death. The prevalence of these diseases, caused by a 
variety of factors, is unknown. 



The goals of the program are to prevent, diagnose, 
and treat the various cardiomyopathies and infec- 
tions of the heart, with particular emphasis on 
improved understanding of their causes. 



recent New ways of studying these diseases have been developed. Cardio- 
progress myopathies and infections of the heart are being recognized with 
increasing frequency. The importance of toxic substances, viral 
infections, and immunological phenomena is widely recognized, 
although a number of causes remain unknown. Accordingly, the 
National Program is giving priority to identification of the eti- 
ologies of cardiomyopathy. The advent of antibiotics has substan- 
tially diminished heart disease caused by bacterial infections. 
However, new problems have arisen, such as infections on pros- 
thetic heart valves. 



47 



future There is particular need to understand the causes of cardiomy- 
CHALLENGES opathies and myocarditis. Cellular and subcellular biochemical 
and immunological studies offer opportunities for improving our 
understanding of these problems. The roles of toxic substances, 
including drugs and alcohol, and of viral infections and genetic 
disorders need to be investigated. Better diagnostic and thera- 
peutic approaches to these diseases must be developed. Since 
these diseases stem from a variety of causes, research efforts 
need to be broadly based and involve multiple disciplines. 



ACTIONS 



The Institute plans to: 



1. Focus attention on studies of the etiologies of cardiomyopathies 
and infections of the heart, emphasizing epidemiological methods, 
viral and immunological research, the development and utiliza- 
tion of animal models, and the determinations of mechanisms 
of myocardial damage by application of biochemical, physio- 
logical, physical, and pharmacological techniques. (See also 
Congenital and Rheumatic Heart Diseases, Action #2 on immuno- 
logical problems.) 



schedule Continuing and new actions, with initial emphasis on causation, 
will permit increase in activity as this unresearched field is 
developed, with progressive increases in funding through FY 80. 



10. CIRCULATORY ASSISTANCE 

program Present and foreseeable techniques of general and pharmacological 
goals management of acute and chronic cardiac insufficiency and shock 

still leave a substantial fraction of patients with compromised or 
fatally impaired heart function. By mechanical supportive means, 
it is possible to substitute some of the pumping function of the 
heart and to relieve its work load. Presently, such techniques 
are possible briefly in man and for longer periods in the experi- 
mental animal. 



• A major goal of the program is to develop and assess 
therapeutically effective, safe, and reliable cardiac 
assist and total replacement heart devices for support- 
ing or taking over the work load of the heart. 



Methods for assessing and quantifying the degree of circulatory 
impairment are also necessary to evaluate patients with all forms 
of suspect or known heart disease and particularly for patients 
with heart failure and shock. 



48 



• A second goal is to develop the instrumentation and 
techniques for the assessment of cardiovascular per- 
formance . 

recent Partial and totally implantable left ventricular assist devices 
progress may be significant in the future in terms of correcting acute and 
chronic cardiac insufficiency. In recent experiments, a left ven- 
tricular assist device has performed successfully in vivo in calves. 
In ten acute implantations, excellent results were obtained in 
terms of cardiac output, heart rate, and blood pressure. 

Left ventricular assist with intra-aortic balloon counterpulsation 
was introduced into clinical studies about a decade ago. Studies 
showed that this form of mechanical assist could temporarily 
reverse shock in subjects refractory to all forms of medical therapy, 
permitting additional diagnostic and therapeutic procedures. Addi- 
tionally, in a small group of patients with severe refractory shock, 
an occasional life could be salvaged. However, the overall impact 
of this form of therapy in patients with acute myocardial infarction 
remained to be determined, especially in relation to the morbidity 
and mortality in those patients less critically ill. Recent patient 
studies have now shown a definite reduction of infarct size associ- 
ated with the use of this mechanical device. This reduction of 
infarct size, which previously could only be demonstrated in animal 
studies, may represent a promising method to decrease subsequent 
patient morbidity and mortality. 

future Mechanical techniques for augmenting or substituting for the per- 
CHALlenges formance of the heart must be expanded to encompass emergency 

temporary devices for short-term management, extracorporeal assist 
pumps for intermediate periods of use, long-term implanted heart 
assist devices, and total cardiac replacements. An associated 
opportunity and need exist for research on the physiology of assisted 
circulation, as well as on the development of the requisite compo- 
nents of the systems — compatible biomaterials , pumps, actuators, 
energy transforming devices, implantable energy systems, transcu- 
taneous transmission of energy, and the control system for the 
devices. 

Plans for the future include chronic in_ vivo assist experiments in 
calves, followed potentially by clinical application in man for 
short-term left-heart bypass support. Eventually, longer-term 
implantation in man for the purpose of supporting or totally 
replacing a weakened heart may result. 

These types of studies with mechanical circulatory assist are very 
promising, and further work is now clearly indicated. Smaller 
infarct size has been associated with a better patient prognosis, 
but the effect of reducing infarct size on prognosis has not been 
definitely proven. Finally, the subgroup of acute myocardial 
infarction patients who might benefit most from this relatively 
invasive type of procedure must be determined before this inter- 
vention is widely recommended. 



49 



actions The Institute plans to: 

1. Continue the research, development, and assessment of emergency 
temporary, circulatory support devices directed at short-term 
management of heart failure and shock to stabilize the clinical 
condition and permit its reversal. 

2. Expand the research, development, and assessment of implantable 
heart assist devices capable of taking over a significant frac- 
tion of the work of the heart for extended periods of time. 

3. Undertake research, development, and assessment of external 
heart assist devices capable of taking over a significant frac- 
tion of the work of the heart, and requiring minimal surgery 
for connection and removal. 

4. Expand research, development, and assessment of implantable 
heart replacement devices for permanent implantation. 

5. Expand research and development upon circulatory assist and 
artificial heart systems, including the development of com- 
patible biomaterials , appropriate pumps, actuators, energy 
transforming devices, implantable energy systems, transcutane- 
ous transmission of energy, and control systems for the devices. 

6. Expand research and development of noninvasive and invasive 
instruments and techniques for the assessment of cardiovascular 
performance. 

schedule Present programs in the development of circulatory assist devices 
will continue. An assessment will be made of long-range goals to 
include the relative needs and opportunities for the development 
of devices which offer substantial clinical benefit, yet fall short 
of the most ambitious goals of totally implantable and permanently 
energized long-term cardiac assist or replacement. 

The selective termination of targeted activities as their objectives 
are met will be outweighed by the need for larger-scale reliability 
and performance tests prior to and with the advent of substantial 
long-term clinical implants. 



50 




LUNG DISEASES 



The National Heart, Blood Vessel, Lung, and Blood Act encourages the Institute 
to place greater emphasis on lung diseases in the National Program. 

Lung Diseases covered by the Program account for an estimated 150,000 deaths each 
year in the United States, cause 60 million days lost from work, 40 million days 
of bed-restricted activity, and cost the economy about $6 billion a year in lost 
productivity and wages and medical care costs. 

In 1972, the National Heart and Lung Institute convened a task force to assist 
in identifying high-priority problems and approaches for immediate and long- 
range plans to expand the attack on lung diseases in our country. In this effort, 
188 scientists assessed the magnitude of respiratory disease problems in the U.S., 
reviewed available knowledge on the causes of respiratory diseases and the methods 
for diagnosis and treatment; pointed to disparities between current efforts and 
needs in controlling these diseases; and recommended ways to strengthen present 
research programs. 



51 



The task force report became a primary resource document for the Lung Diseases 
Panel, convened in the fall of 1972 in response to the legislation. The recom- 
mendations of this Panel were reviewed by the Institute, the National Heart 
and Lung Advisory Council, and the Interagency Technical Committee, and formed 
the basis for developing the Institute's expanded program on lung diseases, as 
well as for developing the plans for coordination of the overall National Pro- 
gram in Lung Diseases. 

The initial lung program has been reviewed and updated by the Institute during 
the past eight months. The updated National Program is presented here and repre- 
sents an assessment and orderly expansion of NHLI activities in respiratory dis- 
eases. The Program continues to be responsive to the Legislative Act, which 
encourages special attention to childhood diseases and chronic lung diseases, 
including the establishment of National Research and Demonstration Centers. 
The Institute's program, which addresses immediate as well as long-range objec- 
tives, centers on three specific approaches of comparable importance and urgency: 



Research on the structure and function of the lung in order to 
gain fundamental information which will improve our understanding 
of important factors in the promotion of health and the preven- 
tion and treatment of lung diseases. 

Expansion and development of our knowledge base on specific 
diseases which constitute national health problems, but which 
represent areas where current information is insufficient to 
provide immediate solutions. 

Application of available technical resources to solve specific 
problems whose solutions are expected to pay immediate divi- 
dends in improving the health of our nation. 



The updated program goals, recent progress, future challenges, actions, and 
schedules for implementation are discussed below for each program area: 



1. Structure and Function of the Lung 

2. Pediatric Pulmonary Diseases 

3. Emphysema and Chronic Bronchitis 

4. Fibrotic and Immunologic Lung Diseases 

5. Respiratory Failure 

6. Pulmonary Vascular Diseases 

7. Inhalation Diseases 

8. Respiratory Assistance. 



52 



The first five program areas are continuations of those outlined in the initial 
Plan. The last three areas have been added this year and given increased empha- 
sis in the updated lung diseases program. The Institute's revised Plan incor- 
porates most of the Actions set forth in the initial Plan without change or only 
slight revision. Seven new research Actions have been added this year for the 
three new program areas. The respiratory diseases addressed by the Institute 
do not include cancer of the lung, which is the concern of the National Cancer 
Institute, nor upper respiratory infections or pulmonary tuberculosis, which 
are the concern of the National Institute of Allergy and Infectious Diseases, 
and, in certain cases, of the Center for Disease Control. 



1. STRUCTURE AND FUNCTION OF THE LUNG 

program Our current capability to deal with the problems of lung disease 
goals i n the United States is severely limited by our lack of fundamental 
knowledge about the lung. This knowledge must be gained before 
truly definitive preventive and therapeutic measures can be designed. 
Current remedies are not only very costly but are also only tempo- 
rary, stopgap techniques which need to be replaced by more specific 
and longer-term methods yet to be discovered through research. 
Thus, the most important priority now in the Institute's lung dis- 
eases program is to expand research on the lung and its biology in 
order to identify factors critical to the health of the lungs. 
Recent progress in basic scientific disciplines, such as molecular 
biology, biochemistry, immunology, and ultrastructural anatomy 
offer new opportunities for making major advances toward combating 
emphysema, chronic bronchitis, pulmonary fibrosis, asthma, pediatric 
pulmonary diseases, respiratory failure, pulmonary vascular dis- 
eases, and inhalation diseases. 



While it is essential to first focus studies on the 
cellular biology of the normal lung, the ultimate 
goals of the program are to increase understanding 
of the disease processes and develop effective methods 
for prevention, diagnosis, and therapy of lung dis- 
eases. 



RECENT 
PROGRESS 



Recently, a major step has been taken toward an understanding of 
lung disease mechanisms. The lung — an organ with numerous functions 
that include gas exchange, defense against diseases, and removal of 
inhaled substances such as dust — is made up of about 40 different 
types of cells. Recent progress in studies at the cellular level 
has contributed to understanding relationships between lung struc- 
ture and function. Studies have advanced to the point that it 
should be possible to describe the multiple functions of the various 
types of lung cells in terms of cellular and biochemical changes 
associated with different respiratory diseases. 



53 



However, before such abnormalities can be understood, it is neces- 
sary to have a firmer knowledge of normal lung cell structure and 
function. This is a difficult research task because of the multi- 
functional nature of the lung and because of the various roles 
performed by different lung cells. Unless the different types of 
lung cells can be isolated and studied separately, the changes 
associated with various disease states will be impossible to pin- 
point. Recently, an enzymatic procedure has been developed for 
dispersing lung tissue into separate viable cells, thereby providing 
an opportunity to isolate and culture individual cell populations 
from whole lung tissue. 

The major advantage of using cell culture techniques is that large 
quantities of a single cell type can be accumulated and readily 
used in experiments. Once techniques are developed to culture 
single cell types, the specialized requirements for cell growth may 
be examined, and ultimately a comparison made of cells grown from 
normal individuals and those from individuals with specific lung 
diseases. 
i 

future The next several years of research activity will provide infor- 
challenges mation relating structural and biochemical characteristics of 

individual lung cells. As this information develops, investiga- 
tions into the molecular basis of lung disease should be possible. 
This is an essential step toward effective prevention and treat- 
ment. 
i 

Specific opportunities and needs for the future include studies of 
the quantities, composition, and mechanisms of development of var- 
ious components in normal lung tissues, and their chemical precur- 
sors and possible variations with age, sex, and environmental influ- 
ences. Structural proteins, lipids, and hormones may be involved 
in diffuse pulmonary fibrosis and in various types of obstructive 
disease of the airways. The in_ vivo balance and interaction among 
proteolytic enzymes and their potential for altering the connective 
tissue in the lungs need to be elucidated. The turnover rates of 
lung cells and alterations in these rates with disease require fur- 
ther study. 

Failure of the lung's defense mechanisms may play an important 
part in disease processes. The structure, synthesis, and physico- 
chemical properties of bronchial mucus, one of these defense mech- 
anisms, need to be investigated. The cilia in the bronchial tree 
are another vital defense mechanism. Information on their struc- 
ture and function is crucial to understanding lung clearance and 
host defense. 



54 



Some classical areas of pulmonary physiology require continued 
study and correlation with new knowledge of cellular biology, struc- 
ture, and function. Physiologic studies will continue to develop 
information on the mechanical properties of the lungs and the pul- 
monary blood vessels, and the coupling of mechanical events to the 
neurophysio logical regulation of ventilation. 



ACTIONS 



The Institute plans to: 



1. Encourage investigator-initiated research in metabolism, cellu- 
lar biology, and defense mechanisms of the lung. This will be 
supplemented as needed by targeted research addressed to topics 
not adequately covered by investigator-initiated research. 

2. Develop multidisciplinary approaches, such as program projects 
or Specialized Centers of Research, in the area of normal lung 
structure and function. In addition, we will initiate new types 
of targeted programs for collaboration and exchange of informa- 
tion between basic scientists such as biochemists, immunologists, 
and cell biologists, who are not yet focusing on the lung, and 
pulmonary specialists who need to develop information in basic 
science areas. 

3. Seek new information on the structural components of the lung. 
Encourage studies on the alterations in proteins and cells 
associated with dissolution of lung tissue as a consequence of 
injury. 



schedule New research programs in lung cell separation and culture are being 
encouraged. A program on the separation and characterization of 
lung elastin is being developed. Synthetic inhibitors for the 
enzyme elastase will be prepared and distributed to the research 
community. A workshop will be sponsored to encourage research on 
metabolic functions of the lung. Programs which are not included 
in the planned priority actions relating to structure and function 
of the lung will not be further developed. Continuing and new 
actions in pulmonary structure and function will be divided between 
multidisciplinary and specific approaches with gradually increasing 
activity through FY 79. 



2. PEDIATRIC PULMONARY DISEASES 



PROGRAM 
GOALS 



Among childhood disorders involving the lung, cystic fibrosis, and 
hyaline membrane disease are health problems of national signifi- 
cance. Respiratory distress syndrome (hyaline membrane disease) 
is the most common cause of death in the newborn in the United 
States, and affects between 50,000 and 100,000 babies each year, 



55 



about half of whom die. Bronchiolitis, also covered in the National 
Program, is one of the major obstructive airway diseases of children 
and may be important in the development of adult chronic lung dis- 
ease. The cause of respiratory distress syndrome of the newborn, 
the nature of cystic fibrosis, and the possible long-term effects 
of early childhood bronchiolitis need to be determined and under- 
stood. 



• Until research has uncovered ways to prevent hyaline 
membrane disease, early diagnosis and prompt initi- 
ation of therapy are essential to save the lives of 
babies born with this disorder. Primary goals of this 
program are to develop improved methods for early diag- 
nosis and to design more effective modes of therapy. 

• Similarly, present modes of therapy for cystic fibrosis, 
a genetically determined disease, are at best palliative. 
The primary goal at this time is to develop a rational 
basis for therapy through an understanding of the patho- 
genesis of this disease. 

• There is reason to believe that bronchiolitis in chil- 
dren may be related to chronic lung disease in the adult. 
Therefore, an important goal is to conduct long-term, 
follow-up epidemiologic studies of children who have 

had bronchiolitis. 



recent Two important breakthroughs have occurred in the detection and 
progress treatment of hyaline membrane disease. First, it is now possible 
to detect the disease before birth. Secondly, an important thera- 
peutic breakthrough has occurred which dramatically reduces the 
mortality from this dreaded disease. 

The novel and provocative diagnostic technique involves sampling 
amniotic fluid (amniocentesis) and promises to result in exciting 
new therapeutic and preventive measures. Surfactant material is 
produced and secreted by the fetal lung into the amniotic fluid. 
Thus, the surfactant levels in amniotic fluid reflect the fetal 
lung's ability to produce and secrete surfactant. A rapid and 
easy test of surfactant in amniotic fluid has been developed, and 
studies are underway to improve the accuracy of the diagnosis. 
The ability to predict hyaline membrane disease in the fetus per- 
mits the earliest possible medical care for the newborn child and 
opens up new avenues of approach to this disorder by detecting 
prematurity of the infant and preventing immaturity of the lung. 

Survival of infants with hyaline membrane disease is usually deter- 
mined within a matter of days to 1 to 2 weeks. Therapeutic efforts 
have focused on methods of keeping the airways patent and main- 
taining adequate oxygenation of the blood through artificial venti- 
lation and other aspects of intensive care usually available in 



56 



large hospital centers. Unfortunately, this was not sufficient 
and more than half of these infants died. A provocatively simple 
technique, albeit one that requires scrupulously attentive patient 
care, has resulted in survival of up to 90 percent of these babies. 
This therapy, known as continuous positive airway pressure (CPAP) , 
is used in conjunction with artificial ventilation. CPAP keeps 
the lungs expanded and the oxygen exchanging portions open and 
functioning. Thus, the blood is readily oxygenated and the baby's 
overtaxed heart is relieved. CPAP still requires further study 
since it may result in circulatory alterations and possibly adverse 
effects on the airways. However, many of these problems can be 
overcome through application of available intensive care techniques. 
With increasing acceptance of this exciting therapeutic achievement 
by neonatal intensive care units throughout the country, the mortal- 
ity due to this disease should be drastically reduced. 

A conference has been held which explored the clinical aspects of 
cystic fibrosis and its treatment as well as the underlying genetic 
and physiologic alterations. Although this disease affects many 
organs, the pulmonary impairment which may be related to recurrent 
infections and abnormalities in mucus production commonly causes 
disability or death. The Institute's program is addressed to eval- 
uation of cardiac and pulmonary functions and their alteration with 
therapy. The biochemistry of the mucus abnormality is also being 
investigated, and a meeting has been held to exchange information 
and stimulate new approaches in the study of mucin. 

Several groups are engaged in research on methods for early diag- 
nosis of airway disease in newborns and young children. A spi- 
rometer designed for compliance measurements in premature and term 
newborn infants is in the developmental stage. A system which is 
designed to measure pressure-volume curves of the lung and thorax, 
and functional residual capacity in anesthetized subjects is also 
being evaluated. Investigators have initiated a long-term study 
of effects of viral lower respiratory tract illness in children on 
later development of adult lung disease. Serum alpha-1-antitrypsin 
(an enzyme) activity and serum antibody titers to common respira- 
tory viruses are being measured in children with bronchiolitis. 

future Understanding the biochemistry and molecular biology of surfactant 
challenges during normal maturation and hyaline membrane disease in order to 
develop methods of modifying or preventing the disease is a major 
challenge. Therapy for hyaline membrane disease should be improved 
by development of new devices and approaches and ways to initiate 
treatment as soon as possible. The efficacy of present methods of 
treatment needs to be assessed and knowledge about such methods 
widely disseminated. A better understanding of the etiology and 
pathogenesis of hyaline membrane disease is expected with new 
methods of prevention and improved therapy. 



57 



The cause of the mucus abnormalities in cystic fibrosis and the 
pulmonary derangements which result must be discovered before 
effective and meaningful therapeutic and preventive measures can 
be undertaken. 

As a first step in determining whether bronchiolitis in childhood 
predisposes to chronic lung disease in the adult, criteria for 
diagnosis of bronchiolitis and protocols for long-term study need 
to be established. 



actions The Institute plans to: 

1. Extend interdisciplinary studies of biochemical changes associ- 
ated with hyaline membrane disease through Specialized Centers 
of Research. In addition, programs will be initiated to study 
biochemical changes associated with the development of cystic 
fibrosis. 

2. Test various supportive measures for patients with cystic 
fibrosis, including mist-tent therapy and bronchodilators . 

3. Improve management and therapy of hyaline membrane disease 
through the development of programs for rapid transfer of 
infants with this disease to intensive care units. Programs 
will be initiated for research and development of new or 
improved devices for treatment and controlled clinical trials 
of available methods of treating hyaline membrane disease and 
cystic fibrosis. 

4. Initiate epidemiologic studies to determine prospectively the 
long-term effects of bronchiolitis in childhood on the occur- 
rence of chronic lung disease in the adult. 

schedule Because recent findings hold great promise for an effective thera- 
peutic approach to hyaline membrane disease, and because of 
increasing awareness of the importance of the pulmonary manifesta- 
tions of cystic fibrosis to morbidity and mortality from this 
childhood disease, the programs in pediatric pulmonary diseases 
will be increased beginning in FY 75 and maintained at a level 
that includes modest increments until FY 79, when a levelling off 
will occur. Since early initiation of treatment of hyaline mem- 
brane disease is essential for infant survival, the NHLI will 
initiate early in FY 75 plans for a program of recognition and 
early treatment of neonatal respiratory insufficiency and respira- 
tory failure. During this period, there will be a phase-in and 
gradual expansion of the education program, described in the sec- 
tion on Prevention, Control, and Education. 



58 



3. EMPHYSEMA AND CHRONIC BRONCHITIS 

program Chronic obstructive pulmonary disease (COPD) is a major health 
GOALS problem in this country. Each year, direct and indirect costs of 
COPD amount to approximately $1.8 billion and 90,000 man-years of 
lost productivity. Emphysema and chronic bronchitis are the two 
main diseases which, when considered together, are referred to as 
COPD. Both emphysema and chronic bronchitis produce breathlessness, 
cough, and increased susceptibility to respiratory failure and 
death. COPD attacks middle-aged men and women and is particularly 
common in smokers. It is now believed that early abnormalities 
(physiologic and biochemical) related to emphysema and chronic 
bronchitis may be detected at a stage when lung damage is still 
reversible. 



Because of the nature of these disease problems, a 
goal of the program is to prevent development of 
these diseases by early diagnosis and identifica- 
tion and control of risk factors. 

At the same time, because of the great number of 
individuals suffering from already established and 
progressive disease, another goal is to improve 
treatment and rehabilitation programs. 

To understand the mechanisms and causes of these 
diseases is also an important goal and will be 
greatly aided by the development of basic knowledge 
of normal lung biochemistry, metabolism, response 
to injury, and repair processes. (See the section 
on Structure and Function of the Lung.) 



recent Emphysema is the fastest growing cause of death in the United 
progress States and is now the third leading cause of death from respira- 
tory disease. The NHLI is currently placing major emphasis on 
efforts to identify the risk factors of COPD. There are many 
different kinds of emphysema, none well understood. Cigarette 
smoking has long been recognized as a major risk factor for emphy- 
sema, but attempts to identify other causes and risk factors have 
often ended in failure. New lines of research have opened up 
through the recent discovery of a genetic basis for one type of 
emphysema. Environmental risk factors are being identified in a 
variety of occupations. 

A genetic enzyme defect known as alpha- 1-anti trypsin deficiency 
has recently been identified as a factor in the development of 
emphysema. When inherited from both parents, this enzyme defect 
has been shown to be associated with the development of a severe 
form of familial emphysema which attacks young adults. This 



59 



emphysema is rapidly progressive, resulting in death by the early 
40 's — a time of peak earning potential and productivity. It is 
not known for sure whether individuals with only one gene for the 
defect (i.e., inherited from only one parent) are also at higher 
risk, but early results indicate that at least one group of such 
carriers may be at particularly high risk. 

Alpha-1-antitrypsin deficiency may be responsible for as much as 
one-third of the emphysema in the United States today. Early 
detection and treatment can do much to prevent this tragic waste. 

A screening test for alpha-1-antitrypsin deficiency has been devel- 
oped. This test is now being performed on a number of population 
groups to determine the frequencies of the affected and carrier 
states, and to identify persons who are affected but who have not 
yet developed emphysema, in order to begin preventive treatment 
and possibly genetic counseling. At the same time, investigations 
are underway to define the underlying genetic defect and to find 
possible methods for prevention of the associated emphysema. 

Early detection is an important step toward prevention of COPD. 
A new and promising method has been developed for the early detec- 
tion of changes in lung function and structure which appear to be 
the first sign of chronic obstructive pulmonary disease. This 
method, measurement of closing volume (the amount of air remaining 
in the lungs after smaller airways collapse at the end of expira- 
tion) , detects early changes in the lung which are thought to even- 
tually progress to the clinical signs and symptoms of COPD. It is 
presently believed that in persons with abnormal closing volume 
measurements, but with otherwise normal lung function tests, the 
progression of disease may be reversed and the development of dis- 
abling disease prevented with proper treatment and the cessation 
of smoking. This method is being used on selected populations to 
evaluate its usefulness in mass screening of COPD. A standardized 
protocol for using the method has been prepared to assure compara- 
bility of different studies. 

A workshop on animal models for emphysema was held which identified 
new areas for research into the basic mechanisms of this disease. 
Because cigarette smoking plays a key role in the development of 
COPD, animal models for smoking are being developed to identify the 
agents and mechanisms responsible for lung damage caused by smoking. 
Many investigators are working to define the role of certain enzymes, 
particularly proteolytic enzymes, in the development of emphysema. 
The role of macrophages (a cell found in the lung) in the develop- 
ment of emphysema and chronic bronchitis is also being investigated. 

Advances made in the understanding of the structure and function 
of the lung (described in the preceding section) will also be impor- 
tant to the eventual success in controlling chronic bronchitis and 
emphysema. 



60 



future Recent research progress has been achieved in identifying genetic 
challenges factors associated with COPD. The most immediate challenge for 

the future is how to influence people who are at risk, because of 
genetic factors, to modify their life style in order to avoid 
environmental risks that may lead to COPD. Another challenge is 
to identify the factors in cigarette smoke that produce lung damage. 
Studies to determine the mechanisms by which the lung clears itself 
of particles inhaled in cigarette smoke, the modification of these 
mechanisms by pollutants in the environment, and prospective epi- 
demiologic studies of individual differences in response to the 
harmful effects of tobacco are planned or in progress. Measures 
to modify the smoking habits of the population need to be developed 
in collaboration with behavioral scientists, and especially needed 
are programs to decrease smoking in the young. 

Other host factors, some genetic in origin, may be determinants of 
emphysema and chronic bronchitis. A systematic search for inherited 
enzyme abnormalities that predispose to development of COPD is an 
essential part of the program on host factors. 

We need to develop improved techniques and devices to detect bio- 
chemical, immunologic, or physiologic abnormalities associated 
with emphysema and chronic bronchitis sufficiently early to effect 
reversal of the process, something now believed possible. The 
closing volume test has been shown to be abnormal significantly 
more frequently in smokers than in nonsmokers — in fact, few smokers 
show normal test results. However, the full significance of this 
test is still unclear, and studies are in process to determine the 
relationship of an abnormal closing volume measurement to future 
development of COPD. If, indeed, it can be documented through pre- 
liminary screening studies that this test can identify persons with 
a potentially reversible (and preventable) stage of COPD, then we 
will have a potent new screening test that can be applied to large 
populations in order to detect early disease at a stage when cure 
can be accomplished. 



ACTIONS 



The Institute plans to: 



1. Develop a multidisciplinary program addressed to the problem 
of smoking. This program will include investigation of the 
mechanisms and agents responsible for cigarette smoke injury 

in emphysema and chronic bronchitis, as well as efforts to modify 
smoking habits by means of psychological and pharmacological 
approaches. 

2. Elucidate the role of host factors, including genetic ones, in 
the development of emphysema and chronic bronchitis by conduct- 
ing and extending epidemiological studies. 



61 



3. Enlarge efforts in emphysema and chronic bronchitis prevention 
through the development of improved techniques and devices for 
early detection of reversible diseases and application of new 
knowledge from studies of risk factors and their control. Epi- 
demiological screening studies may be required at a later date 
if this program proves successful. 

4. Initiate controlled clinical trials to evaluate the efficacy 
of current and newly developed approaches to therapy and reha- 
bilitation. 



schedule Present programs relating to pathophysiology and diagnosis of 

advanced disease are being reduced in FY 74 and will be further 
reduced by FY 80. Current and new actions in emphysema and chronic 
bronchitis research are being increased. By early FY 75, a collab- 
orative study on the closing volume test will be extended to popu- 
lation screening for early airways disease, and a joint program will 
be initiated with other Federal and state agencies on the role of 
chronic bronchitis in the development of coal miner's pneumoconiosis. 
New activities in early diagnosis, clinical trials, and multidis- 
ciplinary approaches to smoking reflect increased efforts through 
FY 80. Development of increased interagency contact, begun in 
FY 74 between the NHLI and the National Institute of Mental Health 
to identify studies of mutual interest regarding behavior, smoking, 
and lung disease, will be pursued. Host factor research will 
decrease in FY 76 as ongoing programs on alpha-1-antitrypsin are 
concluded. As new information on other host factors becomes avail- 
able, this program approach will increase in activity again in FY 78. 



4. FIBROTIC AND IMMUNOLOGIC LUNG DISEASES 

program Fibrotic and immunologic lung diseases result from the interaction 
goals f a variety of environmental and host factors. These include viral 
and bacterial infections, diseases of the connective tissue, radia- 
tion damage, exposure to substances such as molds and dust that ini- 
tiate hypersensitivity reactions, and inhalation diseases resulting 
from exposure to substances such as coal dust, silica, asbestos, and 
pollutant gases such as nitrogen dioxide, ozone, and sulfur dioxide. 
Fibrotic and immunologic lung diseases can be prevented or treated 
if the offending substances can be removed or their effects suppressed. 
Therefore, a primary goal of the National Program in this area is 
to disseminate information about the causes of these diseases, as 
these are discovered through research, and how to avoid them. (See 
section on Prevention, Control, and Education). The Institute's 
current research program on fibrotic and immunologic lung diseases 



62 



focuses on asthma, pulmonary fibrosis, hypersensitivity pneumonitis, 
and noninfectious granulomatosis. In cases where exposure cannot 
be avoided or the disease prevented, effective treatment depends 
on understanding the processes leading to disease and minimizing 
their impact on the lungs. 



The research goal is to conduct fundamental investi- 
gations essential to the development of improved 
therapy. 



recent Asthma is an immunologic disease specifically mentioned in the 
PROGRESS National Heart, Blood Vessel, Lung, and Blood Act of 1972. The 
NHLI program focuses primarily on the nature of the pulmonary 
functional impairment. To learn more about the unusually irritable 
airways of asthmatics, the possible interaction between the inhaled 
antigens that stimulate bronchial spasms and nonantigenic inhaled 
pollutants (e.g., sulfur dioxide) are being studied, and the effects 
of pharmacologic mediators (e.g., histamine) are being evaluated. 
Immunologic and allergic bases of asthma are research areas within 
the mandate of other NIH Institutes. 

Early diagnosis of fibrotic and immunologic lung diseases, while 
they are still reversible and curable, is a primary research objec- 
tive. The methacholine challenge test for detecting preclinical 
asthma is currently undergoing evaluation. A multidisciplinary 
group is identifying specific antigens associated with hypersensi- 
tivity pneumonitis and preparing and testing diagnostic skin tests. 
Other investigators are utilizing animal models to investigate the 
role of the immune system in these disorders and to seek ways to 
develop early diagnostic tests. 

Studies in asthmatics following exercise have been performed and 
will now permit attempts at modifying the course of the response. 
Approaches to therapy include: investigations of lung innervation 
to provide an understanding of neural control of bronchoconstriction 
and the basis for developing rational pharmacologic therapy; studies 
of lung mechanics, gas exchange, and blood flow to determine precise 
clinical indications for bronchopulmonary lavage — a therapeutic 
measure used in some resistant asthmatic attacks; and studies of 
behavioral conditioning as a possible way of controlling respiratory 
resistance in asthmatics. 

Pulmonary fibrosis, which may result from chemical, physical 
(radiation) , and microbial injury as well as hypersensitivity 
reactions, includes a group of diseases for which no apparent cause 
has been identified. Studies are underway to elucidate the immuno- 
logic mechanisms that lead to pulmonary injury. Basic information 



63 



is being developed regarding connective tissue protein metabolism 
(collagen and elastin) , and a major effort is being made to stimu- 
late research in this area. Methods for studying cell-mediated 
immunologic responses and circulating antibodies in humans and 
animals have been developed and applied to lung diseases. 

Hypersensitivity pneumonitis, usually a consequence of inhalation 
of allergens, occurs among pigeon breeders, farmers, and workers 
exposed to detergent enzymes. Several multidisciplinary centers 
are conducting research focused on the epidemiology of hypersensi- 
tivity and diffuse interstitial lung diseases. Technology for 
mass screening, both in pulmonary function and immunology, has 
been developed to facilitate epidemiologic studies, and population 
groups have been identified and are being studied. Attempts at 
correlating the levels of exposure with functional and structural 
deterioration of the lung will hopefully result in improved and 
safer environmental and industrial standards. 

Among noninfectious granulomatoses, sarcoidosis is of particular 
epidemiologic interest due to its unusual prevalence among the 
black population in this country (10 to 17 times more common than 
in the white population) and because it is twice as common among 
females as among males. An epidemiologic study of sarcoidosis is 
being developed. 

Animal models of fibrotic and immunologic lung diseases have been 
developed and are valuable for investigating etiologic and patho- 
genetic mechanisms. An animal model of allergic asthma is now 
available and is being used to study the neurologic mechanisms in 
this disorder. Several multidisciplinary projects are utilizing 
animal models of hypersensitivity and diffuse interstitial lung 
disorders, and a program is being initiated to develop animal models 
of sarcoidosis. 



future Where population groups are known to have a high prevalence of 
challenges pulmonary fibrosis or immunologic lung diseases, epidemiological 

studies should be carried out to identify the factors responsible. 
This identification of specific etiological agents is crucial to 
the development of effective control measures aimed at eliminating 
these factors. The Institute will seek to coordinate epidemiologic 
programs through use of standardized methods and protocols and 
increased communication, so that data can be compared. 

Advances in biochemistry, pharmacology, and immunology have not 
yet been brought adequately to bear on problems of lung disease. 
These basic scientific disciplines need to be drawn upon in the 
development of therapy, prevention, and control of immunologic and 
fibrotic lung diseases. Understanding the role of certain endoge- 
nous mediators and their composition and mechanism of action, though 
difficult to achieve, is essential. The specific roles of molec- 
ular mechanisms involved in cell-mediated and antibody-mediated 



64 



immunologic responses in lung disease must be defined. It is anti- 
cipated that the inflammatory and bronchoconstricting responses 
mediated by certain hormonal agents will be better understood in 
the future. The mechanisms of collagen synthesis and degradation 
need to be studied in order to develop therapy directed at specific 
events in the chain of metabolic changes leading to disease. It 
is anticipated that specific components of collagen will be identi- 
fied and that improved methods of assaying elastin will allow 
better understanding of its metabolism in the lung. Techniques for 
diagnosing sarcoid are being developed, and a better understanding 
will be sought of immunologic and neurologic mechanisms of fibrotic 
and environmental lung diseases, asthma, and sarcoid. 

Many animal models of immunologic and fibrotic lung diseases are 
available and represent opportunities for study of the pathogenesis 
of these diseases. 



ACTIONS 



The Institute plans to: 



Seek new information about the synthesis and degradation of 
collagen and the immunologic responses and defense mechanisms 
of the lung through continued and extended multidisciplinary 
programs. These will involve collaboration by immunologists, 
biochemists, physicians, and physiologists. 

Initiate programs to develop pharmacologic agents that will 
modify the alterations in connective tissue metabolism that 
lead to pulmonary fibrosis, and study the use of immunologic 
techniques to stimulate tissue defense mechanisms against 
immunologic lung diseases. 

Initiate epidemiologic studies to investigate etiologic factors 
in population groups characterized by unusual prevalence of 
fibrotic and immunologic lung diseases. 



schedule Attention currently focuses on characterizing the lung structural 

proteins, collagen and elastin, at the biochemical level. Programs 
which are oriented to the synthetic and degradative processes of 
collagen and elastin are being implemented. Programs concerned 
with epidemiology, animal models, and development of a simple 
in vitro test of sarcoidosis will continue through FY 78. Epi- 
demiologic studies of hypersensitivity pneumonitis and fibrotic 
lung disease will begin to produce useful information on the patho- 
genesis and natural history of these disorders by FY 77. By 
redirecting funds from other program areas , both new actions and 
the total program in fibrotic and immunologic lung diseases will 
undergo a substantial increase between FY 76 and FY 80. All of 
the action areas — multidisciplinary approaches, targeted programs, 
etiology and epidemiology — reflect incremental activity between 
FY 76 and FY 80. 



65 



5. RESPIRATORYFAILURE 

program Respiratory failure may occur in many different disorders, both 
GOALS acute and chronic, pulmonary and nonpulmonary . Despite consider- 
able progress in the development of sophisticated therapy, respira- 
tory distress syndromes (acute respiratory insufficiency) of the 
adult remain among the most common causes of postoperative mortal- 
ity and of death related to major trauma. Because acute respira- 
tory insufficiency is potentially reversible if recognized early 
and if treatment is initiated promptly, the major research emphasis 
at present is on identification of factors that predispose to these 
syndromes, studies of the effects of oxygen toxicity, and develop- 
ment of therapeutic devices, especially ventilatory assist devices 
and oxygenators. (See section on Respiratory Assistance.) 



• A program goal is to develop improved techniques for 
detection of potential respiratory failure. 

• Another goal is to develop monitoring devices and 
modes of therapy that are less costly, less compli- 
cated to administer, and more readily available than 
those now in use for respiratory failure. 



recent Various techniques and devices have been developed for detecting 
progress impending respiratory failure. A sensitive spirometer that measures 
the peak acceleration which occurs early in forced expiration is 
currently being evaluated for its ability to detect early airway 
obstruction. Methods have been developed and are being evaluated 
for assessment of the degree of pulmonary edema. Powdered tantalum, 
as a roentgenographic contrast medium, has been clinically used to 
study the structure and function of bronchi, bronchioles, and 
alveoli in diseased lungs. Further developments relative to treat- 
ment of respiratory failure are discussed in the section on Respira- 
tory Assistance. 

future The specific challenges in this area are to improve the devices 
challenges anc j techniques used to detect potential respiratory failure and to 
provide the attending physician with a better description of lung 
function during the period of respiratory failure, thus making it 
possible for the physician to be more responsive to the need for 
improved respiratory care during this critical care period. We 
need to evaluate critically current devices and techniques for 
early detection and subsequent monitoring of respiratory failure. 
New devices that can be easily used by physicians and allied health 
personnel need to be developed to provide more effective management. 
As new devices and techniques are developed, their efficacy must 
be tested in controlled clinical trials. 



66 



Future challenges include the development of a portable, rugged, and 
reliable mass spectrometer for continuous measurements of respira- 
tory gases. Also, microsized, reliable, and stable electrodes need 
to be developed for the continuous in_ vivo gas measurements of p02 
and pC02- In addition to the improved, continuous measurement of 
respiratory and blood gases, a more complete assessment of changes 
in pulmonary function and structure during the period of respira- 
tory failure is a significant challenge. The development and eval- 
uation of new noninvasive devices and techniques are required to 
support the therapeutic measures provided in critical care settings. 
A newly developed technique to continuously measure the ventilation/ 
perfusion ratio may provide an important contribution. In addition, 
new and innovative techniques of lung imagery hold promise for moni- 
toring lung function. 

Despite the fact that respiratory support with positive pressure 
and high oxygen concentrations presently provides the basis for 
therapy during respiratory failure, the long-term effects of high 
oxygen concentrations and continuous mechanical ventilation on the 
lung are still not well understood. Further studies on the effects 
of long-term ventilation, with and without positive pressure, on 
the lung function and structure are needed. In addition, studies 
of the potential dangers to the lung of high oxygen concentrations 
for extended periods must be continued in order to complete our 
understanding of this problem. 



ACTIONS 



The Institute plans to: 



1. Initiate development of devices and techniques for monitoring 
of respiratory function in patients with impaired lungs. 

2. Develop and test improved invasive and noninvasive instruments 
for blood and respiratory gas analysis in patients with lung 
disease. 

3. Develop devices and techniques to detect and monitor resistance 
in small airways and structural and functional abnormalities of 
diseased lung. (See section on Emphysema and Chronic Bronchitis.) 



schedule During the coming year, the initial phase of several programs in 

Respiratory Failure will be completed. The design and development 
of a lightweight, sensitive, and reliable mass spectrometer will 
be completed and ready for clinical test and evaluation. Likewise, 
the design, fabrication, and feasibility test for two new types of 
continuous, in_ vivo blood gas sensors will be completed, and the 
clinical use of the continuous ventilation/perfusion technique will 
be evaluated. Program development will subsequently continue to 
increase gradually through FY 79 with primary emphasis on providing 
improved diagnostic and monitoring capabilities. 



67 



6. PULMONARY VASCULAR DISEASES 



PROGRAM 
GOALS 



Pulmonary vascular diseases, which include cor pulmonale, pulmonary 
hypertension, and pulmonary edema, are serious lung disorders with 
often devastating consequences, and as such are the focus in this 
new program area in lung diseases. Reliable data on incidence and 
prevalence of pulmonary vascular diseases, as well as on the effec- 
tiveness of present modes of therapy, are not available. This is 
largely because present methods for diagnosis and for assessing 
therapeutic progress involve procedures that cannot readily be used 
on very ill or large numbers of patients. If these diseases could 
be reliably identified early in their course they could be effec- 
tively treated. If simple techniques that could be used repeatedly 
without undue discomfort to the patient were available, it would 
be possible to study the course of these disorders and assess the 
long-term benefits of therapy. The causes and development of these 
diseases need to be investigated through the use of animal models 
in an interdisciplinary setting. 



A primary goal of this new program area is to stimu- 
late development of reliable, noninvasive techniques 
for assessing the ventricular hypertrophy associated 
with cor pulmonale, and for diagnosing pulmonary 
hypertension without the need for cardiac catheter- 
ization. 

Another goal is to encourage development of animal 
models of cor pulmonale and pulmonary hypertension 
to be used in the investigation of pathogenetic 
mechanisms of these diseases. 

Multidisciplinary studies must be fostered toward 
understanding the dynamics of fluid, electrolyte, 
and protein exchange in pulmonary edema. 



recent Although it is not accurately known how many patients suffer from 
progress cor pulmonale, this disorder is most often a consequence of emphy- 
sema and chronic bronchitis, themselves chronic respiratory diseases 
of national impact. Autopsy data suggest that pulmonary hyperten- 
sion is also underestimated because at present it can only be diag- 
nosed by catheterization, a procedure not amenable to screening 
large numbers of persons or to use in the very ill. Pulmonary edema 
is more prevalent than generally realized but is usually reported 
only when it is the admitting diagnosis and not when it arises in 
the course of hospitalization or is treated in the outpatient clinic. 
It is a common occurrence in cardiovascular and renal diseases, as 
well as in many pulmonary disorders. With the methods presently 
available, pulmonary edema can only be detected late in its clinical 
course, making prompt therapy of the condition impossible, and thus 
contributing to its morbidity and mortality. 



68 



future Early diagnosis is the first step in treating these pulmonary 
challenges vascular diseases effectively while they are still reversible. To 
evaluate the efficacy of therapy, serial assessments must be made 
of the patient's condition over long periods. Both of these needs 
depend upon development of reliable techniques that are noninvasive, 
safe, and cause minimal discomfort to the patient. Some noninvasive 
techniques have been developed, but none have sufficient promise to 
meet the clinical needs for diagnosing and screening for pulmonary 
hypertension, cor pulmonale, or pulmonary edema. A major challenge 
is to develop promising diagnostic techniques which would make it 
possible to screen large numbers of persons . These techniques 
would be used to identify population groups for the study of eti- 
ologic factors and pathogenetic mechanisms, and for assessing thera- 
peutic regimens. 

New and better animal models need to be developed in the future to 
study the pathogenesis and pathophysiology of cor pulmonale and 
pulmonary hypertension at the molecular and biochemical levels, and 
to further assess diagnostic and therapeutic techniques. Available 
animal models do not adequately represent the disease processes 
known to occur in humans. Fundamental studies are also needed to 
elucidate neural, endocrine, and electrolyte factors in the patho- 
physiology of pulmonary hypertension. Limited work in this area 
shows great promise of yielding information necessary for future 
preventive, therapeutic, and diagnostic efforts. Studies of the 
lung's interaction with vasoactive materials and of the ultrastruc- 
tural and biochemical aspects of vascular smooth muscle need to be 
extended. 

The early diagnosis and prompt therapy of pulmonary edema require 
a thorough understanding of basic pathogenetic mechanisms in terms 
of ultrastructural, metabolic, and molecular changes. Results to 
date suggest that these approaches will pay large dividends, and 
extension of this work with application of new approaches is neces- 
sary. 



ACTIONS 



The Institute plans to: 



1. Extend multidisciplinary efforts to elucidate the dynamics of 
exchange of water, protein, and electrolytes, the biochemistry 
of edema fluid, and metabolic alterations in the edematous 
lung. 

2. Encourage the development of safe, noninvasive methods for 
detecting pulmonary hypertension, cor pulmonale, and pulmonary 
edema. These methods or devices should be sufficiently sensi- 
tive to assess both the presence and progression of the 
disease. 



69 



3. Promote multidisciplinary approaches on the pathogenesis and 
pathophysiology of cor pulmonale and pulmonary hypertension. 
Investigators will be encouraged to develop animal models of 
these diseases , to apply ultrastructural and biochemical tech- 
niques to the study of vascular smooth muscle, and to study the 
metabolism of vasoactive amines by the lung. 

4. Develop epidemiologic programs aimed at determining the true 
impact of cor pulmonale and pulmonary hypertension on the 
population, identifying host factors and other agents respon- 
sible for the etiology and pathogenesis of these diseases, and 
collecting patient populations for evaluating diagnostic and 
therapeutic methods . 



schedule The above actions will be initiated in FY 75, and these efforts will 
be increased gradually through FY 78. 



7. INHALATION DISEASES 

program This new program area is addressed to respiratory diseases that 
goals result from the direct effects of inhaled dusts, vapors, or gases 
and which can be prevented by removal of the offending substances 
or by protecting individuals from them. Therefore, a primary goal 
of the National Program is to disseminate information about the 
causes of these diseases and how to avoid them. (See section on 
Prevention, Control, and Education.) 



• The research goal is to improve detection of the known 
causes of these diseases and thereby prevent their 
development. 



recent A great deal is already known about types of environmental agents 
progress that are associated with industries and occupations. Industrial 
progress often brings related problems; it has brought us many 
benefits, but also pollution. The introduction of the pneumatic 
drill was a tremendous boon to the mining and construction industry, 
but it also greatly increased the incidence of lung disease caused 
by the inhalation of dust particles in the air. Of all occupational 
illnesses, dust inhalation diseases, medically known as pneumoconi- 
oses, are the most serious health problem. The dusts responsible 
for pneumoconioses are not the familiar dusts we wipe off our cars 
and furniture, but the heavy, often harmful dusts that millions of 
American workers (coal miners, insulation workers, foundrymen, 
stone cutters, and other occupational workers) breathe in every 
day on the job. So fine are these dusts that they escape the natural 
cleansing mechanism of the upper respiratory tract and lodge perma- 
nently, inextricably, in the lungs. Some are relatively harmless; 



70 



others can be deadly. Eventually, if exposure is sufficiently high 
and prolonged, the accumulated particles may cause fibrosis, or scar- 
ring of the lung tissue. In many cases, this leads to serious dis- 
ability and even death. 



future Not long ago, the hazard of pneumoconioses was considered confined 
challenges to certain jobs in specific occupations. Today, it is recognized 
that the problem is far more complicated and that sources of these 
diseases have greatly widened. It has been found that not only are 
workers themselves potentially at risk, but also their co-workers 
and, in some cases, the community at large. This last possibility — 
environmental lung disease associated with agents usually encoun- 
tered only by certain workers — has given the problem considerably 
more dimension and importance . 

Authorities who have studied the problem believe that with the 
cooperation of Federal and state agencies, management and labor, 
practically all cases of pneumoconioses can be prevented. Each 
dust-producing job must be studied to decide the best method of 
prevention. Sometimes dust levels can be reduced easily by proper 
ventilation of work areas, removal of dust by suction as it is 
produced, wetting down of materials before they are worked on, or 
by switching from a hazardous material to one that does not cause 
disease. In other cases, the control of dust diseases is an 
extremely complicated matter, involving elaborate and costly 
measures . 

The pulmonary changes resulting from specific inhalation diseases 
are usually fibrotic in nature but may also involve immunologic 
alterations. Consequently, as more is learned about the causes of 
these disorders, it is anticipated that they may be transferred to 
the Fibrotic and Immunologic Lung Diseases program area. 



actions The Institute plans to: 

1. Develop programs to improve the prevention, detection, and 
relief of inhalation diseases. 



schedule The Institute's program on inhalation diseases will emphasize Pre- 
vention, Control, and Education efforts. Research on detection and 
relief of inhalation diseases will be initiated in FY 75 and gradu- 
ally increased through FY 78. 



71 



8. RESPIRATORY ASSISTANCE 

program The development of techniques and devices for providing respiratory 
goals assistance is an important component of the Institute's research 

efforts to combat all diseases of the lung, and especially respira- 
tory failure, and as such is called out as a separate program area 
in this updated plan. Because respiratory failure is a debilitat- 
ing and often fatal disorder that is an eventual complication of 
nearly every respiratory disease, the development of effective 
therapeutic devices is of the greatest importance. 



The major goal of this program area is to apply new 
technology to the treatment of respiratory failure 
and to develop improved rehabilitation devices and 
techniques . 



RECENT 
PROGRESS 



The most significant progress in this program area to date has been 
the development and testing of membrane oxygenators in animals and 
humans. These oxygenators have demonstrated sufficient promise to 
warrant testing in clinical trials under highly controlled condi- 
tions. If such trials demonstrate the efficacy of the devices, 
they could become a valuable mode of therapy to be widely used in 
support of infants with respiratory distress syndrome and adults 
in respiratory intensive care units. 

Research on respirators has led to development of a compact, por- 
table, ventilatory-assist device which can be patient-cycled for 
the changeover from the expiratory to inspiratory phase. This 
device also has automated sigh capability and ability to provide 
a positive end-expiratory pressure. Clinical trials are presently 
underway. 



Despite the therapeutic importance of oxygen inhalation devices 
for patients in respiratory failure, elevated concentrations of 
inspired oxygen may be potentially dangerous . A recent workshop 
provided a forum for review of research progress, exchange of views, 
and assessment of future needs to insure oxygen therapy without con- 
comitant oxygen toxicity. 



future An immediate challenge for providing prompt respiratory assistance 
challenges i s the clinical determination of which patients in respiratory dis- 
tress may benefit from long-term (days) membrane oxygenator support 
and when in the course of their distress such support should be 
administered. Such criteria could provide needed direction to the 
effective clinical use of this new support device and the maximum 
exploitation of its potential. 



72 



Continued development of artificial lung systems is anticipated. 
New approaches and materials could lead to systems with greater 
clinical utility. For example, the search for and testing of new 
oxygenator materials may lead to a device that requires less complex 
blood management during its clinical use. Techniques of blood man- 
agement required by currently available membrane oxygenators pre- 
clude their use in many patients requiring respiratory assistance. 

The search for and testing of various materials for use in oxygen- 
ators will continue. These efforts will lead to improved manage- 
ment of patients with acute and chronic respiratory insufficiency. 
Progress is also anticipated in the development of noninvasive methods 
to assess lung function during respiratory insufficiency and to deter- 
mine the subsequent need for oxygenator support. 



ACTIONS 



The Institute plans to: 



1. Expand programs addressed to ventilatory-assist devices and 
oxygenators to insure improvements in available devices and 
development of new ones. 

2. Test presently available and promising new devices in con- 
trolled clinical studies. 

3. Develop programs to insure the early initiation of treatment. 

4. Continue and extend Specialized Centers of Research where 
sophisticated techniques are available in order to capitalize 
on what is known and to improve present modes of therapy. 



schedule a collaborative program will be initiated soon to establish clin- 
ical criteria for the therapeutic use of membrane oxygenators in 
the management of acute respiratory failure. In addition, the 
design, fabrication, and feasibility studies for several new and 
novel oxygenator designs will be completed. Analysis and moni- 
toring of other forms of respiratory assistance devices will con- 
tinue to be increased in subsequent years, reaching a peak by 
FY 78, in order to provide more effective support to those in 
respiratory distress. 



73 




BLOOD DISEASES AND BLOOD RESOURCES 



The NHLI program in Blood Diseases and Blood Resources is intimately related 
to the Institute's responsibilities in cardiovascular and pulmonary diseases. 
Blood is a vital part of the circulatory system since it is the vehicle in 
which oxygen, nutrients, and other body chemicals are carried through the blood 
vessels to every part of the body, to be exchanged for carbon dioxide, waste 
products, and chemicals which in turn need to be transported away. 

Problems in the blood are often reflected in disorders of the cardiovascular 
and pulmonary systems. Life-threatening situations can arise if the blood clots 
within the heart, blood vessels, and lungs, or if it escapes from the cardiovas- 
cular system, as in hemorrhage, into the tissues (e.g., stroke) or outside of 
the body. Blood that has lost its capacity to clot, such as in the bleeding 
disorders (e.g., hemophilia) can also give rise to life-threatening situations. 



75 



Blood is an organ in its own right, composed of many different elements. In 
addition to the important functions mentioned above, it participates in the 
body economy in a number of ways. It contains important chemicals such as hor- 
mones and enzymes, protective agents (antibodies) against certain diseases, 
factors important in preventing clotting of blood within the cardiovascular 
system, and factors important in promoting clotting of blood when it acciden- 
tally escapes from within the heart and blood vessels. The blood cells defend 
the body against invading organisms and aid in the repair of organs, including 
the vascular system and the lungs. An adequate volume of blood within the cir- 
culatory system is important in maintaining normal blood pressure and perfusion 
of blood to all parts of the body. 

Blood is a very important life-saving therapeutic tool in medicine as well as 
in surgery. Millions of Americans are saved each year by blood or blood com- 
ponent therapy. Many of these individuals would previously have met with cer- 
tain death. Almost 10 million units of blood and 1.7 million liters of plasma 
(the equivalent of an additional 8.5 million units of blood) were collected in 
the United States in 1971 for use in therapy. Studies of blood preservation 
and efforts to reduce immune responses to transfused blood are important in 
the area of organ transplantation as well. 

The plans for developing the Institute's program on blood diseases and blood 
resources as well as the plans for coordination of the National Program were 
outlined in the National Heart and Lung Institute Summary (Volume 1) of the 
National Heart, Blood Vessel, Lung, and Blood Program on May 1, 1973. 

The updated National Program presented here represents an orderly review and 
assessment of NHLI activities in the field of blood diseases and blood resources 
and continues to be responsive to the Legislative Act which specifically requires 
"studies and research into blood diseases and blood, and into the use of blood 
for clinical purposes and all aspects of the management of its resources in this 
country . . . . " 

The program goals, actions, and schedules as set forth in 1973 in the National 
Program, have been reviewed and updated by the Institute and its advisors. 
Recent progress and future challenges for each program area have been identified. 
This updated Program for the next five years, together with the recent progress 
and future challenges identified, are presented here. 

The four areas addressed by the Institute's research programs in blood are: 



1. Bleeding and Clotting Disorders 

2. Sickle Cell Disease and Related Disorders of the Red Blood Cell 

3. Biomaterials 

4. Blood Resources. 



76 



The first, second, and fourth program areas were identified separately in 1973; 
the third, already included in the 1973 Plan, is given separate status in the 
updated research program presented here. In revising its Plan for blood dis- 
eases and blood resources, the Institute has modified some Actions and integrated 
others, resulting in an overall decrease of 15 specific research Actions in the 
updated Plan. These modifications in the program are made in order to take 
advantage of recent progress and future challenges. 



1. BLEEDING AND CLOTTING DISORDERS 

Blood clotting abnormalities are a major cause of death and disability in the 
United States. The National Program addresses two important areas related to 
disordered hemostasis: the hemophilias and the thromboembolic disorders. In 
the case of the hemophilias, life-threatening situations occur as a result of 
excessive uncontrolled bleeding because of failure of the patient's blood to 
clot normally. In the case of thromboembolic disorders, the opposite is true: 
the blood clots too readily, e.g., in the heart, the brain, or the lungs, causing 
life-threatening complications such as heart attacks, strokes, or pulmonary 
embolism. 



The Hemophilias 

program The hemophilias constitute a major national health problem for 
GOALS several reasons. First, treatment must be continued throughout 
the patient's lifetime at enormous costs; the alternative is 
crippling and death. Second, treatment of this single disease 
places one of the largest demands on the nation's blood supply. 
Finally, the impact of this disease on the patient and his immedi- 
ate family is catastrophic in terms of social, psychological, and 
economic costs. The hemophilias are a family of hereditary dis- 
orders in which the patient's blood clots very slowly or not at 
all causing uncontrolled bleeding on injury or during surgery 
unless the appropriate clotting factor is supplied promptly. 



• A major goal of this program is to understand the 
genetic mechanisms which result in the bleeding dis- 
orders known as hemophilias. 

• A second goal is to improve methods of preparing and 
distributing the necessary plasma fractions so that 
they are available to all who need them at reason- 
able cost. 

• A third goal is to allow the hemophiliac and his 
family to improve the quality of their life and to 
make informed decisions about their future, through 
programs of education, screening, and genetic coun- 
seling as described in the section on Prevention, 
Control, and Education. 



77 



RECENT 
PROGRESS 



Research advances in the last two decades have completely changed 
the outlook for hemophilia care. The clotting factors needed by 
the hemophiliac have been identified, partially characterized and 
can now be mass produced from normal donor plasma. Given the 
increasingly more sophisticated management of our national blood 
resource, the hemophiliac can look to better, cheaper, and more 
widely available products for the treatment of his disease. Recent 
experiments in self -administered home care provide the basis for 
the expectation that antihemophilic factor may be used, as is 
insulin in diabetes, to prevent the manifestations of hemophilia — 
the crippling, suffering, expense, and time loss from school or 
work that have been characteristic in the past. Recent experiments 
also indicate that it may be possible to identify the carrier state 
in the prospective mother and through genetic counseling to reduce 
the prevalence of the disease. The NHLI ' s national survey of hemo- 
philia treatment provides an informational basis on which to develop 
effective plans for study and treatment of the disease. 



FUTURE 
CHALLENGES 



Additional progress can be expected in the medical management of 
hemophilia. It is likely that home therapy may become feasible 
and economical in the near future. Self-administration of anti- 
hemophilic factor (AHF) immediately upon the first sign of bleeding 
may help prevent serious side effects such as crippling of joints. 
There is the further possibility that AHF may eventually be used 
prophylactically by the patient in his home to prevent bleeding 
altogether. The concept of comprehensive long-term management of 
hemophilia has not yet achieved wide acceptance and methods of such 
management and counseling need further study and dissemination to 
the public and to the medical profession. (See section on Preven- 
tion, Control, and Education.) In the future it may also become 
possible to transplant normal blood-forming tissue into these 
patients, thereby permanently correcting the disorder. 



Despite the research advances described earlier, basic knowledge 
of hemophilia remains incomplete. A fuller knowledge of the molec- 
ular structure of the clotting factors could lead to even better 
therapeutic approaches through the identification of biologically 
active molecular fragments. Furthermore, the application of newer 
technology can lead to greater production efficiency and reduction 
in cost of antihemophilic factor. Antihemophilic factor derived 
from animal blood should be studied clinically to determine its 
value in treating the occasional patient who develops an antibody 
to the human factor. One common complication of replacement therapy 
is the transmission of the hepatitis virus. Still to be fully 
explored are methods of removal or inactivation of the virus in 
antihemophilic factor preparations. 



78 



actions The Institute plans to: 

1. Support fundamental research on hemophilia, especially on the 
molecular structure of the clotting factors, the chemistry of 
protein fractionation, the physiology of the coagulation sys- 
tem, and molecular genetics; apply these investigations as 
they mature to solve the clinical problems, e.g., greater effi- 
ciency in the production of antihemophilic factor from donor 
blood, the identification of effector sites on the molecule, 
and the isolation of active molecular fragments; extend the 
clinical experiments which indicate that inhibition of the clot- 
dissolving system is useful in the treatment of the bleeding 
crises of hemophilia. 

2. Establish Specialized Centers of Research for the bleeding dis- 
orders. These should cover the full range of disciplines neces- 
sary for a comprehensive approach to hemophilia care. They 
should provide for both basic and clinical research. 

schedule Current targeted research efforts are scheduled for completion by 
FY 75, while grant activities will expand through FY 77. New 
Specialized Centers of Research are planned for FY 75 through FY 77, 
and their support will peak in FY 77. 

Thromboembolic Disorders 

program Thrombosis (clotting of the blood within the blood vessels) and 
goals embolism (clot fragments carried in the blood from their site of 
origin) are often responsible for the crippling or lethal mani- 
festations of heart and blood vessel diseases. They are implicated 
in several of the major causes of death in the United States. Arte- 
rial thrombosis plays a role in heart attacks, stroke, and chronic 
renal disease. Venous thrombosis can result in pulmonary embolism, 
a disorder which hospitalizes some 300,000 persons and contributes 
to the death of more than 50,000 patients annually. Thrombosis and 
hemorrhage in the microcirculation play primary or contributory 
roles in hypertension, stroke, diabetes, cancer, sickle cell anemia, 
and many other disorders affecting virtually every organ in the 
body. The relationship of thrombosis to atherosclerosis is of 
fundamental importance to the nation's health and has far-reaching 
therapeutic implications. 

• The major goal is to increase understanding of the funda- 
mental mechanisms of thrombosis, especially the role played 
by the individual components of clotting and their relation- 
ship to the microcirculation. 

• A second goal is to facilitate detection and treatment of 
thromboembolic disorders. 



79 



The approaches to both venous and arterial thromboembolism share 
two important concepts: (1) their causes involve an interplay of 
the blood coagulation system, the platelets (one of the formed 
elements in the blood) , the vessel lining, and the properties of 
flowing blood, and (2) application of previously accumulated and 
newly generated knowledge in these areas can be expected to pro- 
vide health benefits to a large number of American people. 



RECENT 
PROGRESS 



Risk factors for thrombosis and embolism have been recognized and 
high risk clinical situations have been identified. It is clear 
for instance that patients suffering from hip fracture or under- 
going hip surgery are at very high risk for venous thrombosis and 
subsequent pulmonary embolism. Patients, especially the elderly, 
who are immobilized for any cause are at high risk. Venous throm- 
bosis commonly occurs as a complication of heart failure. Throm- 
bosis is often the first overt manifestation of some forms of 
cancer. Women using oral contraceptives have an increased risk, 
and thrombus formation is the leading complication of prosthetic 
valves and vessels and of the rejection phenomenon in organ trans- 
plantation. 



Recently, advances have been made in the sensitivity of diagnostic 
methods for detecting deep venous thrombosis. Pathologic evidence 
indicates that venous thrombosis is so common that it was found in 
more than 50 percent of autopsied patients who died from any cause. 
The vast majority of these had been unsuspected. There is both a 
pressing need and an opportunity for increasing the acuity of diag- 
nostic methods . 

Work in the last decade on the clot-dissolving agents, urokinase 
and streptokinase, demonstrates that these agents have an important 
potential as treatments for a wide range of thromboembolic disease. 
For example, it has been demonstrated that these agents signifi- 
cantly accelerate the resolution of clots in the lungs (pulmonary 
embolism) . 

Perhaps most exciting is the promise offered by drugs which prevent 
the formation of blood clots by inhibiting the aggregation of blood 
platelets in the blood vessels. Recent laboratory and clinical 
studies indicate that these agents may have an important potential 
in the prevention of a wide range of thrombotic disorders including 
heart attacks. 



FUTURE 
CHALLENGES 



Further efforts are needed to capitalize on past progress in methods 
for detecting venous thrombosis. Hepatitis-free fibrinogen must be 
made available for clinical clot detection studies. Further efforts 
are well justified to identify fibrin and fibrinogen breakdown prod- 
ucts as a key to the diagnosis of thrombosis in the microcirculation. 



80 



In the treatment of thrombotic disease, the greatest opportunity 
exists for full exploration of the potential of the clot-dissolving 
agents, urokinase and streptokinase, for treatment of patients with 
heart attacks, certain types of strokes, and other thromboembolic 
complications of cardiovascular disorders. 

Prevention of thrombotic disease would have by far the greatest pub- 
lic health effect and, fortunately, an opportunity is presented by 
recent studies of blood platelets and the demonstration that the 
platelet aggregation phenomenon is susceptible to drug inhibition. 
Clinical studies are urgently needed to identify the best drugs, 
the most appropriate drug regimens, and the clinical conditions in 
which they should be used. 



ACTIONS 



The Institute plans to: 



1. Encourage fundamental research in thrombosis and in the relation- 
ship between thrombosis and atherosclerosis; support study of 
the function and pathophysiology of the microcirculation; study 
the relation between lipid metabolism and platelet function; 

and encourage study of the role of the coagulation system in 
sickle cell crises. 

2. Support the development of techniques and instrumentation for 
sensitive, reliable, specific detection of thromboembolic dis- 
ease. 

3. Devise and support clinical trials of platelet-inhibiting drugs 
in the prevention of thrombosis in patients at high risk. 

4. Conduct clinical trials of the efficacy of clot-dissolving drugs 
in the treatment of thromboembolic disorders, especially heart 
attacks . 



schedule Present targeted programs will be completed in FY 77. Basic research 
in clotting will receive increased support between FY 76 and FY 79. 
Trials of antithrombotic drugs and studies of methods for early diag- 
nosis of thrombosis will receive additional support, with the former 
peaking in FY 77. 



2. SICKLE CELL DISEASE AND RELATED DISORDERS OF THE RED BLOOD CELL 

The three groups of disorders considered in this section include Sickle Cell 
Anemia and Sickle Cell Trait, conditions closely related to sickle cell disease 
such as Cooley's Anemia, and defects affecting the Red Blood Cell Membrane and 
Enzyme Systems. 



81 



Sickle Cell Anemia and Sickle Cell Trait 



PROGRAM 
GOALS 



Sickle cell trait, the most common inherited disorder in the United 
States, is believed to be present in more than 2 million U.S. citi- 
zens, primarily black. The trait is a relatively benign "carrier" 
form in almost all of these 2 million persons. However, approxi- 
mately 1 in every 500 black babies is born with the life-threatening 
form of the disease called sickle cell anemia. Such individuals 
undergo painful episodes called sickle cell crises. The research 
goals of the sickle cell disease program are to: 



Develop improved therapy for sickle cell disease crisis; 
increase knowledge of the fundamental biology of the 
disease and its complications; and develop effective 
and acceptable methods for education, screening, and 
counseling. 



The goal of educating the public and the medical profession about 
sickle cell disease is discussed in the section on Prevention, Con- 
trol, and Education. 



recent Recent advances have been made in fundamental research on sickle 
progress cell disease. The disease is due to a genetically determined change 
in the chemical substance (hemoglobin) responsible for the oxygen- 
carrying capacity of the blood. The presence of the changed hemo- 
globin (hemoglobin S) is accompanied by distortions in the shape of 
the normally biconcave red blood cells carrying the hemoglobin, 
making these cells less able to survive in the blood circulation and 
less able to move freely through the smaller blood vessels. The 
presence of hemoglobin S in the red blood cells may lead to anemia 
(reduction in the number of red blood cells) and intermittent block- 
age of blood vessels, precipitating occlusive sickle cell crises. 

The NHLI continues to coordinate the HEW Sickle Cell Disease Program 
initiated by the President in 1971. The major objectives of this 
program are: (1) to foster research and development both at the 
fundamental and clinical levels; (2) to initiate and expand commu- 
nity education, screening, and counseling programs; (3) to educate 
medical and allied health professionals about the problems of sickle 
cell disease; and (4) to improve clinical care for victims of sickle 
cell disease. The last three of these objectives are discussed fur- 
ther in the section on Prevention, Control, and Education. 

Studies are currently in progress to develop information about the 
mechamisms involved in precipitating and sustaining the painful 
occlusive crises and to find ways to deal with it effectively. 
Recent results show that the sickling process may possibly be related 
to ATP (an energy-rich substance) depletion and calcium accumulation 



82 



in the cell membrane. The possibility of an associated zinc defi- 
ciency has been observed in some patients. The reasons for the 
increased susceptibility to infection in patients with sickle cell 
disease are being studied. 

Techniques have been developed which improve the ability to detect, 
measure, and study the structure of abnormal hemoglobins, and to 
identify them in the prenatal period, in cord blood and at birth. 
Progress has also been made in screening and diagnostic testing of 
hemoglobin abnormalities. 

It has now been demonstrated that intravenous urea is ineffective 
as an anti-sickling agent in patients in painful crises. However, 
the search for therapeutic approaches continues, and clinical 
studies are planned to test the efficacy of sodium cyanate, a prom- 
ising new agent . 

Collaboration has been developed with other institutions interested 
in sickle cell disease. An agreement has been entered into with 
the Center for Disease Control to continue to conduct workshops in 
hemoglobin detection techniques for the demonstration service proj- 
ects, to set up a hemoglobin proficiency testing program for the 
Federally supported sickle cell projects, and to serve as a refer- 
ence laboratory for abnormal hemoglobins during the coming year . 

future Despite knowledge of the precise defect in the sickle hemoglobin 
challenges molecule, the areas of ignorance about sickle cell disease are 
probably greater than the areas of understanding. Therefore, a 
balanced program must address a variety of problems, from under- 
standing of the red cell to treatment of the patient and education 
of the community. 

The biology of the red cell, the mechanisms of sickling, the effects 
of combinations of sickle hemoglobin and other abnormal hemoglobins, 
the effect on the red cell of agents that may prevent or reverse 
sickling are some of the problems that must be addressed to gain the 
knowledge necessary for rational therapy. 

We must continue to search for therapeutic measures that are effec- 
tive, safe, and simple. As promising therapies are developed, they 
must be tested in clinical trials. Better screening techniques 
need to be developed to detect hemoglobin variants, including sickle 
hemoglobin. We need simple, rapid, accurate, and reliable methods 
suitable for screening. 

Projects in screening and diagnostic testing of hemoglobin abnor- 
malities are presently in an early phase. Future challenges in this 
area include development of accurate prenatal diagnosis of abnormal 
hemoglobins and of innovative methods of education and genetic 



83 



counseling. The greatest immediate need is for dissemination of 
accurate information and for education of the public regarding the 
meaning of sickle cell trait and sickle cell anemia. (See section 
on Prevention, Control, and Education.) 

In developing interfaces with other agencies and organizations, the 
greatest challenge for the future is to develop a well-coordinated 
and uniform approach in all Federal departments and agencies on 
matters pertaining to abnormal hemoglobins . 



ACTIONS 



The Institute plans to: 



Sustain and expand support of studies to understand better the 
molecular structure of sickle hemoglobin, interactions of other 
abnormal hemoglobins with sickle hemoglobin, differences in 
flow patterns between normal and sickle red cells , and the effect 
of various agents on all of these. 

Implement development and testing of improved techniques for 
screening and diagnostic testing of hemoglobin abnormalities in 
patients with sickle cell, Cooley's anemia, and other related 
blood diseases. 

Continue to develop interfaces with other Institutes of the 
National Institutes of Health and other Federal agencies: 
National Institute of Arthritis, Metabolism and Digestive Dis- 
eases; Health Services Administration; Department of Defense; 
Department of Labor; and Veterans Administration. 



schedule in FY 75, more emphasis will be placed on control, including infor- 
mation, education, and demonstration as discussed later in the sec- 
tion on Prevention, Control, and Education. 

Interfaces with other Institutes within the NIH (National Institute 
of Arthritis, Metabolism, and Digestive Diseases; General Medical 
Sciences) and other Federal agencies (Health Services Administration, 
Department of Defense, Department of Labor, Center for Disease Con- 
trol, and Veterans Administration) will continue in the general area 
of hemoglobinopathies with emphasis on sickle cell disease and 
Cooley's anemia. 



Cooley's Anemia and Related Hemoglobin Variants 

program Anemia is a broad term which designates a decrease in the number of 
goals red blood cells. Cooley's anemia (thalassemia) is an inherited dis- 
ease resulting from defective production of the hemoglobin molecule 
which in turn leads to rapid destruction of the patient's red cells. 



84 



On a worldwide basis, thalassemia is the most common inherited 
disease resulting from a single gene mutation. Reliable data on 
its prevalence in the United States are not available. However, 
it is estimated that it occurs in at least 5,000 Americans, largely 
of Mediterranean ancestry. The goals of the research programs in 
Cooley ' s anemia are to : 



Develop a simple screening technique to identify 
carriers; develop better information on the effec- 
tiveness of transfusion programs and means of 
removing excess tissue iron; determine the effec- 
tiveness of splenectomy (removal of the spleen) in 
thalassemia and explore other possible modalities 
of treatment; and increase fundamental knowledge 
regarding control of synthesis of the hemoglobin 
molecule with a view toward achievement of preven- 
tive measures . 



recent Several important advances have been made in this program area. 

progress a method has been developed to synthesize hemoglobin in a cell- 
free system using components isolated from human red blood cells. 
This has subsequently led to the determination that the molecular 
defect in Cooley 's anemia is transmitted by a messenger RNA (a sub- 
stance carrying genetic information) . A biologically active mes- 
senger RNA has been isolated from bone marrow and peripheral cells 
in patients with beta thalassemia. Full understanding and subse- 
quent control of this material may ultimately lead to the capability 
of controlling the error resulting in thalassemia. 

Through a coordinated effort with other institutes and agencies, 
plans are underway to develop an inexpensive, accurate diagnostic 
test and to evaluate treatment of this disorder. Pilot studies 
have been conducted of a simple screening technique for Cooley 's 
trait. 



FUTURE 
CHALLENGES 



We know a considerable amount about the molecular abnormality in 
Cooley 's anemia, but we do not know how to correct it. Present 
treatment is limited to frequent transfusions. While this gives 
temporary relief from the anemia, it burdens the body with excess 
iron that cannot be eliminated. Development of a substance, free 
of serious side effects and effective in reducing the iron over- 
load, would prolong the life of patients with Cooley 's anemia. A 
rational basis for therapy will depend upon further understanding 
of events at the molecular level; therefore, fundamental research 
must be continued. 



85 



We presently have no simple, accurate method for screening for 
Cooley's anemia trait, and therefore, no way of identifying carriers. 
Such a technique needs to be developed. Future challenges include 
the standardization of methods and establishment of a bank of hemo- 
globinopathies which will provide laboratories with standards and 
controls, the development of better modes of diagnosis, better 
chelating agents (for removing excess iron) , other treatment 
approaches and ultimately a method to alter the gene leading to 
the defect. 



ACTIONS 



The Institute plans to: 



1. Continue efforts in Cooley's anemia in coordination with other 
Institutes at the National Institutes of Health and with other 
Federal agencies. These programs will include studies on the 
mechanism of hemoglobin synthesis, clinical research to deter- 
mine the effect of splenectomy and transfusion programs on the 
course of the disease, development of agents for removal of 
excess iron, prenatal diagnostic approaches, and better labora- 
tory methods for detecting the carrier state. 



schedule Most of the Institute's intramural program in blood diseases is 
directly concerned with the acquisition of fundamental knowledge 
in Cooley's anemia and sickle cell anemia. The two diseases are 
inseparably linked at the fundamental level and programs will be 
continued jointly. The programs for research in Cooley's anemia 
and related red blood cell disorders will increase gradually 
through FY 79 and will involve investigator- initiated as well as 
targeted efforts. 



Red Blood Cell Membrane and Enzyme Systems 



PROGRAM 
GOALS 



Disorders of the red cell membrane and enzyme systems are respon- 
sible for a small but significant number of clinically important 
cases of anemia. Perhaps more importantly, the red cell provides 
an easily accessible model for studying physiologic mechanisms 
and metabolic controls common to many cell systems. Red cells 
preserved outside the body (as in blood prepared for transfusion) 
depend on intact metabolism and membrane function for survival 
and function. Therefore, better understanding of these systems 
is applicable not only to blood preservation, but also to the 
preservation of other body cells, tissues, and organs. 



• The major goal of this program is to obtain funda- 
mental answers about membrane structure, function, 
and intracellular metabolic activity and to apply 
this information to clinical medicine. 



86 



recent Progress is being made in a number of areas important to under- 
PROGRESS standing the membrane and enzyme systems of red blood cells. The 
properties of red blood cells which contribute to their viability 
and which support their physiologic function in the circulation 
are being explored, e.g., oxygen transport and regulation of metab- 
olism. Also in progress are studies of physical properties such 
as deformability, adhesiveness, and viscosity; physicochemical 
factors involved in the interaction of blood cells with one another 
and with their suspending medium; and investigation of biochemical, 
clinical, hematological, and genetic factors in diseases in which 
there is an inborn error in the metabolism of the red cells. Other 
studies are concerned with the problems of transport across cell 
membranes, the relationship of chemical properties and functions 
to cell types, transition from fetal to adult characteristics of 
membrane transport, and effects of various agents and conditions 
on permeability. 



FUTURE 
CHALLENGES 



The mechanism of anemia resulting from the interaction of drugs and 
agents with G6PD (an enzyme) deficient red cells requires further 
study. Better understanding of the factors which regulate red cell 
metabolism is necessary in order to extend the preservation of red 
cells beyond a few weeks. Reference laboratories for diagnosing 
and investigating red cell membrane and enzyme disorders must be 
identified and supported. Efforts are being made to encourage those 
institutions that possess the capability of diagnosing rare red 
blood cell deficiencies to submit grant applications for the estab- 
lishment of such facilities. 



The primary challenge for the future is to identify areas that may 
be neglected, to stimulate interest in pursuing these areas, and 
to encourage investigators to collaborate with each other when this 
seems the most advantageous way of meeting national goals. 



ACTIONS 



The Institute plans to: 



1. Continue to support research on normal and abnormal red cell 
enzyme and membrane disorders, and identify reference labora- 
tories for the diagnosis and investigation of these abnormalities. 



SCHEDULE These activities will be expanded gradually in conjunction with 
investigator- initiated work in Cooley's anemia and related hemo- 
globin variants . 



87 



3. BIOMATERIALS 

program An understanding of the basic interactions between blood and the 
goals properties of natural and synthetic materials is essential to the 
development of implantable diagnostic devices, circulatory assist 
devices, oxygenators, and other artificial organs, as well as the 
understanding of the genesis of arteriosclerosis. 



• The goal of the program is to explore the interactions 
between blood and natural and synthetic materials in 
order to develop blood compatible materials for specific 
uses. 



recent Several classes of biomaterials show both promising biocompati- 
progress bility and suitable mechanical properties for use in circulatory 
assist devices and oxygenators as discussed in the sections on 
Circulatory Assistance and Respiratory Assistance. Refined sur- 
face grafting and bonding processes have made possible the develop- 
ment of improved cannulas for a variety of applications. Tissue 
culture research has opened the possibility of lining surfaces with 
living cells and this may represent a promising alternate path to 
the use of synthetic materials in contact with blood. Basic 
research is yielding further information about the changes which 
take place when blood interacts with natural and synthetic surfaces. 

A family of polymers, segmented polyether-urethanes, has been 
developed which combines good mechanical performance with fairly 
good blood compatibility. These materials are currently being 
developed for use in circulatory assist devices. Other polymers, 
sulfonated polystyrenes, also exhibit promising blood compatibility. 
Polyalkylsulfones are other candidate materials which can be modi- 
fied to suit a variety of end uses. Their blood compatibility has 
not been evaluated fully at this time. Other promising artificial 
materials are interpenetrating polymer networks with hydrophilic 
polymers and silicone elastomers which show good blood compatibil- 
ity properties as well as high gas transfer rates for oxygen and 
carbon dioxide. These are being developed for use in artificial 
lungs (oxygenators). 

One current study deals with the physicochemical and mechanical 
evaluation of a new class of so-called "springy" polypropylene 
which has a unique combination of properties for potential pros- 
thetic applications. Preliminary results indicate that the mate- 
rial does not undergo mechanical changes during extended exposure 
to whole blood and is uniquely similar to certain tissues in its 
visco-elastic properties. The required blood compatibility may be 
imparted to this polymer by a variety of surface treatments. 



88 



Significant progress has been made in the development of new 
techniques to impart blood compatibility to otherwise noncompat- 
ible polymers. In particular, certain hydrogel materials have 
been successfully grafted by covalent bonding onto a variety of 
polymeric materials. Further refinement has been achieved in the 
process of ionic bonding of heparin (an anticoagulant) to poly- 
meric substrates. This technique represents a practical tool for 
imparting short-range thromboresistance to some polymers , in par- 
ticular silicone elastomers . 

Improvements have been made in the test systems for assessing the 
blood compatibility of biomaterials . The best synthetic materials 
to date in terms of producing minimal blood changes are hydrogel- 
grafted surfaces and low- temperature isotropic carbons. Good 
results have also been obtained with certain segmented polyether- 
urethanes, mentioned earlier. 

Further progress has been made in evaluating the long-range 
mechanical and physical performance of synthetic polymers in the 
biological environment. The absorption of blood components gives 
rise to highly significant changes which not only affect the 
mechanical performance of the material but also change its surface 
morphology and, hence, biological performance. Studies are in prog- 
ress to establish the long-term bulk and surface characteristics 
of polymeric materials used for cardiac and pulmonary devices. The 
initial work has focused on certain segmented polyether-urethanes. 

future Increased emphasis must be placed on the fundamental aspects of 
challenges the interactions between blood and biomaterials. Improved bio- 
materials suitable for specific physiologic requirements need to 
be developed and improved techniques for modifying and grafting 
surfaces must be explored. 

A better understanding of the mechanical and physicochemical 
properties of natural tissues needs to be developed so that this 
basic information can be used for the synthesis of new materials 
for specific biomedical applications. There is a tremendous 
future challenge in using the natural tissues as models to create 
synthetic systems with properties approximating those of the 
natural tissues. This applies not only to the blood/surface inter- 
actions (blood compatibility) but also to the entire physicochemi- 
cal and mechanical performance of the system. The conformational 
changes which occur during the adsorption of blood proteins on 
biomaterials need further clarification. Better tests for blood 
compatibility are needed since the currently used test systems 
have relatively small surface areas and involve expensive animal 
work. 



89 



actions The Institute plans to: 



Support basic research into interactions of blood components 
with both synthetic materials and natural biopolymers. 

Explore the synthesis and preparation of a variety of bio- 
compatible materials suitable for specific uses in medicine. 

Develop improved methods for the physicochemical and biological 
evaluation and characterization of biomaterials . 



schedule Expansion of the basic science aspects of this program and develop- 
ment of improved testing systems will occur during FY 75 and FY 76. 
The program should reach full strength by FY 78 by which time clin- 
ical trials will be underway. 



4. BLOOD RESOURCES 

The supply of blood and blood components is a critical national problem. Blood 
is a very important therapeutic tool. The demand for blood and blood fractions 
is increasing with no foreseeable limit except that dictated by the practical 
considerations of limited supply. In the face of an increasing demand and a 
limited supply of blood, it is important that economical and efficient use be 
made of the available blood resources. Critical national problems that need to 
be dealt with are: the current wastage of blood, the lack of uniformity of 
blood collected, and the lack of uniform criteria for usage. 

The National Heart, Blood Vessel, Lung, and Blood Act of 1972 significantly 
expands the authority and responsibility of the Federal Government in areas 
which include the use of blood and blood products and the management of blood 
resources. The Act also requires the NHLI to develop a plan for research and 
educational activities related to implementation of a national blood policy. 
Such a plan was presented in the National Heart and Lung Institute Summary 
(Volume I) of the National Heart, Blood Vessel, Lung, and Blood Program on 
May 1, 1973. 

The updated 5-year Plan in Blood Resources is presented here. Four program 
areas are discussed in this section: a Nationwide Blood System, Safety of 
Blood Therapy, Blood Component Therapy, and Transplantation Biology. These 
four areas are discussed in terms of their recent progress, future challenges, 
and actions. One Action, the development of Specialized Centers of Research, 
is applicable to all of the program areas. This Action, together with the 
schedule for the entire blood resources program, is discussed last under Over- 
all Action and Overall Schedule. The program goals are also applicable to all 
program areas and are discussed first as Overall Program Goals. 



90 



Overall 

Program 

Goals 



The present blood resources complex, while providing essential 
services and products, has not consistently maintained an adequate 
supply or achieved the highest attainable quality of blood therapy. 
The goals which the National Program recognizes in the provision 
of blood services to the people of the United States are to promote 
and maintain: 



• Adequate blood supply 

• Highest attainable quality 



Access to the supply for everyone in need 

Efficiency in the collection, processing, storage, 
and utilization of blood. 



Nationwide Blood System 

recent The Institute continues to collaborate with the Office of the 
progress Secretary of the Department of Health, Education, and Welfare, 

the Bureau of Biologies of the Food and Drug Administration, and 
the private sector in order to foster the rapid implementation 
of a truly nationwide blood program. The Institute also continues 
to support research which will assist in the future implementation 
of a Blood Data Collection Center to supply comprehensive and con- 
tinuous information on the supply, size, distribution, and use of 
blood and blood products. Development of a standardized cost- 
finding methodology for blood banks is in progress. Regionaliza- 
tion of blood supply systems is being investigated. Recently, the 
blood banking sector was charged by the Secretary of the Depart- 
ment of Health, Education, and Welfare to submit its plans for 
implementing the National Blood Policy. The Institute will con- 
sider these plans in determining future funding of research pri- 
marily aimed at fostering the implementation of a nationwide blood 
program. 

future The present nationwide blood system is fragmented and poorly 
challenges coordinated at a national level. The result is an inefficient 

use of resources and a compromise in quality. What is known often 
has been applied slowly. Despite these shortcomings, the blood 
service complex has enormous strengths and, in the main, has served 
the American people well. 

The specific future challenge for both the National Heart and 
Lung Institute and other government and private agencies is to 
encourage the development of an appropriate mechanism for imple- 
menting cost-effective systems and regionalization. Other 



91 



important challenges are improved approaches to determine the 
utilization of blood and blood products for specific blood dis- 
eases and other clinical conditions and to assess their immediate 
and future impacts (e.g., projected expansion to supply new needs 
in coronary artery surgery) on the limited national blood resource. 



actions The Institute plans to: 

1. Coordinate its efforts with private and public organizations 
involved in blood banking in the creation of an all-voluntary 
blood donation system and regional integration to increase 
effectiveness . 

2. Assist in the implementation of a Federal Blood Data Collection 
Center, in cooperation with the Bureau of Biologies and the 
Department of Commerce, to provide comprehensive and continuous 
information and evaluation concerning the nation's blood supply, 
its size, distribution, and use. 



SCHEDULE 



See Overall Schedule at the end of this section. 



Safety of Blood Therapy 

recent Three ad hoc committees have been established to coordinate 
progress extramural hepatitis research funded by government agencies or 

institutes. One of the committees supported a workshop on future 
work on hepatitis epidemiology. From this workshop, the National 
Heart and Lung Institute has developed its hepatitis epidemiology 
program. 

A recently completed study indicates that hepatitis B immune 
globulin has no effect in the treatment of acute fulminant hepa- 
titis. Technological improvements in the test for hepatitis 
carriers have made this assay more sensitive and specific. The 
chronic carrier state does not appear to be due to a generalized 
immunodeficiency and no specific deficiency has been found. The 
studies of the efficacy of hepatitis immune globulin in the pre- 
vention of hepatitis in high-risk patients are in progress and 
should yield important answers in this fiscal year. 

Presently available data are inconclusive as to whether cytomegalo- 
virus (CMV) infection results from transmission by transfused 
blood or by activation of latent virus in the recipient. A coop- 
erative trial is presently underway to determine the clinical 
importance of blood transfusion in cytomegalovirus infection. 



92 



Fail-safe systems for donor-recipient identification have been 
developed and tested in limited but successful clinical trials 
at local hospitals. Within the coming year, three devices will 
each undergo extensive trial, and the most effective device will 
be identified. 

The safety of transfused blood is also the underlying concern in 
studies of blood bag materials. Toxicology studies are underway 
on di-2-ethylhexylphthalate (DEHP) , a substance present in blood 
bag materials. Current data show that DEHP is leached from blood 
bags and circulated to the patient's tissues during transfusion. 
The clinical importance of this finding is under investigation. 

future In spite of rapid advances in the understanding of hepatitis, 
challenges primarily serum hepatitis, there is still no way to ensure that 
blood from a given donor will not transmit this disease. Cyto- 
megalovirus disease is also emerging as a common cause of death 
in transfused patients whose immune mechanisms are depressed. 
The role of the blood donor and/or the recipient in the trans- 
mission of cytomegalovirus must be elucidated and means of pre- 
vention developed and implemented. Human error in matching donor 
and recipient remains a major hazard in transfusion therapy and 
fail-safe systems need to be developed and applied. 

Retransf using the patient's own blood constitutes the safest form 
of transfusion therapy. Means must be explored to develop further 
this form of therapy, termed autotransfusion, both by having the 
patient bank his blood prior to need, and by returning to him 
blood lost during surgery. In addition to increasing safety, this 
form of therapy might be expected to reduce significantly the 
demand on the nation's blood resources. 

The final test for hepatitis in blood may have to await the 
identification of new antigens or the development of an entirely 
new approach to testing, perhaps involving a bioassay method. 
Elimination of any chronic virus carrier state by some interven- 
tion technique is not possible at present. We are at present 
only able to define the carrier state without affecting its course. 

The magnitude of the CMV problem remains to be determined. Should 
blood be conclusively proven as the primary mode of CMV transmission, 
a method to detect infectious blood applicable to mass screening 
would be needed to reduce the morbidity and mortality associated 
with CMV. Methods to prevent contamination and to remove the 
contaminating agent would also be explored. 

Future challenges for fail-safe systems of donor-recipient 
identification on the national scale involve the general, large- 
scale acceptability of devices and the high cost of acquiring and 
maintaining them. The potential toxicity of plastics in contact 
with the blood needs further study. 



93 



ACTIONS 



The Institute plans to: 

1. Participate with other agencies in a concerted attack on 
hepatitis which will include development and use of more 
sensitive and practical tests for detecting carriers, studies 
of the carrier state, removal of hepatitis from blood and 
blood products, and development of methods for passive and 
active immunization. 

2. Continue studies in the areas of toxicology of plastic devices 
having contact with blood, the evaluation of fail-safe donor- 
recipient identification systems, and studies which will iden- 
tify the risk of cytomegalovirus infections caused by blood 
donors and/or recipients. 



SCHEDULE 



See Overall Schedule at the end of this section. 



Blood Component Therapy 

recent Research is in progress to explore new methods of plasma frac- 
progress tionation to determine if the components presently being pre- 
pared can be recovered more efficiently and economically. Plans 
have been formulated to develop new fractionation products, and 
these efforts will be implemented shortly. 

future The medical demand for red blood cells, as distinguished from 
challenges other blood components, sets the pace for the collection of whole 
blood. Patients who need red cells often do not need other com- 
ponents. Currently, whole blood is used in more than three- 
fourths of all transfusions, although experts indicate that it 
is necessary in less than one-fourth of the cases. Reducing the 
use of whole blood not only constitutes good medical practice, 
but will increase the availability of components often in short 
supply and needed by other patients. 

Specific research efforts are needed to improve methods for 
storing blood cells, for collecting blood, for maintaining via- 
bility and function of platelets and white blood cells, and for 
improving methods of fractionating blood into its various compo- 
nents. These efforts will require a dynamic cooperative program 
which will involve other government agencies as well as the pri- 
vate sector. 



actions 



The Institute plans to: 

1. Support and participate actively with other interested 

organizations to insure that new fractionation methods are 
devised and/or supported which would cope with the ever 
increasing demands being placed on blood resources, to assure 
adequate amounts of coagulation factors, particularly Factor 
VIII for hemophilia. 

94 



Develop means to enhance and evaluate the appropriateness of 
blood utilization through clearer indications for the use of 
blood components and better methods to assess their effective- 
ness. 

Implement the US-USSR cooperative program on blood transfusion, 
particularly in relation to cardiovascular surgery. 



SCHEDULE 



See Overall Schedule at the end of this section. 



Transplantation Biology 



RECENT 
PROGRESS 



Investigators are actively pursuing means to prevent the sensiti- 
zation of the transplant patient by lowering or eliminating histo- 
compatibility antigens (HL-A) in transfused blood, and studies are 
underway to determine the indications for HL-A typing in platelet 
transfusions. Current studies of in_ vitro methods for removing 
histocompatibility antigens will be followed by clinical trials 
on renal dialysis patients to determine if sensitization to HL-A 
antigens can be reduced or prevented. 

Many methods of removing histocompatibility antigens from blood 
have been studied. Freezing blood appears to destroy histocompat- 
ibility antigens with maximum preservation of red cells, but cost 
factors and the lack of freezing facilities at most institutions 
limit the present utility. Another method of removing histocom- 
patibility antigens by a double centrifugation process is relatively 
simple and appears promising. The clinical studies have demon- 
strated trends which indicate more rapid sensitization in prepara- 
tions with intact leukocytes and platelets but statistically 
significant results have not yet been obtained. 



FUTURE 
CHALLENGES 



In addition to handling blood, a nationwide blood system may also 
be responsible for the preservation, storage, and typing of tissues 
and organs for transplantation. Fundamental knowledge in trans- 
plantation biology will be necessary before transplantation can 
be used more widely and more successfully. Studies of the preven- 
tion of graft-versus-host reactions, the development of better 
immunosuppressive techniques, and the prevention and treatment of 
infection will be undertaken. 



The development of organ preservation devices is required before 
a system of regional or national organ procurement is feasible. 
The design and development of such devices will have to follow 
extensive fundamental research in organ preservation so that the 
factors relevant to successful preservation can be included in the 
design of devices. 



95 



ACTIONS 



The Institute plans to: 

1. Encourage fundamental research (in conjunction with other 
Institutes) in immunology, immunogenetics , and other aspects 
of transplantation biology. 

2. Initiate clinical studies (in conjunction with other Institutes) 
to improve the management of the post- transplant state, such as 
prevention of graft-versus-host reaction, the development of 
better immunosuppressive techniques, and the prevention and 
treatment of infection. 

3. Implement studies to improve organ preservation and procurement. 



SCHEDULE 



See Overall Schedule below. 



Overall 
Action 



Applicable to all of the above blood diseases and blood resource 
problems are Specialized Centers of Research. The Institute plans 
to: 



1. Establish one or two Specialized Centers of Research in Blood 
Diseases and Blood Resources. These Centers could emphasize 
improved blood therapy using cellular components, particularly 
white cells and platelets, and plasma components including 
those used in treatment of hemophilia, and may contain pilot 
plants to test new methods developed for plasma fractionation. 



Overall Increased activities relating to the National Blood Policy are 
Schedule expected in FY 75 and FY 76. The hepatitis program will expand 

through FY 77 at which time peak funding will be reached. Research 
in Transplantation Biology will double by FY 77 and expand gradu- 
ally through FY 79. A Center in Blood Resources will be established 
in FY 75. 



96 



PREVENTION, CONTROL, AND EDUCATION 

Prevention, rather than treatment, of heart, blood vessel, lung, and blood 
diseases offers the greatest promise of reducing death and disability in the 
United States. More effective application of existing knowledge will materi- 
ally reduce disability and death from the complications of these diseases. 
The Institute has provided for expanded future emphasis on bridging the gap 
between research findings and clinical applications by establishing an Office 
of Prevention, Control, and Education. An Assistant Director for Health Infor- 
mation has been recruited from within the Institute. This position is mandated 
by Section 413(d) of Public Law 92-423. The function of this office will be to 
expand and coordinate the various NHLI programs directed toward the goals set 
forth in this section of the Plan. Identification of priority areas is already 
underway. The National High Blood Pressure Education Program (see below) was 
initiated in 1972 and will serve as a model for other education programs iden- 
tified as high priority and launched in the future. Through the study of the 
impact of the various segments of the High Blood Pressure Education Program, 
and consultation with authorities in educational technology and motivational 
analysis, the Institute has begun planning for a more effective national pro- 
gram in public and professional information and education designed to implement 
five overall Actions in the Plan. 



Overall 
Actions 



Develop education programs for each of the categorical program 
areas of the Institute. 



2. Develop better mechanisms, using all media of communication, 
to disseminate knowledge about heart, blood vessel, lung, and 
blood diseases and blood resources. 

3. Establish improved means for direct communication with the 
public. 

4. Expand programs to aid health professionals in improving the 
public's understanding and application of new health knowledge 
and concepts. 

5. Establish improved means for communication with the scientific 
community and the medical profession. 



The overall goal of the Prevention, Control, and Education Programs 
of the Institute is to hasten the control and, in the long run, to 
prevent or lower the prevalence of cardiovascular, pulmonary, and 
blood diseases in the population. The emphasis will be on preven- 
tion of disease, but in order to achieve optimal success, it will 
often be necessary to aid the existing health care delivery system 
in detection of individuals at high risk for a variety of diseases. 
Improved detection will depend in part on increasing the level of 
awareness within the population about risk factors, how to enter 



97 



the health care system, and the importance of patient adherence 
to management regimens once diagnosis has been established. The 
educational components of the Institute's control programs will 
receive the highest priority. 

Professional education and rapid dissemination of research knowl- 
edge from clinical investigation will be stressed to control dis- 
ease. Education and use of paraprofessionals in community efforts 
toward control and prevention of disease will be stimulated. The 
concept of health care delivery team approaches, including team 
members specializing in patient education, is gaining rapid accep- 
tance. Although categorical disease approaches to education, pre- 
vention, and control will be used, the Institute will attempt to 
coordinate and give highest priority to those programs which can 
serve as models for application to other diseases. 

As resources become available, NHLI intends to provide funding for 
local and regional demonstration programs of prevention, control, 
and education which embrace the above principles. These programs 
must involve the several components of the health care system 
within a given geographical area, although they may be primarily 
based in medical schools or major medical centers. In order to be 
maximally effective, funding of these programs will need to insure 
a reasonable degree of long-term, stable support. As stated 
earlier, these programs are not intended to fund health care deliv- 
ery per se , but rather to help effect the transmission of funda- 
mental research advances to the public. The manpower necessary 
for coordination, provision of educational opportunities, and prep- 
aration and dissemination of educational or informational material 
will require support. These programs will be funded on the basis 
of merit as determined by national competition. 

Shorter-term demonstration projects are also envisioned as part of 
the Institute's programs. These demonstration projects will deal 
with specific techniques (e.g., methods of detection) which are 
not currently accepted or commonly in use for disease control. The 
intent of a demonstration project should be to provide clear evi- 
dence that the new technique is applicable to a community situation, 
does not overload the existing health care system, is cost-effective, 
and results in an improved ability of the local health care system 
to respond to the need which the new technique addresses. Once 
the demonstration project has confirmed the feasibility of its 
approach, NHLI funding will be discontinued. Results will be made 
available to the medical community at large by description in 
national publications, through National Research and Demonstration 
Centers, and through voluntary and other health organizations. 
Staff from NHLI and from the demonstration projects themselves will 
be available as consultants to other communities who wish to adopt 
the technique to their own needs. Other examples of demonstration 
projects might be new approaches to continuing education of physi- 
cians in cardiovascular and pulmonary subjects, an improved system 
of assessing patient compliance with antihypertensive regimens, or 
a rapid method for on-site diagnosis and treatment of dangerous 
arrhythmias . 

98 



In order to be maximally responsive to available opportunities, 
both the grant and contract mechanisms should be available for 
funding of the time-limited demonstration projects and the longer- 
term programs for prevention, control, and education. Applicants 
should be able to seek support on a regular basis for ideas in 
these program areas, either by the grant mechanism or by unsolic- 
ited proposals for contract support. In addition to such projects, 
the Institute plans to support demonstrations solicited through pro- 
gram announcements for support of projects or programs of high pri- 
ority under the 5-Year National Plan. 

For FY 75, the highest priority program areas are hypertension, 
arteriosclerosis, inhalation lung diseases, and sickle cell dis- 
ease, in which modest funds are currently available for educational 
programs. In addition, as resources become available, new efforts 
need to be directed to cardiac rehabilitation and emergency cardiac 
medical services, nutrition and coronary artery disease risk fac- 
tors, early diagnosis (including prenatal diagnosis) of respiratory 
distress syndrome in the newborn, emergency treatment of respira- 
tory failure secondary to severe trauma, smoking as a risk factor, 
and improved approaches to blood component therapy. Specific plans 
relating to heart and blood vessel, lung, and blood disease and 
blood resource programs are summarized below. 



HEART AND BLOOD VESSEL DISEASES 



Considerable knowledge is already available on the prevention and control of 
heart and blood vessel diseases. However, achieving the most effective means 
for applying this knowledge to individuals in need requires more specific 
research and evaluation efforts. The prevention and control programs, there- 
fore, seek immediate application of presently available knowledge for prevention 
and control and at the same time strive to make prevention and control measures 
more effective. 

Particular emphasis will be placed on the testing and evaluation of a program 
for the prevention of the two major cardiovascular disorders — hypertension and 
arteriosclerosis. For these two disorders, a sufficient base of knowledge 
exists which could effect substantial reductions in morbidity and mortality if 
the knowledge were implemented through coordinated and comprehensive programs. 
Prevention or amelioration of other cardiovascular disorders requires attention 
in implementing the National Program. Specific programs for hypertension, 
arteriosclerosis, coronary heart disease, and congenital heart disease are dis- 
cussed in this section. The activities described under hypertension and arterio- 
sclerosis are continuations of activities already underway. The activities 
described under coronary heart disease and congenital heart disease are new, 
planned initiatives. 



99 



1. HYPERTENSION 



PROGRAM 
GOALS 



Drug therapy to control blood pressure reduces the incidence of 
strokes and heart failure among persons with moderate and severe 
hypertension. However, only about 12 percent of hypertensives 
are currently receiving adequate treatment. Immediate efforts to 
expand current program initiatives through existing medical net- 
works are urgently needed to bring individuals with moderate and 
severe hypertension under effective treatment. Sustained effec- 
tive blood pressure management in such persons should result in 
a reduction of disability and death by as much as 40 percent when 
compared with expected rates for untreated hypertension. 



• A national goal of the program is to motivate all 
adults to have their blood pressure checked annually 
and for those found to be hypertensive, to urge them 
to obtain proper therapy. 

• Another national goal is to make current knowledge 
of antihypertensive drug management available to and 
effectively practiced by the general practitioners 
as well as the specialists from whom the individuals 
with high blood pressure seek proper therapy. 



RECENT 
PROGRESS 



The National High Blood Pressure Education Program, initiated in 
1972, has completed the preliminary studies of the needs of the 
program, and the Hypertension Information and Education Advisory 
Committee has submitted its recommendations to the Secretary, 
Department of Health, Education, and Welfare. Implementation of 
some recommendations addressed to immediately recognizable needs 
is being planned or has already been initiated. 



In the Hypertension Detection and Follow-up Program, over 10,000 
hypertensive patients from 14 communities of all races and several 
ethnic groups, and both men and women, are being invited to partic- 
ipate in a treatment program. Over one- third of the participants 
will be black and include both rural and inner city residents. 
Special educational efforts are being undertaken to encourage 
patients to attend clinics and to take their medication regularly. 



FUTURE 
CHALLENGES 



Important challenges in prevention and control of high blood 
pressure include the development of simplified medical regimens 
using available antihypertensive drugs and the creation of sys- 
tems which will optimize the utilization of nurses and allied 
health professionals in educational and therapeutic programs under 
physicians' supervision. The problem of motivating patients to 
take and adhere to long-term antihypertensive drug therapy requires 



100 



further research. The use of demonstration programs which seek 
effective implementation of hypertension detection, diagnosis, 
treatment, and follow-up systems in the community in cooperation 
with existing medical and community health resources, needs to 
be explored. 



ACTIONS 



The Institute plans to: 



Continue the Hypertension Information and Education Program 
to expand public and professional knowledge of the dangers of 
high blood pressure and the benefits of effective treatment. 

Establish an education research program aimed at testing 
hypotheses that will lead to new knowledge in methods of edu- 
cation that will (a) increase awareness of the problem; 
(b) define cost-effective methods of delivering patient care 
and patient education, and/or (c) identify methods of increas- 
ing patient compliance. 

Continue a Hypertension Detection and Follow-up Program to 
determine the effectiveness of a systematic approach using 
antihypertensive therapy in reducing mortality among those 
with elevated blood pressure in community-based populations. 



schedule The NHLI ' s current activity in this area will be continued with 
increased emphasis over the next two years and receive sustained 
support thereafter. 



2. ARTERIOSCLEROSIS 

program A number of factors that increase susceptibility to atheroscle- 
GOALS rosis and coronary heart disease have been identified. These 

include elevated blood lipids, high blood pressure, and cigarette 
smoking. These risk factors can be modified and the public needs 
to know how this can be done. 



The program goal is to reduce disability and death 
from arteriosclerotic disease of the blood vessels to 
the heart, brain, and extremities through the preven- 
tion and control of risk factors. 



RECENT 
PROGRESS 



A working group drawn from the National Heart and Lung Institute, 
United States Department of Agriculture (USDA) , and Food and Drug 
Administration (FDA) has been established and has met several 
times. The interests, plans, and priorities of these three agencies 



101 



with regard to prevention and control of hypertension have been 
explored. The FDA's new voluntary food labeling regulations and 
the USDA's planned nutrient data bank (which has been approved 
by the food industry) will eventually make available a wealth of 
nutrition information. 

The National Heart and Lung Institute helps to support certain 
studies by the USDA's Consumer and Food Economic Institute of the 
Agriculture Research Service. These include a literature search 
and documentation and identification of the nutrient composition 
of foods . 

A continuing dialogue between these three government agencies is 
underway. A long-term objective is to evaluate the need for a 
national food analysis laboratory to complement the USDA's planned 
nutrient data bank. 

The nutritional support staffs of both the Multiple Risk Factor 
Intervention Trial (MRFIT) and Lipid Research Clinic (LRC) trials 
(see section on Arteriosclerosis under Research) have been actively 
interacting with university groups and the American Heart Associ- 
ation to explore all available avenues for promoting nutrition 
education. Although the development of education materials and 
techniques appropriate for the MRFIT and LRC trials is the imme- 
diate goal, such material and methods will eventually find more 
general use. General interest in nutrition and heart disease has 
increased throughout the country. The Institute has become increas- 
ingly involved in professional education programs sponsored by 
voluntary and official agencies. The NHLI has also revised its 
informational series on the dietary management of hyperlipoprotein- 
emia. These revised diet manuals are available for physicians and 
nutritionists . 



future It is now possible to identify persons who may be at increased 
challenges risk of developing coronary heart disease, stroke, or peripheral 
vascular disease by measuring their blood lipids, blood glucose, 
blood pressure, and weight, and by obtaining information on ciga- 
rette smoking. An electrocardiogram further improves the predic- 
tion of risk. 

Using these factors as indicators, we can identify the 20 percent 
of the population who are most likely to develop 40 percent of 
the coronary heart attacks, 50 percent of the strokes, and 50 per- 
cent of the clinical peripheral vascular events over a subsequent 
six-year period. This is not an absolute because heart attacks, 
strokes, and peripheral vascular disease also occur in persons 
without such risk factors. However, the highest priority should 
be given to identification of these high-risk susceptible individ- 
uals by relatively simple procedures. 



102 



Once susceptible individuals have been identified, measures can 
be initiated to reduce their risk status through dietary measures, 
drugs for lowering lipids or blood pressure, and modification of 
life styles. This is a difficult task and how to achieve such 
changes in an acceptable manner for large segments of the popula- 
tion remains to be determined. 



ACTIONS 



The Institute plans to: 



1. Cooperate with the Department of Agriculture and other Federal 
agencies having a nutrition-related interest to establish poli- 
cies and education programs on the role of nutrition in heart 
disease; develop, evaluate, and apply dietary survey and coun- 
seling methods in the treatment of hyper lipidemia. 

2. Support, in cooperation with the Department of Agriculture and 
the Food and Drug Administration, a special program to update 
the information on composition of foods in the American market- 
place. 



schedule The Information Program for risk factor detection and prevention 

will be increased in FY 76 and receive sustained support thereafter. 
It is projected that support for nutrition programs will increase 
substantially in FY 75 and increase incrementally thereafter. 



3. CORONARY HEART DISEASE 

program As discussed in the Research section on Coronary Heart Disease, 
GOALS emergency medical care for the person with suspected heart attack 
is a major problem, since there are about 400,000 deaths annually 
from coronary heart disease prior to hospitalization. 



• A goal of this control program is to introduce the 
developments in emergency medical care for the cardiac 
patient into comprehensive emergency care systems. 

• An additional goal is to conduct research on improved 
methods for rehabilitation. 



recent The Institute has been supporting research actions to develop 
progress information for the design and evaluation of emergency care sys- 
tems and is participating with other agencies in an Interdepart- 
mental Committee on Emergency Medical Services. 



103 



The NHLI has convened a task force to study the present state of 
our knowledge as it relates to cardiac rehabilitation. Recommen- 
dations will be developed for clinical implementation of what is 
known and practical, and for initiating effective research where 
necessary. 



future A saving in lives and probably a decrease in disability from heart 
challenges attacks can be achieved by improved emergency medical systems for 
the cardiac patient. In addition, once a heart attack or other 
serious cardiac illness has occurred, the rate and completeness of 
return toward normal functioning in society and enjoyment of life 
remain inadequate. Present studies indicate that disability can 
be minimized and recovery hastened by appropriate attention to the 
medical and psychological factors associated with cardiac rehabil- 
itation. However, the optimal, practical methods for achieving 
such rehabilitation need to be developed, assessed, and demonstrated. 



ACTIONS 



The Institute plans to: 



Contribute, in collaboration with other Federal agencies, to 
the design and analysis of the cardiac elements of emergency 
care systems. Such programs will emphasize the implementation 
of research developments under Actions in the Research section 
on Coronary Heart Disease. 

Explore, in collaboration with the Social and Rehabilitation 
Service, the establishment of demonstration programs for the 
rehabilitation of patients with cardiovascular disease. 



schedule The schedule for the first Action is contingent upon scheduling of 
the comprehensive Emergency Medical System; NHLI components could 
be initiated in FY 75 and continued through FY 78. Collaborative 
efforts on rehabilitation programs were initiated in FY 74 and will 
be continued through FY 80 . 



4. CONGENITAL HEART DISEASE 

program Recognition of congenital heart disease is particularly difficult 
GOALS during the newborn period. Yet this is the period during which a 

substantial fraction of deaths from congenital heart disease occurs. 



• The goal of this control program is to recognize and 
manage congenital heart disease in the newborn. 



104 



RECENT 
PROGRESS 



New investigations and the development of a variety of diagnostic 
techniques are providing capabilities for more ready and accurate 
assessment of congenital heart disease. Also, there has been an 
increased understanding of the pathophysiology of the disease pro- 
cesses and their symptoms. These new developments are being com- 
bined to allow for better and earlier recognition of congenital 
heart disease in the neonate by nursery staff and physicians. For 
example, new investigations recently begun in the field of ultra- 
sonic imaging by acoustical holography provide a new capability 
for examining the anatomy of a newborn child in the manner of low 
resolution X-ray fluoroscopy, but without the use of X-rays. Thus, 
normal and abnormal anatomical structures and physiologic functions 
(e.g., movement of joints, flow of blood in specific vessels, opera- 
tion of heart valves) can be visualized directly in a way believed 
to be nonhazardous to the infant. The nontraumatic nature of the 
method has resulted in rapidly increasing application of ultra- 
sonic imaging examinations to large numbers of pregnant women in 
the United States and abroad. 



future A substantial saving in lives can probably be achieved by early 
challenges recognition of cardiac problems in the newborn and the establish- 
ment of specialized groups to deal with these problems. 



ACTIONS 



The Institute plans to: 



Explore the feasibility of demonstration programs for the early 
recognition of cardiac (and respiratory) problems in the new- 
born. Such programs will emphasize intensive professional edu- 
cation, development of instrumentation for improved detection, 
better interhospital communication and transport, and the avail- 
ability of diagnostic and surgical facilities for treating crit- 
ically ill infants. 



SCHEDULE 



The program will be initiated in FY 76 and continue through FY 80. 



LUNG DISEASES 



The major emphasis in prevention, control, and education in the lung diseases 
area will focus on control programs in inhalation diseases . Other efforts 
include programs in fibrotic and immunologic lung diseases, pediatric pulmonary 
diseases, respiratory failure, and smoking in emphysema and chronic bronchitis. 

1. INHALATION DISEASES 

program This new program area is directed toward preventing or treating 
goals inhalation diseases by removal of the offending substance or by 
protecting individuals against exposure to them. 



105 



A primary goal is to disseminate information about 
the types of dusts, vapors, and gases that can cause 
inhalation diseases and how to avoid them. 



recent Improved standards in terms of exposure levels have been developed 
progress f or asbestos-related industries. Anticipated in the future are 
improved and safer standards for silica as well. 



FUTURE 
CHALLENGES 



A great deal is already known to the scientific community about the 
types of environmental agents associated with industries and occu- 
pations. It is essential that this information be widely dissemi- 
nated to community physicians and the lay public. 



actions The Institute plans to: 

1. Develop a program of education for physicians and the lay pub- 
lic with regard to inhalation diseases. This will be accom- 
plished through workshops for physicians, literature for the 
public, and control programs addressed to avoidance of noxious 
dust, vapors, or gases. 

schedule This new activity was initiated in FY 74 and will undergo incre- 
mental increases through FY 80. 



2. FIBROTIC AND IMMUNOLOGIC LUNG DISEASES 



PROGRAM 
GOALS 



Fibrotic and immunologic lung diseases are induced by external 
agents and can be prevented or treated by removal of these agents 
or suppression of their effects. 



• A primary program goal is to disseminate information 
about the causes of fibrotic and immunologic lung 
diseases and how to avoid them. 



RECENT 
PROGRESS 



FUTURE 
CHALLENGES 



A symposium, oriented toward fibrotic and inflammatory lung dis- 
eases, was held during a recent New York Academy of Science meet- 
ing. This symposium, attended by general physicians as well as 
researchers in the field, was important in encouraging the exchange 
of information necessary for preventing these diseases. 

Available knowledge about external agents implicated in the devel- 
opment of immunologic and fibrotic lung diseases needs to be widely 
disseminated to the lay public as well as to physicians. This is 



106 



essential to prevention of these diseases. Specific future 
challenges for the Institute include the organization of meetings 
and workshops for the public and general practitioners, and the 
preparation of literature for dissemination. 



actions The Institute plans to: 

1. Develop a program of education of physicians and the lay pub- 
lic with regard to environmental agents implicated in pulmonary 
fibrosis and immunologic lung diseases. This will be accom- 
plished through workshops for physicians, literature for the 
public, and control programs addressed to avoidance of etio- 
logic agents in the community. 



SCHEDULE 



The program in education regarding fibrotic and immunologic lung 
diseases will increase incrementally from FY 76 to FY 80. 



3. PEDIATRIC PULMONARY DISEASES 

program About 50,000 babies are born each year with hyaline membrane 
goals disease. More than half of these will die unless given prompt 

treatment. Research programs in pediatric pulmonary diseases are 
focused upon the development of more effective diagnostic and 
therapeutic methods. Until sufficient knowledge is gained about 
prevention of hyaline membrane disease, the only hope for these 
patients lies in prompt diagnosis and treatment. 



The primary goal will be to initiate prompt diagnosis 
and therapy of hyaline membrane disease. 



RECENT 
PROGRESS 



While specific demonstrations have not been initiated, research 
results with respect to continuous positive pressure ventilation 
and early diagnosis have been disseminated through journals and 
at meetings. In addition, a workshop on pediatric pulmonary dis- 
ease has been held and a report disseminated to the pulmonary 
community. 



future In order to initiate prompt diagnosis and therapy, available 
challenges information about pediatric pulmonary disease needs to be dissem- 
inated to appropriate forums in a meaningful way. The major chal- 
lenge in this area is to improve communication between the Institute 
and the pulmonary biomedical community. 



107 



ACTIONS 



The Institute plans to: 



Develop education programs, addressed to pulmonary and commu- 
nity physicians, to provide presently available information 
about treatment of hyaline membrane disease. This will be 
done through demonstration projects and workshops. 



schedule These education programs will be phased-in subsequent to the 
steadily increasing activities in therapy described under the 
Research sections on Pediatric Pulmonary Diseases and Structure 
and Function of the Lung. They will thus be able to capitalize 
on information accruing from other new actions . 



4. RESPIRATORYFAILURE 

program Considerable progress has been made in the development of therapy, 
goals but unless treatment is initiated promptly by experienced person- 
nel, respiratory failure will lead to death in more than half of 
those affected. 



The first goal of the program in this area is to 
disseminate the knowledge needed to save lives through 
early recognition and treatment of respiratory failure. 



RECENT 
PROGRESS 



The information available on hyaline membrane disease is being 
applied in several medical centers, resulting in significant 
decreases in infant mortality rates. To improve and evaluate the 
effectiveness of continuous positive airway pressure as primary 
treatment in many cases of severe respiratory distress syndrome, 
several groups of investigators are using common criteria for 
diagnosis of the syndrome and for initiation and termination of 
the treatment. 



Two groups are now working on adult positive ventilation tech- 
niques in intensive care units, and further improvement and dis- 
semination of this and other recently developed procedures are 
anticipated. 



future Available knowledge about detection and treatment of respiratory 
challenges failure needs to be widely disseminated to community physicians 
and allied health personnel, as well as to pulmonary physicians. 
Specific future challenges are to increase the number of centers 
participating in the treatment of infant and adult respiratory 
distress and to simplify the procedures and equipment so that 
smaller hospital units, as well as the larger centers, may apply 
this knowledge. 



108 



actions The Institute plans to: 

1. Initiate demonstration projects in which available information 
will be widely disseminated to educate pulmonary and community 
physicians and allied health personnel in what is known about 
respiratory failure. 

schedule The major new activity will be demonstration programs. Educational 
activity will undergo a delayed increase, capitalizing on new infor- 
mation accruing from treatment studies . 



5. EMPHYSEMA AND CHRONIC BRONCHITIS 

program Cigarette smoking is believed to be a prime factor in the etiology 
goals or exacerbation of chronic bronchitis and emphysema, and a contrib- 
uting factor to environmental lung diseases, including the pneu- 
moconioses and hypersensitivity lung diseases. Up to 20 percent 
of smokers have chronic obstructive lung disease and almost all 
patients with this disease are smokers. Extensive studies document 
conclusively that cigarette smokers are far more likely to develop 
emphysema than nonsmokers. Also, once developed, emphysema pro- 
gresses much more swiftly in those who smoke. Repeated exposure to 
pollutants in the air also contributes to the development and pro- 
gression of the disease. 

The principal cause of chronic bronchitis is prolonged irritation 
of the bronchial tube linings. Smoking, air pollution, and recur- 
rent infections are the main irritants for chronic bronchitis, as 
well as for emphysema. The public needs to be informed about the 
potential seriousness of persistent or recurrent coughs and short- 
ness of breath and about ways to protect against progression of 
these diseases. 



The program goal is to modify the smoking habits of 
persons at risk of developing lung diseases, and to 
extend successful anti-smoking programs to the general 
population. 



recent The difficulties in modifying human behavior are well-recognized. 

progress to achieve the stated program goal, research is urgently needed on 
the behavioral aspects of smoking. Institute Actions in support 
of such research are discussed in the section on Research programs. 

In instituting an educational program on emphysema and chronic bron- 
chitis for the lay public, NHLI has issued information pamphlets for 
the public and has informed community physicians of its programs at 
a recent meeting of the American Lung Association. 



109 



Research programs designed to promote early detection of emphysema 
and chronic bronchitis should ultimately provide a basis for inter- 
vention and/or prevention. In addition, environmental risk factors 
are being identified, which will provide a necessary first step 
toward prevention. 



future A first step is the identification of persons at risk of develop- 
challenges i n g chronic obstructive pulmonary disease, especially those indi- 
viduals who are predisposed because of genetic characteristics. 
When populations have been identified, education programs effec- 
tive in preventing smoking will need to be devised. The difficulty 
of motivating people not to smoke is well-known and presents a 
major challenge for the future. Sophisticated motivation approaches 
must be developed in cooperation with behavioral scientists to 
modify the smoking habits of persons at risk and, in general, large 
population groups. Those who have not yet acquired the habit should 
be discouraged from doing so through effective educational programs. 

We also need to prevent or modify smoking in persons who live or 
work in environments with unusually high concentrations of air 
pollutants, dusts, or other environmental agents implicated in the 
development of lung diseases. 



ACTIONS 



The Institute plans to: 



1. Develop a program, in collaboration with experts from other 
Federal agencies, to modify effectively the habits of smokers. 

2. Develop an education program to alert the lay public to the 
dangers of smoking in relation to chronic obstructive pulmonary 
diseases and environmental lung diseases, and urge smokers in 
populations at special risk to participate in programs to modify 
their smoking habits . 

These programs on smoking will be developed in collaboration with 
scientists concerned with the harmful effects of smoking on the 
cardiovascular system as well. 



schedule Behavioral and educational programs will be initiated in FY 75 to 
continue for five years . 



BLOOD DISEASES AND BLOOD RESOURCES 



Blood diseases and blood resources, as discussed in the Research section, are 
closely interrelated with heart, blood vessel, and lung diseases, and are impor- 
tant and integral parts of the National Program. Major prevention, control, and 
education programs in these areas are addressed to Sickle Cell Anemia and Cooley's 



110 



Anemia. These programs will emphasize education of the public, screening, and 
counseling. The NHLI is also supporting other programs in blood diseases and 
blood resources which focus on hemophilia, thromboembolic disease, and educa- 
tion about the nation's blood resources, control of hepatitis, and various 
aspects of organ transplantation. All of these programs are discussed below. 



1. SICKLE CELL ANEMIA AND COOLEY'S ANEMIA 



PROGRAM 
GOALS 



Despite the fact that much is known about sickle cell disease and 
Cooley's anemia, the general public, including actual and potential 
victims, have a poor understanding of these disorders and their 
significance. Both diseases can cause great suffering. It is 
estimated that somewhat less than 50,000 Americans suffer painful 
episodes, or "crises," due to sickle cell disease, and at least 
5,000 Americans suffer the effects of Cooley's anemia and require 
repeated blood transfusions in order to survive. In both cases, 
the diseases are transmitted by carriers to their offspring, if 
both parents carry the trait. Thus, education and control programs 
are important to the prevention of these diseases. The Institute 
is developing a program to expand community education to increase 
public awareness of these diseases and to educate these individuals. 



The goals of the control program are to inform the 
public about sickle cell disease and Cooley's anemia 
and to demonstrate techniques for appropriate screen- 
ing and counseling. 



recent Programs are being developed to further expand the dissemination 
progress f information on sickle cell disease, utilizing nongovernment 

participation. Continuing education programs are being provided 
for physicians and paramedical personnel to emphasize established 
approaches as well as new developments in sickle cell disease 
through the programs in the Comprehensive Sickle Cell Disease Cen- 
ters. Standardized techniques of screening (electrophoresis fol- 
lowed by confirmatory solubility) are being incorporated into 
comprehensive screening programs. 



FUTURE 
CHALLENGES 



We need to determine the prevalence and distribution of sickle cell 
disease and Cooley's anemia in this country, particularly the prev- 
alence of carriers of the trait; provide accurate and up-to-date 
information on these diseases; initiate and expand appropriate 
community education, screening, and counseling programs; educate 
the medical and allied health professions about the problems of 
these diseases; identify and provide guidance for the management 
of the resulting psychological, sociological, and economic problems; 
and assist individuals with these disorders to attain their maximum 
potential in life. 



Ill 



actions The Institute plans to: 

1. Develop, in collaboration with other Federal agencies, programs 
to provide accurate information on sickle cell disease and 
Cooley's anemia; education for the general public, population 
groups at risk, health professionals, allied health profes- 
sionals, educators, employers, and insurers of individuals who 
have these disorders; methods to best counsel affected individ- 
uals; and proper rehabilitation approaches when applicable. 

2. Evaluate clinical approaches for the treatment of these dis- 
orders and other developments in the field and insure that the 
ones that are effective are incorporated into the health deliv- 
ery system. 

schedule Screening and Education Clinics for sickle cell disease will con- 
tinue to be heavily supported in FY 75. Information and education 
programs on both sickle cell disease and Cooley's anemia will be 
supported in FY 75 with a gradual reduction of activity from FY 76 
to FY 80. 



2. HEMOPHILIA 

PROGRAM Public awareness is fundamental to management and prevention of 
goals hemophilia. Although severe hemophilia affects only a known popu- 
lation of 25,000 in this country, it is a major national health 
problem. Treatment is very costly and must be continued throughout 
the patient's lifetime, thus demanding a large fraction of the 
nation's blood resources. Since the disease is hereditary, edu- 
cation of the public can be instrumental in its prevention. 



The goal of this prevention program is to educate 
the patient, the physician, and the general public so 
that patients with hemophilia and their families may 
make informed decisions regarding their own lives. 



RECENT 
PROGRESS 



There are no current education efforts in this area. The Institute 
is cooperating with the National Hemophilia Foundation and other 
national organizations to develop programs for the future. A Center 
for Blood Disease is in the planning stages and methods of education 
and counseling for hemophilia may be studied through this mechanism. 



FUTURE 
CHALLENGES 



The NHLI plans to study methods of genetic counseling and its impact 
on the hemophilia community, techniques of "total care" for hemo- 
philiacs, and methods of minimizing the cost of hemophilia care for 



112 



the patient. Plans will also be developed for education programs 
directed toward the affected individual, the individual's family, 
the medical profession, and the general public. These efforts 
will be coordinated with those of the National Hemophilia Founda- 
tion. 



ACTIONS The Institute plans to: 

1. Explore, in cooperation with other agencies, information, edu- 
cation, and genetic counseling techniques aimed at improving 
hemophilia therapy and preventing hemophilia. 



schedule Information, education, and approaches to genetic counseling in 
hemophilia will receive increased support in FY 76 and FY 77. 



3. THROMBOEMBOLIC DISEASE 

program Thromboembolic disease causes or contributes to a great variety 
GOALS f diseases in all parts of the body, including heart attacks, 

kidney failure, stroke, pulmonary embolism, and disorders of the 
microcirculation. Key to the prevention and control of thrombo- 
embolic disease is the identification of persons who may be at 
risk. Several risk factors associated with high risk for thrombo- 
embolic disease are known and it is now possible to identify those 
persons who may be at increased risk of stroke, pulmonary embolism, 
and thrombophlebitis and to take steps to prevent these disorders. 



• The major program goal is to reduce disability and 

death from thromboembolic disorders by prevention and 
control of risk factors. 



recent Added emphasis is currently being placed on this program. Inter- 
progress national congresses on thrombosis and hemostasis were held in 

1972 and 1973 and have provided a forum for discussion of throm- 
bosis as a major world health problem and as part of a planned 
attack on this problem. Another more modest conference focused 
on clot-stabilizing enzymes and a workshop was conducted to review 
existing knowledge about the relationship of thrombosis to the 
development of myocardial infarction. 



future Because rapid communication is important for advance in thrombosis 
challenges an( j related fields, conferences on timely topics are planned to 
disseminate information as it is developed through research. 



113 



ACTIONS 



The Institute plans to: 



Explore, in coordination with other agencies, techniques for 
educating the medical community and the general public about 
risk factors and preventive measures in thromboembolic disease. 



schedule This program was initiated at a modest level in FY 74 and will be 
receiving gradually increased emphasis through FY 80. 



4. BLOOD RESOURCES 

program An adequate supply of blood resources is vital to the treatment, 
goals prevention, and control of many major diseases, including the ones 
addressed by the National Program. Not only must there be adequate 
supply of these resources, but they must also be of high quality 
in order to provide effective treatment and to avoid transmission 
of disease, such as hepatitis. Currently, neither adequate supply 
nor high quality blood is fully assured by the nation's operating 
blood service complex. Whole blood and blood components are col- 
lected by this complex and distributed throughout the nation. 
Special efforts are needed to assess the problems involved and to 
encourage more effective and economic utilization of these resources. 
A continuing program must be carried out for professional and public 
information and education about blood resources and the use of 
effective blood management systems. This is especially true of 
blood component therapy. 



• The goal of this program is to achieve better manage- 
ment of the nation's blood resources. 



RECENT 
PROGRESS 



Two types of education efforts are being developed: (1) Education 
of technical/medical professionals to assure that whole blood is 
separated into its component parts and that the components are 
appropriately stored and made available to users; and (2) Efforts 
to influence the demand sector of the blood banking complex 
regarding optimal use of blood components in order to moderate 
the demand on the nation's blood resources. 



future We need to develop ways to educate physicians regarding optimal 
challenges use f blood components in order to moderate their demands on the 
nation's blood resources. The target population for the technical 
education efforts is the regional component of the coordinated 
nationwide blood system which is currently evolving in the United 
States. To stimulate optimal use of blood, attention will be 
directed at hospital blood banks and, at least initially, selected 



114 



populations of physicians, in particular, surgeons and anesthesi- 
ologists. Efforts also need to be made to evaluate the impact of 
the hepatitis program on the nation's health and to bring the 
results to the practicing physician, blood banker, high risk indi- 
vidual, and the general public. 

The NHLI also plans to assess the psychologic, sociologic, and 
economic aspects of organ donation and transplantation. Motivation 
for organ donation and regionalization of "organ banks" will be 
investigated and evaluated in concert with the National Blood 
Program. 



ACTIONS 



The Institute plans to: 



1. Support efforts to educate and influence physicians regarding 
optimal use of blood components and autotransfusion in order 
to moderate demands on the nation's blood resources. 

2. Develop a coordinated program for hepatitis epidemiology and 
control. 

3. Encourage efforts to develop a system of organ procurement on 
a regional and national basis. 

4. Promote public dialogue on the ethical and legal problems 
associated with organ transplantation. 



schedule The Institute's efforts in education programs in blood therapy will 
be increased gradually over the next five years. 



115 



IV. PROGRAM COORDINATION 



IV. PROGRAM COORDINATION 



The National Heart, Blood Vessel, Lung, and Blood Program is designed to use 
national resources to attain the national long-term goal of improving the health 
of the American people. The achievement of a truly National Program remains a 
major challenge to the Institute. While we must not belittle the many real 
problems that remain in terms of National Program coordination, the Institute 
has made considerable progress in mobilizing interest in the Program. Through 
the National Program, the NHLI has a great opportunity to stimulate collabora- 
tive efforts at all levels and with all sectors of our society. In this manner 
the resources and direct efforts of the Institute have a multiplier effect far 
beyond what has been previously possible. 

The Institute has, in the past, participated in many key collaborative efforts 
with other organizations throughout the nation. Such collaboration will con- 
tinue to be expanded. During the planning stages of the National Program, both 
public and private sectors were called upon for inputs. These inputs to the 
Program, as detailed in the National Heart and Lung Institute Summary (Volume I, 
dated May 1, 1973), include other Bureaus, Divisions, and Institutes of the 
National Institutes of Health, other Federal agencies, and private, non-Federal 
and voluntary organizations. 

In implementing the Program, this Institute continues to serve as the principal 
coordinator of a management system depicted in Volume I and reprinted here 
(Figure 1). As the focal point, the Institute can: 



Promote coordination of research and prevention, control, and 
education activities with many other organizations 

Assess the ordered sequence of program activities from basic 
research to demonstration in the community 

Evaluate the overall National Program in terms of ongoing and 
projected activities 

Gauge the impact of the Program on the health of the American 
people. 



117 



















































♦ 










New Program 
Concepts 




Agency 
Resource 
Allocation 




Health 
Impact 








I 












i 








Interagency 
Coordination 
• Program Scope 
► Priorities 






























PROGRAM EMPHASIS AS DERIVED 
FROM AGENCY MISSION 










♦ 




* 




* 










Acquisition 

of New 
Knowledge 




Development 
of Existing 
Knowledge 




Application 
of Existing 
Knowledge 










* * 




« ♦ 




* » 












PROGRAM EVALUATION 




Health 

Care 

Delivery 














♦ 






1 






Public and Professional 
















In 


formation and Educat 


on 















Figure 1. Coordination and Implementation of the National Program 



From a central position, the Institute can review current knowledge and activi- 
ties in each program area addressed by the National Program and thereby assure 
balance among the program areas. Most importantly, the Institute as coordina- 
tor of the National Program will be able to stimulate the development and dis- 
semination of information to the public and the medical professions in a respon- 
sible and timely manner. 

Key collaborative efforts in areas related to the problems addressed in the 
National Program are conducted through a variety of mechanisms. Some of these 
national efforts are summarized below. Highlights of relevant cooperative agree- 
ments between the NHLI and other countries are also presented, insofar as these 
represent extensions of a National Program which addresses transnational disease 
problems. 



118 



NATIONAL COLLABORATION 

A key formal mechanism for coordinating national efforts related to the National 
Program is the Interagency Technical Committee on Heart, Blood Vessel, Lung, and 
Blood Diseases and Blood Resources (IATC) . The IATC was established by the Sec- 
retary of the Department of Health, Education, and Welfare in November 1972, in 
accordance with the National Heart, Blood Vessel, Lung, and Blood Act of 1972. 
This Committee, chaired by the Director of the National Heart and Lung Institute, 
is responsible for coordinating Federal agency activities related to heart, blood 
vessel, lung, and blood diseases and blood resources to assure their adequacy and 
technical soundness. The Committee provides a forum for communication and exchange 
of necessary information. 

The Committee is comprised of representatives from the following components of the 
Department of Health, Education, and Welfare: 

Alcohol, Drug Abuse, and Mental Health Administration 

Center for Disease Control 

Food and Drug Administration 

Health Resources Administration 

Health Services Administration 

National Institutes of Health 

Social and Rehabilitation Service 

Social Security Administration. 

Also on the Committee are representatives from other Federal departments and 
agencies as follows: 

Department of Agriculture 

Department of Defense 

Department of Transportation 

Atomic Energy Commission 

Environmental Protection Agency 

National Aeronautics and Space Administration 

National Science Foundation 

Veterans Administration. 

119 



During the initial planning effort, the Committee provided input to the National 
Program by advising on goals, opportunities, and needs. It also assisted the 
Institute in compiling an inventory of ongoing programs related to the National 
Program. This inventory, published as Volume V of the National Heart, Blood 
Vessel, Lung, and B.'.oorl Program, identified, within only the agencies represented 
on the Committee, £.;?prc ximately 3,500 research areas related to the National Pro- 
gram. These programs •represented more than $130 million in Federal outlays above 
the NHLI ' s budget for these related programs . 

Presently, the Committee is updating the information contained in Volume V (by 
provision of FY 73 data) and reviewing the status of past and present interagency 
coordination and the prospects for broadened agency participation in the National 
Program. 

In addition to the information displayed in Volume V last year, there are other 
Federal organizations which are not represented on the IATC, but which conduct 
or sponsor related research and/or prevention, control, and education activities 
in heart, blood vessel, lung, and blood diseases and resources. Furthermore, 
24 non-Federal voluntary organizations with related programs were identified in 
Volume I last year. The NHLI already collaborates with many of the Federal and 
non-Federal organizations and plans even greater collaboration in the future 
among all the sectors of our society concerned with these disease problems. Dis- 
cussed below, for each major disease category, are some key ongoing collaborative 
efforts in which the NHLI participates. 



HEART AND BLOOD VESSEL DISEASES 

Many major collaborative and cooperative efforts already exist with Federal and 
non-Federal organizations, professional societies, and the private sector. Exam- 
ples given below include Nutrition; Hypertension; High Blood Pressure Education 
Program: Devices; Emergency Medical Services; Pacemakers and the Artificial Heart; 
Rehabilitation; Cardiac Reconditioning; and Manpower Development. 

• Nutrition. The NHLI is collaborating directly with the U.S. Depart- 
ment of Agriculture (USDA) and the Food and Drug Administration 
(FDA) in defining data gaps and updating and publishing a new 
authoritative nutrient composition source book to supersede a 
previous edition outdated by the new processed and convenience 
foods. Completion of this effort will provide the basic data 
necessary to enumerate dietary constituents for research on the 
effect of diet on blood lipids and heart disease. Information 
received from the FDA on its new voluntary food labeling regu- 
lations and commercial food analyses made by the Grocery Manu- 
facturers of America for the USDA's National Food Data Bank are 
now being channeled directly to the NHLI. 



120 



Hypertension. The National High Blood Pressure Education Program 
has as its major goal the reduction of morbidity and mortality 
from high blood pressure and its sequelae. The NHLI has lead 
responsibility for coordinating this program which is an inter- 
agency, Federal/non-Federal cooperative effort. The Health Ser- 
vices Administration, Health Resources Administration, Food and 
Drug Administration, Veterans Administration, and Department of 
Defense have all designated representatives to the program. 
During the first year of the program, the Veterans Administra- 
tion, Food and Drug Administration, Health Services and Mental 
Health Administration, and National Institutes of Health were 
represented on four Task Forces which made recommendations on 
data base, professional education, community education, and 
national resources and impact assessment. The Department of 
Defense was also represented on the Professional Education Task 
Force. 

Besides representation in the planning effort, several agencies 
took responsibility for implementing some of the Action items 
during the past year. The Health Services and Mental Health 
Administration sponsored the development of mass media educa- 
tional materials; the Food and Drug Administration sponsored a 
workshop on professional education and is sponsoring a survey 
of physicians on high blood pressure; the NHLI sponsored a 
public attitude survey on high blood pressure and a national 
conference on high blood pressure education; and various other 
activities were sponsored jointly by several agencies. 

The program has a policy of cooperating with any organization 
which wants to produce educational materials, and will supply 
technical advice and allow the use of the logo, provided the 
material does not endorse any particular product (s), is not 
for sale, and is factually correct. The response from the pri- 
vate sector has been gratifying. Educational materials for the 
public and the medical professionals have been produced with 
a consistent message. Professional and voluntary organizations 
such as the American Medical Association, American Heart Asso- 
ciation, National Medical Association, American Public Health 
Association, and American Red Cross have endorsed the program. 
The program also cooperates closely with a newly formed group, 
the Citizens for the Treatment of High Blood Pressure. 



High Blood Pressure Education Program: Devices. Hypertension is recognized 
as a significant community health problem. Mass screening pro- 
grams for the detection of hypertension are currently being ini- 
tiated. In view of the needs of these programs, several commu- 
nity groups have asked for guidance in choosing an automated 
device for measuring blood pressure. For this reason the NHLI, 
as the lead agency for the National High Blood Pressure Educa- 
tion Program, has initiated a review of the status of automated 



121 



blood pressure measuring devices with a task force to assess 
these devices. Representatives from the Food and Drug Admin- 
istration and the Veterans Administration are among those help- 
ing in the evaluation. The NHLI will also work with the Amer- 
ican Heart Association through the Committee on Criteria and 
Methods of the Council on Epidemiology. A proposal for evalu- 
ating automated blood pressure measuring devices, as well as 
criteria for a suitable device, has been developed by the Amer- 
ican Heart Association committees. This work will be of great 
help to the NHLI Task Force as it attempts to look at all the 
devices currently available and to assess them in terms of 
suitability criteria. 



Emergency Medical Services. In the fall of 1972, the Secretary of 
Health, Education, and Welfare established an Interdepart- 
mental Committee on Emergency Medical Services with the 
then Health Services and Mental Health Administration assum- 
ing the lead role. The Associate Director for Cardiology, 
Division of Heart and Vascular Diseases, NHLI, was appointed 
the NIH representative. The NHLI has collaborated with the 
Emergency Medical Services Branch of the Health Resources 
Administration on topics of mutual interest and importance, 
including co-sponsorship of the Second National Conference 
on Emergency Health Services and of the meeting on Cardio- 
pulmonary Resuscitation sponsored by the American Red Cross 
and the National Science Foundation. Within the context of 
the National Program, the NHLI will be responsible for the 
elucidation of the pathophysiology of heart disease in its 
earliest emergency phases and for the development of methods 
of care suitable for incorporation into emergency medical 
care systems. 



Pacemakers and the Artificial Heart. Collaborative efforts between the 
Atomic Energy Commission (AEC) and the NHLI date back to 
1965, when the AEC initiated a program for a radioisotope- 
powered cardiac pacemaker with the consultative advice of 
the NHLI. The reliability of these devices, tested in 
animals by the NHLI, has been demonstrated at a level suf- 
ficient to permit clinical implantation in approximately 
50 patients throughout the nation, including several within 
the clinics of NHLI. 

From the inception of the Artificial Heart Program in the 
early 1960's, the NHLI and the AEC have collaborated in deter- 
mining feasibility and exchanging technological information. 
Initial feasibility studies were jointly funded and assessed. 
There has been a renewed and markedly strengthened effort at 
regular scientific interchange and semi-annual formal meet- 
ings between the NHLI and the AEC with respect to artificial 



122 



heart development. Through these contacts and the interchange 
of documents, the NHLI has made available to the AEC recent 
progress and research information on its programs. The AEC, 
in turn, is making available to the NHLI a 33-watt encapsulated 
Plutonium source for conducting important studies. 



Rehabilitation. Coronary artery disease is responsible for chronic 
disease in several million Americans, including 2.5 million 
Americans less than 65 years old. The NHLI has convened a 
task force to study the present state of our knowledge as it 
relates to cardiac rehabilitation. This task force will assess 
the state of the art, the medical and social import of cardiac 
rehabilitation, and present techniques and their scientific 
bases. Recommendations will be developed for clinical imple- 
mentation of what is known and practical, and for initiating 
effective research where necessary. Representatives from com- 
munity and governmental agencies (including the American Heart 
Association, the Council of State Administrators of Vocational 
Rehabilitation, the Rehabilitation Services Administration, 
the Social and Rehabilitation Service) are working closely with 
the NHLI to develop and implement an overall plan on cardiac 
rehabilitation. 



Cardiac Reconditioning. The NHLI is using the results of and collab- 
orating in research and implementation of activities related 
to cardiac functions with the National Aeronautics and Space 
Administration (NASA) . In collaboration with NASA, NHLI is 
evaluating the effects of weightlessness on cardiovascular func- 
tion. Although previous NASA studies of astronauts returning 
from space missions indicate that profound, but apparently 
reversible, changes occur in various bodily functions, the effect 
of prolonged weightlessness on cardiac function is unknown. 
Several observations which suggest that the heart may be affected 
adversely include: (1) necropsy studies on the three Soviet cos- 
monauts who died during re-entry suggested that the heart might 
have undergone severe degenerative changes during their space 
voyage; (2) heart size as determined from frontal X-rays on 
American astronauts have demonstrated the heart to be smaller 
immediately post-flight as compared to pre-flight; (3) pos- 
tural hypotension is an invariable early post-flight finding; 
and (4) NASA scientists have determined that, when compared 
to control pre-flight studies, cardiac output during exercise 
often is markedly reduced shortly after splashdown. 



To follow up on these observations, the NHLI is collaborating 
with the biomedical staff of NASA to systematically evaluate 



123 



the effects of prolonged weightlessness on cardiovascular 
function. Pre- flight studies on the astronauts and back- 
up crew of the Skylab III mission have been completed. 
Post-flight repeat studies are planned. 

Over the past three years, the NHLI has been refining the 
technology of echocardiography and applying this technology 
to the evaluation of patients with all types of cardiac 
disease. Echocardiography is a diagnostic procedure that 
utilizes ultrasound to visualize noninvasively the internal 
structures of the heart. This technique will be used to 
help determine whether prolonged weightlessness leads to 
myocardial atrophy, whether myocardial function is impaired, 
or whether all of the observations to date can be explained 
by a decrease in circulating blood volume. The adequacy of 
baroreceptor-mediated reflexes will also be investigated. 
Finally, by serial measurements over the course of weeks or 
months, these collaborative studies will assess the reversi- 
bility of any abnormalities that develop and the time it 
takes for return to normal function. These studies could 
result in generally applicable information concerning, for 
example, reversibility of certain types of cardiac abnormali- 
ties. 



Manpower Development. As described in the chapter on Manpower 
Development, the NHLI has collaborated with a number of pro- 
fessional and private organizations to conduct an in-depth 
assessment of current manpower status and future needs in a 
variety of disciplines related to the National Program in 
heart and blood vessel diseases. Examples of these organiza- 
tions are the American College of Cardiology, American Associa- 
tion for Thoracic Surgery, and the American Heart Association. 



LUNG DISEASES 

Two major cooperative programs reinforce the Institute's Actions for prevention, 
control, and education activities in smoking and black lung. Other cooperative 
programs relate to structure and function of the lung and to manpower develop- 
ment. These are described below: 



Smoking. Cooperative efforts to reduce smoking and its harm- 
ful effects on health are being conducted with the National 
Cancer Institute (NCI) , National Clearinghouse for Smoking 
and Health, and the Veterans Administration. The goals of 
these efforts are to develop a less hazardous cigarette and 
to study smoking behavior and its modification, and to 



124 



utilize these findings in developing an intervention program 

in the general population. Two specific programs funded jointly 

by NCI and NHLI to achieve these goals are: 

Experiments to Determine Effects of High and Low Nico- 
tine Cigarettes . The purpose of these experiments being 
conducted by the Veterans Administration is to determine 
whether nicotine is involved in the harmful effects pro- 
duced by inhalation of cigarette smoke over many months. 

Comprehensive Smoking Withdrawal Program . This program, 
also funded by the National Clearinghouse for Smoking 
and Health, is designed to conduct a research and demon- 
stration project aimed at developing a community-based 
comprehensive control program which would provide ser- 
vices on an individual referral basis as well as to indus- 
try, civic, and community organizations. 



• Pneumoconioses (Black Lung). Because coal miners are at high risk 
of developing respiratory diseases from exposure to airborne 
dusts, a joint committee, the Working Party on Respiratory 
Diseases Among Coal Miners, has been established, at the 
request of the Governor of Pennsylvania, to define the types 
of efforts most urgently required to prevent or treat work- 
related respiratory diseases. This committee has members from 
Federal (National Institute for Occupational Safety and Health, 
National Institute of Environmental Health Sciences, U.S. 
Bureau of Mines, and NHLI), State (Commonwealth of Pennsylva- 
nia), non-profit (New York Academy of Sciences, American Lung 
Association) , industry (such as U.S. Steel and others) , and 
university organizations. 

The Working Party has four subcommittees: (1) Subcommittee 
on Clinical Problems, with the charge to develop an optimal 
clinical management program, develop simple tests for diag- 
nosis and effectiveness of therapy, and develop specific 
graduate educational and physician education programs; (2) 
Subcommittee on Research Perspectives in Epidemiology and 
Small Airway Disease, with the charge to study small airway 
disease in coal workers and investigate the epidemiology of 
coal worker's respiratory disease; (3) Subcommittee on Research 
Perspectives Concerning Biologically Important Particles in 
Coal Worker's Pneumoconiosis, with the charge to study the 
ultramicroscopic particles in relation to the problem and 
investigate the inactivation of dust in the lungs; (4) Sub- 
committee on Prevention and Treatment of Coal Worker's Res- 
piratory Disease, with the charge to investigate the patho- 
genesis of Progressive Massive Fibrosis and investigate the 
cellular biology approach to the problem. The Working Party 
has scheduled a series of meetings to identify and delineate 
areas for further development and action. 



125 



Pressure and Underwater Biomedical Research. The NHLI is participating in 
a National Cooperative Program of Pressure and Underwater Bio- 
medical Research and Operation Development with the Department 
of the Navy and the National Oceanic and Atmospheric Adminis- 
tration. The objective of this program is to identify criti- 
cal biomedical problems related to respiration and underwater 
pressure and to recommend steps for their solution. The focus 
of the program is on determining alterations in the various 
body systems when responding to increasing physical and physi- 
ological stresses over long periods of time. As one system is 
progressively stressed, e.g., the respiratory system, the ef- 
fects are initially compensated by alterations in other sys- 
tems, e.g., the circulatory or renal systems. As the limit of 
compensatory processes are reached, failure in functions begins 
and may progress to complete failure if the stress continues. 
The respiratory system is the prime target of this research 
which promises to provide important insights into the structure 
and function of the lung. 



Manpower Development. The NHLI has collaborated with the American 
Thoracic Society and the American College of Physicians in 
surveying the national needs for manpower in pulmonary diseases. 
Conclusions drawn from these surveys are presented in the chap- 
ter on Manpower Development. The Institute is also coordinating 
its activities in this area with the American Lung Association 
and other voluntary organizations interested in the implementa- 
tion of the National Program. 



BLOOD DISEASES AND BLOOD RESOURCES 

The National Program in blood diseases and blood resources sets forth a number 
of key research and prevention Actions for ameliorating the effects of sickle 
cell disease, Cooley's anemia, hemophilia, and hepatitis, and for improving the 
management of our nation's blood resources so vital to the treatment of disease. 
Important cooperative efforts relevant to the National Program have been initi- 
ated. Examples of these efforts related to the above Actions are described 
below. 



Sickle Cell Disease. Cooperative efforts between NHLI, the Health 
Services Administration (HSA) , and the Center for Disease 
Control (CDC) are ongoing in this area. Demonstration, screen- 
ing, and education programs have been developed by NHLI and 
HSA. Cooperative efforts have been developed with CDC to carry 
out (1) workshops in hemoglobinopathy detection, (2) a profi- 
ciency testing program for DHEW- funded projects, and (3) the 
establishment of reference laboratories for abnormal hemoglobins. 



126 



• 



Cooley's Anemia. NHLI cooperation with other NIH components, with 
private organizations involved with Cooley's anemia, and with 
the scientific community has led to agreement regarding priori- 
ties for research in this area. 



Hemophilia. The NHLI maintains a cooperative working relationship 
with the National Hemophilia Foundation. Collaborative activi- 
ties include program planning, information exchange, and research. 
The Foundation had significant input into the development of the 
National Program, and discussions are now in progress to assure 
that the programs of the NHLI and the Foundation are complemen- 
tary and mutually supportive of each other. With the assistance 
of the Foundation, the NHLI recently published a pilot study of 
hemophilia treatment in the United States. 



Hepatitis. A Hepatitis Liaison Committee composed of representa- 
tives from all government organizations funding hepatitis research 
has been established to coordinate information exchange and to 
advise all research organizations on program needs and poten- 
tials. This Committee has supported a workshop on the future 
of epidemiologic studies in hepatitis. A Hepatitis Policy Liai- 
son Committee (Bureau of Biologies, NHLI, and National Institute 
of Allergy and Infectious Diseases) coordinates extramural hepa- 
titis research activities funded by the component agencies. 



Blood Resources. The NHLI maintains continuing liaison with the 
three major blood suppliers in the U.S.: the American National 
Red Cross, the American Association of Blood Banks, and the 
Council of Community Blood Centers. These organizations have 
been charged by the Secretary of Health, Education, and Welfare 
to develop implementation plans for a National Blood Policy. 
The NHLI works closely with the Food and Drug Administration 
in regulatory areas relating to safety and efficacy of blood 
products and handling. 

Manpower Development. The NHLI, in cooperation with the National 
Institute of Arthritis, Metabolism, and Digestive Diseases 
(NIAMDD) and the American Society of Hematology (ASH) , has 
drafted a proposal for manpower development in research hema- 
tology in the United States. This proposal was drafted with 
input from a broad segment of the academic hematologic commu- 
nity. 



127 



INTERNATIONAL COLLABORATION 

The disease problems addressed by the National Program are transnational. They 
are major problems encountered by all peoples throughout the world. Implementa- 
tion of the National Program provides a real opportunity for exchange of infor- 
mation between countries on problems of heart, blood vessel, lung, and blood dis- 
eases and blood resources. The planned research and prevention, control, and 
education programs in the United States can be greatly enhanced through coopera- 
tion with other countries which are trying to solve these problems within their 
own borders. Cooperation with other countries enhances and strengthens the capa- 
bility of the Institute for effective national collaboration for the benefit of 
our citizens. During FY 73, the Institute supported 34 foreign projects and 
fellowships in areas related to the National Program. The recently initiated 
US-USSR Health Exchange Program is a highly structured, collaborative interna- 
tional program related to the goals of the National Program. 

In 1956, the National Heart Institute participated for the first time in the 
US-USSR Scientific Exchange Missions. Since that time, American scientists have 
visited research and treatment centers in the Soviet Union and Soviet scientists 
have visited heart research centers in the United States. An expansion of coop- 
eration, including mutual planning and execution of joint research activities, 
between the two countries in the field of health and medical science was agreed 
upon in February 1972. A five-year agreement was signed three months later. 
The cardiovascular area was one of the first three areas recommended for such 
expanded cooperation. The Director of the National Heart and Lung Institute 
is the overall U.S. coordinator for the cardiovascular studies. Key activities 
related to the National Program which are being implemented under this agreement 
are briefly described below: 



Pathogenesis of Arteriosclerosis. Arteriosclerosis is the most common 
type of cardiovascular disease and the chief cause of death 
in both the U.S. and the U.S.S.R. A joint clinical study has 
been undertaken to determine the prevalence in both countries 
of hyperlipidemias and ischemic heart disease, and the effect 
of modifying blood lipids by diet or drugs on the risk of devel- 
oping these diseases. This is the first study of its kind in 
the world. It involves large numbers of well-characterized sub- 
jects in two countries, comprehensively studied according to 
identical techniques based on carefully worked out research pro- 
tocols, and analyzed by highly standardized techniques. 



• Management of Ischemic Heart Disease. Ischemic heart disease is the most 
common clinical complication of arteriosclerosis and the most 
common complication leading to death. The U.S., through the 
NHLI, and the U.S.S.R. are conducting a comparative study of dif- 
ferent approaches for medical and surgical treatment of ischemic 
heart disease. This project, also the first of its kind, will 
evaluate and compare chronic angina and heart attack disability 
treatment methods that have been developed in each country. 



128 



Myocardial Metabolism. This topic involves the study of the activi- 
ties and functions of both the healthy and the diseased heart. 
Thus, it is relevant to the study of all types of heart disease. 
During the past year, American and Russian scientists have 
exchanged information on methods to limit the extent of heart 
muscle damaged by heart attack. These findings will be pub- 
lished jointly. 



Congenital Heart Disease. Congenital heart disease affects an esti- 
mated 25,000 children born in the U.S. each year and a corre- 
sponding number born in the U.S.S.R. each year. The objectives 
of this collaborative study are to develop diagnostic techniques 
and methods of post-operative care, to study the mechanisms of 
development of pulmonary hypertension, to search for new ways 
of reducing mortality from the surgical treatment of tetralogy 
of Fallot, and to study diagnostic techniques and surgical 
treatment of complex heart defects. 



Sudden Death. This problem is a new initiative for collaboration 
in the cardiovascular area. Exchange of information, exchange 
of health professionals, and meetings between Russian and Amer- 
ican specialists are in progress to develop detailed plans for 
scientific cooperation. 



Blood Transfusion, Blood Components, and Prevention of Hepatitis, with Particular 
Reference to Cardiovascular Surgery. This problem is also a new initia- 
tive for collaboration in the cardiovascular area. Exchange 
of information, exchange of health professionals, and meetings 
between Russian and American specialists are being held to 
develop plans for scientific cooperation. 



Technological Development. A joint program in mechanical circulatory 
assistance is under development. 



The actions and schedules for these programs are updated annually by the joint 
US-USSR committee in light of recent progress and future challenges. 



129 



V. MANPOWER DEVELOPMENT 



V. MANPOWER DEVELOPMENT 



The development and maintenance of highly skilled manpower at all levels are of 
great importance in the planning and implementation of our national effort against 
heart, blood vessel, lung, and blood diseases. This is true both from the stand- 
point of the professionals participating in the Program and the public paying for 
and benefiting from the Program. Recruitment, selection, training, development, 
and support of talented young scientists are critical to the continued success of 
the National Program. The search for new solutions to these disease problems will 
make new demands on the nation for adequate numbers of well- trained personnel. 
The scientists, physicians, and allied health professionals engaged in this effort 
must be familiar with many new and complex technologies and must be educated to 
draw experience from old technologies. They must be ready and willing to engage 
in intellectual pursuits which will help in finding new answers. 

The National Heart and Lung Advisory Council, in both its initial Report of April 
1973 and in its first Annual Report of December 1973, places great emphasis on the 
need to develop skilled manpower. This is needed not only to replace losses from 
the present pool through attrition, but also to search for innovative approaches 
to the disease problems addressed by the National Program. The NHLI Summary of 
May 1973 recognized the importance of manpower development. However, the Insti- 
tute's position was that any specific recommendations should be keyed to documented 
needs in specific areas. Therefore, recommendations were deferred at that time, 
pending results of a major review of manpower needs in those disciplines that 
affect implementation of the National Program. 

In considering the manpower needs for the expanded national effort, three factors 
must be given careful consideration: 

• Manpower development, research, and health care are three 

segments of an interrelated continuum, and manpower develop- 
ment cannot be considered separately from research or health 
care any more than research per se can be considered separately 
from health care. 



131 



Manpower development needs will continue to grow as the store 
of knowledge (now doubling every ten years) grows through 
research, as the population grows, and as the public demands 
new and increasingly sophisticated approaches to health care. 



There is an increasing demand for public accountability of 
all health professionals, since the public is the source of 
funds as well as the ultimate beneficiary of manpower devel- 
opment, health research, and health care. Thus, the public 
must be given confidence that every effort is being made to 
assure high quality of professional performance throughout 
the program — in planning, research, prevention, education, 
control, evaluation, and coordination. 



Data so far collected indicate the positive need for a vigorous manpower devel- 
opment program for the advancement of future research and investigation. This 
is based on analysis of a number of surveys and assessments by Institute staff, 
members of the National Heart and Lung Advisory Council, voluntary agencies, 
and professional organizations. The estimates below are conservative and were 
derived by assessing: 

• The minimum number of research investigators needed for 
the maintenance of selected, vital research activities 

• The minimum number of trained investigators currently 
needed to fill documented and budgeted faculty vacancies 
directly related to the mission of the NHLI 

• The particular talents, disciplines, or areas that need 
additional manpower for implementing a vigorous National 
Program . 



HEART AND BLOOD VESSEL DISEASES 



There are approximately 11,000 active cardiologists in this country, with a con- 
siderable variation in geographic distribution. In a recent survey, fully 5 per- 
cent of the active cardiology training programs had no full-time faculty member. 
Furthermore, almost 30 percent of the training programs had an average of two 
staff positions that were budgeted but unfilled, representing a national total of 
150 to 180 positions in this category. A separate survey revealed that only 94 
medical centers in the United States had certified pediatric cardiologists on 
their staffs, representing a shortage of approximately 100 pediatric cardiologists 
in this country. Taking annual losses into account, it is estimated that 350 to 
400 individuals would have to be added to the research manpower pool each year 



132 



merely to maintain the present status of heart and blood vessel research efforts. 
Thus, the Institute estimates that, at a minimum, approximately 600 individuals 
should be enrolled in fellowship or trainee programs related to heart and blood 
vessel diseases in order to maintain the present level and to implement the Action 
items in the National Program. 

• The NHLI proposes to place special emphasis on training in 
those areas in which research skills are currently in short 
supply, namely: pediatric cardiology, behavioral and moti- 
vational disciplines, bioengineering (with a particular view 
to improving noninvasive diagnostic instrumentation) , genetics 
(as related to a variety of disease states such as hyperten- 
sion and abnormal lipid metabolism) , pediatric nutrition and 
metabolism (as related to lipid metabolism) , microcirculation 
(including aspects of blood flow and tissue metabolism) , 
immunochemistry, and epidemiology and biostatistics. 



LUNG DISEASES 

A recent survey of professional manpower revealed that 130 currently funded but 
unfilled vacancies exist on medical school faculties in lung diseases and at 
least 20 additional vacancies exist at research institutes. It is estimated that, 
within the next two to three years, approximately 550 well-trained individuals will 
be required for the staffs of medical schools and research institutions engaged in 
lung disease activities. 

Research in the pulmonary disease area has now developed special and almost unique 
requirements. Increasingly, it has become possible to study lung diseases by 
investigation of underlying mechanisms, and physicians and scientists must now 
draw upon fundamental disciplines that are comparatively new to the lung field, 
such as biochemistry, cell biology, immunology, and bioengineering. 

Because of the great need for interdisciplinary research and training in the lung 
diseases area, the Institute plans to give high priority to such programs. To 
date, basic scientists have not been conversant with the problems of lung diseases, 
and pulmonary clinicians have been generally uninformed about the basic studies 
that might contribute to their research. 

• The NHLI believes that for these special interdisciplinary 
research training programs, where new and basic contribu- 
tions can be made, between 150 and 200 research fellows 
should be supported in the immediate future. 



133 



BLOOD DISEASES AND BLOOD RESOURCES 



Two separate studies of staff positions in academic hematology, focusing upon 
institutions with academic programs in blood diseases and blood resources, re- 
vealed that about 10 percent of the positions in academic hematology are unfilled. 
Research areas with the largest number of unfilled positions included hemoglobin- 
opathies, coagulation, immunohematology, and blood banking — all areas of major 
concern in the National Program. 

The development of manpower for blood banking is one of special urgency in the 
United States. Not only is there a lack of adequately trained manpower in blood 
banking, but there are also insufficient training faculties and resources. These 
limitations have prevented the effective application of newer techniques and 
knowledge in this area of health care vital for the American people. 



The Institute estimates that approximately 200 research 
fellows should be trained now in the blood research areas 
addressed by the National Program. The efforts in this 
regard will be coordinated with other Institutes of the 
NIH involved in hematology manpower development. The 
areas of special need include: blood banking, platelet 
function and abnormalities, thrombosis in the microcircu- 
lation, thromboembolism, abnormal hemoglobins including 
sickle cell disease, red blood cell membranes and enzyme 
systems, and the biology of transplantation of tissues 
and organs . 



Since the training required in all of the above areas is highly specialized, it 
will take several years or more before the individuals enrolled in the programs 
will be ready to contribute fully to the activities of the National Program. 
Prompt initiation of these manpower development programs is of major importance. 
Otherwise, implementation and progress of the National Program will be impeded. 



134 



VI. IMPLEMENTATION OF OTHER PROVISIONS OF THE ACT 



VI. IMPLEMENTATION OF OTHER PROVISIONS OF THE ACT 



The passage of the National Heart, Blood Vessel, Lung, and Blood Act of 1972 sig- 
nificantly expanded the Institute's mandate and responsibilities. To implement 
the new and increased activities authorized by the Act in an efficient and timely 
manner, the National Heart and Lung Institute has made significant changes in its 
organizational structure, program management, and ways of communicating and col- 
laborating with the public and the professional community in the National Program. 
Five areas of special importance to the successful implementation of the National 
Program are discussed in this chapter: 



National Research and Demonstration Centers 

Construction 

Mechanisms of Support 

Administrative Changes 

Program Review and Evaluation. 



NATIONAL RESEARCH AND DEMONSTRATION CENTERS 



P.L. 92-423 states that the Director of the Institute may provide for the develop- 
ment of National Research and Demonstration Centers: up to 15 Centers for problems 
related to heart, blood vessel, and blood diseases, and up to 15 Centers for prob- 
lems related to chronic lung diseases. The purpose of the Centers' program is to 
facilitate and expedite the translation of research results to clinical practice 
in local communities across the nation. The Legislative Act specifies that the 
programs of such Centers would encompass basic and clinical research into, train- 
ing in, and demonstration of, advanced diagnostic, prevention, and treatment methods 
for the respective diseases. In the initial" National Plan, the NHLI proposed to 



135 



establish approximately five Centers in FY 74 and an additional five in FY 75, 
at an initial level of about $1 million per Center in the first year, rising 
incrementally to about $3 million per Center in the third year. After further 
study and on advice of the National Heart and Lung Advisory Council, we now 
estimate the initial operational cost per Center at approximately $3 million 
per year. 

A Program Announcement and Guidelines, developed with advice from the National 
Heart and Lung Advisory Council, were released in August 197 3. A National 
Research and Demonstration Center is defined as a national resource attached to 
a major medical complex and dedicated to working in close collaboration with the 
Institute to further the goals of the National Program. A Center preferably 
should focus on one major area — heart and blood vessel diseases, lung diseases, 
blood diseases, or blood resources. However, a combination of areas would be 
acceptable if shown to be more effective in meeting the goals of the National 
Program. The guidelines require that each Center must include programs in fun- 
damental research, clinical research and clinical application, an environment 
conducive to the training of young scientists, and an information and education 
program. 

A meeting of potential applicants was held at the National Institutes of Health 
early in October 1973. More than 300 representatives from interested institu- 
tions attended and NHLI staff answered questions and clarified specific aspects 
of the program. Approximately 7 5 letters-of -intent to apply have been received: 
31 in heart and blood vessel diseases, 21 in lung diseases, 15 in blood, 5 com- 
bining heart and lung diseases, and a few not classified. Formal applications 
are due early in 1974. 

Proposals for the Centers will be reviewed in the spring of 1974 by panels of 
expert consultants and by the National Heart and Lung Advisory Council. The 
ability of the Institute to make any awards for National Research and Demonstra- 
tion Centers is contingent upon the availability of appropriated funds. The 
Institute plans to activate the program early in FY 75. Additional Centers may 
be activated in the future as the effectiveness of the first group is determined, 
and as experience is gained in the planning, monitoring, and execution of these 
multidisciplinary programs. 



CONSTRUCTION 



The National Heart and Lung Advisory Council, in its first Annual Report, reit- 
erates the need for funds for construction of facilities to develop the required 
capabilities for full implementation of the National Program. This is particu- 
larly true for the National Research and Demonstration Centers. Funds for con- 
struction are not included in the NHLI fiscal allocation plan for FY 74. There- 
fore, initial Centers must provide for all facilities and resources necessary 
to initiate the program. However, the Centers will serve as national resources 
for expediting the transfer of research results to national clinical practices, 



136 



and additional facilities will be needed as each Center becomes fully opera- 
tional. In the initial NHLI Plan, the Institute estimated the net space require- 
ments of each Center as approximately 80,000 to 100,000 square feet, and further 
estimated that approximately 60 percent of this space might have to be newly 
constructed. Projections are included in the budget for 450,000 square feet 
in FY 76, 225,000 square feet in FY 77, and 225,000 square feet in FY 78 to pro- 
vide for new construction for the Centers, and an additional 60,000 square feet 
for other specialized research facilities for the National Program. These esti- 
mates are based on the establishment of 15 Centers, each with a space requirement 
of approximately 100,000 square feet, and assuming that the government will pay 
for the 60 percent which is newly constructed. 

A long lead time for planning and executing construction projects is not unusual. 
Therefore, the Institute again recommends that funds appropriated for this pur- 
pose remain available through the year subsequent to the one in which they are 
appropriated, with the proviso that they be used for construction only. 



MECHANISMS OF SUPPORT 

Implementation of the programs of research and prevention, control, and education 
that collectively make up the National Program involves the participation of a 
broad range of biomedical professionals. Support is provided through a variety 
of mechanisms. As outlined in the initial NHLI plan, these mechanisms range 
from the traditional research project grant, for the independent investigator 
who wishes to contribute to the National Program by carrying out relevant research 
according to a plan initiated by himself, to highly structured research contracts, 
for investigators who wish to participate in programs which are addressed to 
sharply targeted goals and solicited and monitored by the Institute. Between 
these two mechanisms are larger multidisciplinary programs, such as the current 
Specialized Centers of Research and the proposed National Research and Demonstra- 
tion Centers. These multidisciplinary efforts, although grant-supported, com- 
bine a degree of investigator independence with mission-orientation and a close 
working relationship with the Institute in order to integrate the efforts of one 
Center with the activities of other Centers and with those of the Institute. 

The Institute will continue to use the fiscal mechanisms most appropriate to 
given activities. Independent research must continue and be fostered as a major 
source of new and fresh ideas for scientific advance. At the same time the 
Institute has a responsibility to society to facilitate the transfer of these 
scientific advances to the American health care system. Table 3 shows the allo- 
cation of funds between grants and contracts in FY 73. We would expect that 
the distribution of funds among these mechanisms will remain substantially 
unchanged in FY 74. The Institute does not plan any significant change in this 
ratio of distribution in the near future. The Intramural Research noted in the 
table is the in-house program of basic and clinical research carried out at the 
National Institutes of Health. 



137 



Table 3. NHLI Resource Allocation by Major Activity 



Activity 


Percent of Funds 


FY 1973 


Research Grants 

Training Grants and Fellowships 

Research Contracts 

Intramural Research 

Research Management and Program Services 


54.8 
8.9 

24.0 
7.6 
4.7 


TOTAL 


100.0% 



ADMINISTRATIVE CHANGES 



During the past year, the National Heart and Lung Institute has made four major 
administrative changes: 



• Reorganization of the Institute 

• Appointment of an Assistant Director for Health Information 
Programs 

• Creation of an Office of Prevention, Control, and Education 

• Expansion of the National Heart and Lung Advisory Council. 



The Institute's activities during the past three years have broadened to include 
additional programs in lung and blood diseases, demonstration and control respon- 
sibilities, and additional program-oriented efforts, such as National Research 
and Demonstration Centers. In line with these program changes, the NHLI examined 
its basic organization and concluded that the Institute had developed to a stage 
where the primary organization should be mainly by subject matter rather than 
by mechanism of support. Consequently, the Institute has been reorganized into 
five divisions: Division of Heart and Vascular Diseases, Division of Lung Dis- 
eases, Division of Blood Diseases and Resources, Division of Intramural Research, 
and Division of Extramural Affairs. 



138 



The National Heart, Blood Vessel, Lung, and Blood Act authorizes the Director 
of the Institute to appoint an Assistant Director for Health Information Pro- 
grams responsible for disseminating health information with particular emphasis 
on risk factors and preventive measures. The Act also authorizes the Director 
to establish Prevention, Control, and Education Programs for Heart, Blood Vessel, 
Lung, and Blood Diseases. Both provisions have been implemented. The Assistant 
Director for Health Information Programs heads the newly activated Office of Pre- 
vention, Control, and Education which is responsible for the prevention and con- 
trol programs outlined in Chapter III of this report. The first programs under 
its aegis are already operational and relate to hypertension and to sickle cell 
disease. 

The Act considerably expands the National Heart and Lung Advisory Council, both 
in membership and in responsibilities. In addition to developing its own Annual 
Report on the National Program, the Council plays an active role in development 
of the Institute's long-range program plans. The Act authorizes appointment of 
an Executive Secretary of the Council to assist the membership as needed. This 
position has been filled by a member of the professional staff of the Institute. 



PROGRAM REVIEW AND EVALUATION 



Approximately 300 biomedical specialists were involved in developing the National 
Program in heart, blood vessel, lung, and blood diseases and blood resources less 
than a year ago. Since that time, the activities of the National Program have 
been extensively reviewed and evaluated. Program goals, progress, challenges, 
actions, and schedules have been examined in terms of their relative importance 
to the overall program. As a result of this review process, a revised program 
structure was developed and changes were made in program direction (as set forth 
in Chapter III) . These revisions form the basis for this annual report and updated 
5-year Plan. Review and evaluation continues at each level of the Institute's 
programs and will continue to form the basis for each Annual Report of the Director 
and each annual updating of the 5-year Plan. 

Furthermore, in implementing the program strategy (outlined in Chapter I) , the 
Institute will review and evaluate each program as activities move in an ordered 
sequence from research to testing to application. Programs will be reviewed both 
before and after application in health care delivery systems. The Institute is 
developing procedures for ensuring that these review processes are both appro- 
priate and effective. 

In addition, a number of specific evaluation efforts are underway or planned. 
These studies involve the effectiveness of Specialized Centers of Research pro- 
grams, the effectiveness of contract programs in lung diseases and the Pulmonary 
Academic Award Program, rehabilitation of the patient after myocardial infarction, 
management of the national blood resource, assessment of the status of left heart 
assist devices, and the role of cultural factors in the development of heart and 
blood vessel diseases. 



139 



An Artificial Heart Assessment Panel was convened to assess the economic, ethi- 
cal, legal, medical, psychiatric, and social implications of clinical applica- 
tion of a totally implantable artificial heart. The recommendations of this 
Panel have been submitted to the Institute and will be considered in future 
program developments. 

Several studies of manpower availability have been supported in order to deter- 
mine the manpower needs in various areas related to the National Program. These 
studies are discussed in Chapter V in this report. Training opportunities and 
manpower needs will be continually reviewed by the Institute since these factors 
will play a vital role in implementing the 5-Year National Plan. 



140 



VII. RESOURCE ALLOCATION PLAN 



VII. RESOURCE ALLOCATION PLAN 



The problems of heart, blood vessel, lung, and blood diseases represent both 
an indictment and an opportunity for action. As stated in Chapter I, "The 
United States, despite its high state of technology, lags behind many other 
Western nations in the health of its citizens. In fact, it ranks 24th in the 
world with respect to life expectancy for men. The high mortality from heart 
and blood vessel diseases is the major contributing factor to this shortened 
life expectancy." The National Heart, Blood Vessel, Lung, and Blood Program 
is an effort to correct these problems. It will require revision of national 
priorities and redistribution of resources to better serve the health needs of 
the American people. 

In developing this report, the Institute has taken a hard look at ways in which 
the quality and comprehensiveness of the National Program can be improved. It 
has reexamined the priorities within each program area, developed plans to shift 
resources to more productive use, and revised its planned course of action over 
the next five years accordingly. Specifically, the NHLI has reviewed: 

• The needs and opportunities for research, prevention, 
control, and education in heart, blood vessel, lung, and 
blood diseases and blood resources. (See Chapter III.) 

• The real challenge of coordinating national efforts in 
these areas. (See Chapter IV.) 

• Related manpower development requirements. (See Chapter V.) 

• Facilities and mechanisms of support needed for implementa- 
tion of the National Program. (See Chapter VI.) 

This program review and evaluation has focused on national priorities and 
health needs of the American people. Program requirements have been devel- 
oped within this framework by key personnel in the National Heart and Lung 
Institute with the advice of the National Heart and Lung Advisory Council. 
Our priority actions are described in earlier chapters of this report, and 
the resources needed to fulfill these NHLI-supported actions are presented 
here. Contributions to the National Program by non-NHLI-supported activities 
are not included in these resource projections. 

141 



FISCAL SUMMARY AND PROJECTIONS 

\ 

The resource projections discussed in this section are based on scientific and 
professional judgement as to the resources required to accomplish program objec- 
tives within the time frame indicated. However, it is recognized that the allo- 
cation of national resources to execute the program must be determined in rela- 
tionship to other competing national needs at any given time. 

Acting upon the results of its program review and evaluation, the Institute has 
revised and updated the fiscal projections presented in the initial National 
Heart, Blood Vessel, Lung, and Blood Program (Volume I) in May 1973. The major 
reasons for these revisions are: 



• Program monitoring and evaluation of research programs has 
resulted in identification of both expanded and reduced 
opportunities and needs in some program action areas. (See 
section on Research in Chapter III.) 

• As indicated in Chapter II recent research findings have 
opened potentially new vistas which require exploration of 
new initiatives. 

• Research and prevention, control, and education pilot program 
results have suggested or proven the need for and capability 
of expanding our prevention, control, and education programs. 
(See section on Prevention, Control, and Education in Chapter 
III.) 

• Recently completed studies have provided us with a clearer 
insight into both manpower and facilities requirements. 
(See Chapters V and VI.) 

The projected resource estimates for FY 76 to FY 80 are shown in Table 4. This 
projection is provided so that the planning process will stay in phase with the 
overall departmental planning and budgeting cycle. The table, organized accord- 
ing to the program activity categories discussed earlier in this report, provides 
fiscal projections for: 

• Extramural research programs in heart and blood vessel diseases, 
in lung diseases, and in blood diseases and blood resources. 
Research allocations are also shown for each subprogram within 
these major disease categories. 

• Continued implementation of special NHLI programs authorized 
by Public Law 92-423: the National Research and Demonstration 
Centers; Prevention, Control, and Education Programs; and 
construction of facilities. 



142 



Table 4. Projected Resource Allocations* for the National Heart, Blood Vessel, Lung, and Blood Program 

FY 76 -FY 80 
(Dollars in Millions) 







Fiscal Years 




Program Activities 
























1976 


1977 


1978 


1979 


1980 


Extramural Research Programs 












Heart and Blood Vessel Diseases 












Arteriosclerosis 


$ 57.20 


$ 58.40 


$ 60.40 


$ 62.40 


$ 60.10 


Hypertension 


31.20 


32.20 


33.30 


33.80 


32.30 


Cerebrovascular Disease 


3.80 


3.90 


4.00 


4.10 


4.10 


Coronary Heart Disease 


42.50 


43.50 


46.10 


47.30 


44.80 


Peripheral Vascular Diseases 


4.10 


4.20 


4.30 


4.40 


4.40 


Arrhythmias 


16.50 


17.20 


19.00 


19.20 


18.20 


Heart Failure and Shock 


20.60 


21.30 


23.60 


24.90 


23.70 


Congenital and Rheumatic Heart Diseases 


9.60 


9.90 


10.40 


10.60 


10.60 


Cardiomyopathy and Infections of the Heart 


3.80 


3.90 


5.20 


6.50 


7.00 


Circulatory Assistance 


19.90 


20.90 


23.90 


30.90 


34.80 


Subtotal Heart and Blood Vessel Diseases 


209.20 


215.40 


230.20 


244.10 


240.00 


Lung Diseases 












Structure and Function of the Lung 


7.70 


8.00 


8.60 


9.20 


8.80 


Pediatric Pulmonary Diseases 


10.30 


10.80 


11.20 


12.00 


11.50 


Emphysema and Chronic Bronchitis 


8.40 


8.90 


9.80 


10.30 


10.60 


Fibrotic and Immunologic Lung Diseases 


8.50 


9.00 


9.10 


10.50 


10.90 


Respiratory Failure 


7.10 


7.20 


7.60 


8.00 


8.00 


Pulmonary Vascular Diseases 


2.20 


2.30 


2.50 


2.30 


2.00 


Inhalation Diseases 


2.20 


2.60 


3.00 


2.50 


2.00 


Respiratory Assistance 


.80 


1.00 


1.20 


1.20 


1.20 


Subtotal Lung Diseases 


47.20 


49.80 


53.00 


56.00 


55.00 


Blood Diseases and Blood Resources 












Bleeding and Clotting Disorders 


19.54 


20.08 


19.98 


19.73 


18.03 


Sickle Cell Disease and Related Disorders of 












the Red Blood Cell 


18.05 


18.77 


19.44 


20.32 


19.32 


Blood Resources 


14.81 


14.95 


17.18 


19.65 


18.65 


Biomaterials 


3.10 


4.00 


4.20 


4.20 


4.00 


Subtotal Blood Diseases and Blood Resources 


55.50 


57.80 


60.80 


63.90 


60.00 


National Research and Demonstration Centers 


25.25 


48.50 


55.20 


56.70 


58.70 


Prevention, Control, and Education Programs 


31.80 


38.30 


39.00 


37.50 


38.30 


Construction 


60.00 


30.00 


30.00 


— 


- 


Manpower 


20.80 


20.80 


21.90 


22.70 


22.70 


Intramural Research Programs 


25.00 


26.00 


26.00 


26.00 


27.00 


Research Management and Program Services 


21.66 


25.16 


23.67 


24.69 


24.43 


TOTAL 


$496.41 


$511.76 


$539.77 


$531.59 


$526.13 


'This tabulation gives the primary thrust of activities, e\ 


en though 


these act 


vities gens 


;rally 




involve more than one subprogram. 













143 



• NHLI ' s Intramural Research Programs, Manpower Development 
Programs, and Research Management and Program Services. 



The resource allocations presented in Table 4 are consistent with the program 
activities projected and discussed in Chapters III, IV, V, and VI of this report. 
These allocations have been distributed in such a way as to build on past accom- 
plishments and to anticipate future opportunities in specific program areas. 
In accordance with the legislation, at least 15 percent of the fiscal resources 
are projected for diseases of the lung and at least 15 percent toward the prob- 
lems of blood diseases and resources. 

It is important to point out that the projected resource allocations give the 
primary thrust of activities , even though these activities generally involve 
more than one subprogram, with some activities fundamental to many subprograms. 
Since subprograms cannot be made mutually exclusive, the allocation of a given 
project may be somewhat arbitrary. For example, a project involving the effects 
of arrhythmias in coronary heart disease upon heart failure would be categorized 
according to its primary thrust. A project on the movement of ions across cell 
membranes, which is fundamental to the causation and prevention of arrhythmias 
and heart failure and is applicable to all forms of heart disease and even to 
symptoms of cerebrovascular disease, would be allocated to multiple categories. 

The fiscal requirements for the National Program total approximately $496 mil- 
lion in FY 76, an increase of $91 million over the previously recommended budget 
for FY 76. These requirements will increase incrementally to $540 million in 
FY 78; in FY 79, construction funds will not be required and the budget will 
decline to $532 million, followed by a subsequent reduction to $526 million in 
FY 80. The rationale for increased resource projections for certain programs 
in the 5-Year Plan was delineated in earlier sections of this report; however, 
we summarize in the following paragraphs the proposed program actions which 
require overall budget increases in the revised estimates projected here for 
FY 76 through FY 80. Figure 2 gives a comparison of the projected resource 
allocations for the Program in the 1973 and 1974 NHLI plans. It should be 
emphasized that resource projections have not been adjusted upward for infla- 
tionary increases since the 1973 plan was prepared. Similarly, the projections 
for fiscal years 1976 through 1980 are based on 1973 estimates of the costs of 
accomplishing program objectives. 

There has been no change in the total projected estimates for the Extramural 
Research Programs in Heart and Blood Vessel Diseases, Lung Diseases, and Blood 
Diseases and Blood Resources. However, there have been internal readjustments 
of resources among subprograms in each of these program areas, reflecting revised 
priorities, new opportunities for action, and redistribution of resources to new 
programs. The total estimates for the NHLI ' s Intramural Research Program remain 
the same. Increased budget estimates have been projected over the next five 
years for the following extramural programs: Arteriosclerosis, Hypertension, 
Cerebrovascular Disease, Arrhythmias, Circulatory Assistance, Structure and Func- 
tion of the Lung, and Pediatric Pulmonary Diseases. 



144 



Authorization 


FY 73 = 


$400 M 


FY 74 = 


$460 M 


FY 75 = 


$520 M 



National Heart & Lung 
632_ Advisory Council Report 
--^* December 1973 



National Heart & 
Lung Advisory 
Council Report 
April 1973 



Updated NHLI 
5- Year Plan, 
1974" 



Initial NHLI 5 Year 
Plan, 1973* 




650 



600 



550 



o 

a 500 



z 450 

o 

_l 

g 400 

350 

300 



76 77 

FISCAL YEAR 

"Does not include Research Management and Program Services, estimated at 4.87% of total estimated program costs. 
"Includes Research Management and Program Services. 

Figure 2. Comparison of Projected Resource Allocations for the 
National Heart, Blood Vessel, Lung, and Blood Program (FY 73 Through FY 80) 

Although the fiscal projections for the remaining extramural subprograms 
represent decreases or no change since last year's projections, most of these 
programs will increase through FY 79, and decline in FY 80, in accordance with 
projected activities. Circulatory Assistance and Biomaterials , which were 
included under other subprograms in last year's Plan, have been given separate 
status in the revised Plan. The addition of three new program areas in lung 
diseases is balanced by a reduction in other areas of lung diseases. Two of 
these new areas are projected to increase slightly through FY 78 and decline 
thereafter through FY 80; the third, Respiratory Assistance, will grow gradually 
between FY 76 and FY 80. No major revisions have been made in the projected 
resource allocations for blood diseases and blood resources in FY 76, and grad- 
ual increments are currently projected in these areas between FY 76 and FY 79, 
closely following the projections in the initial Plan. The Intramural Research 
Program is, similarly, projected to gradually increase between FY 76 and FY 80 
at the levels projected last year. 

Five of the program activity areas listed in Table 4 account for the entire 
increase in the total revised resource allocation recommended for FY 76, as 
well as for the total budget increases projected from FY 76 through FY 80. 
These areas are: National Research and Demonstration Centers; Prevention, 
Control, and Education Programs; Construction; Manpower; and Research Manage- 
ment and Program Services. Among these five expanding areas, it is currently 
projected that construction funds will be required in fiscal years 1976, 1977, 
and 1978. Research Management and Program Services, which were not included 
in the May 1, 1973, estimates, account for about $22 million of the $91 million 
increase in the FY 76 projected estimates. 



145 



Within the overall fiscal limitations identified above, the major increases that 
have been projected in the revised fiscal allocations are required in order to 
support heightened program activity in each area. Key aspects of these activities 
are summarized as follows: 



Arteriosclerosis. Research has provided significant new knowledge 
about the causes and development of arteriosclerosis. Current 
research supports the feasibility of early diagnosis (including 
at birth) ; expanded programs are required to evaluate these 
research opportunities. The relationship of genetic factors to 
the development of arteriosclerosis is strongly suggested; 
increased human and animal studies are needed to determine the 
exact role of these factors. Special multiple intervention 
clinic programs for populations at high risk will be initiated. 
A US-USSR cooperative risk factor study will be implemented. 
(For further discussion, see Arteriosclerosis under Research in 
Chapter III.) 



Hypertension. Building on research advances in the genesis of 
hypertension, a pilot clinical trial for therapy of mild hyper- 
tension is proposed. Emphasis will also be expanded on new drug 
formulations to control hypertension. Hypertension detection 
and follow-up programs will be continued to determine the effec- 
tiveness of therapy. (See Hypertension under Research in 
Chapter III.) 



Cerebrovascular Disease. Animal studies will be initiated to deter- 
mine the contribution of chronic arteriosclerosis and hyper- 
tension to stroke from brain hemorrhage. Other programs will 
be continued. (See Cerebrovascular Disease under Research in 
Chapter III.) 



Arrhythmias. Fundamental research programs will be expanded to 
increase our understanding of arrhythmias in order to pre- 
vent those which cause sudden cardiac death. Expanded activ- 
ities will focus particularly on the electrophysiology and 
therapy of rhythm disturbances, on clinical studies to iden- 
tify chronic or intermittent disturbances, and on the devel- 
opment of techniques for analyzing electrocardiographic 
rhythm signals. (See Arrhythmias under Research in Chapter 
III.) 



Circulatory Assistance. The majority of activities in this program 
area are continuations formerly classified in other program 
areas, primarily heart failure and shock. Expanded efforts 
will include development of heart assist and replacement 
devices. (See Circulatory Assistance under Research in Chap- 
ter III.) 



146 



Structure and Function of the Lung. Recent research advances at the cell- 
ular level hold great promise for understanding the mechanisms 
involved in the development of lung diseases. Individual and 
collaborative research efforts will be expanded in order to 
build on these advances. (See Structure and Function of the 
Lung under Research in Chapter III.) 



Pediatric Pulmonary Diseases. Recent important breakthroughs have 
occurred which make possible effective detection and therapy 
of hyaline membrane disease. Plans are being developed for 
improved management of hyaline membrane disease through pro- 
grams for rapid transfer of infants with this disease to 
intensive care units. Programs will be initiated for improved 
treatment of cystic fibrosis and long-term follow-up of chil- 
dren with bronchiolitis. (See Pediatric Pulmonary Diseases 
under Research in Chapter III.) 



National Research and Demonstration Centers. The Centers will provide an 
important mechanism by which the Institute can assure that 
the advances gained through research are translated to improved 
health care in the community. (See Chapter VI.) 



• Prevention, Control, and Education Programs. Major program emphases discussed 
in Chapter III which will necessitate increased support are as 
follows: 

Hypertension information and education programs 

Community hypertension control demonstration projects 

Increased nutrition and other risk factor detection and 
prevention efforts related to arteriosclerosis 

- Collaborative emergency care and rehabilitation programs 
related to coronary heart disease 

Early recognition and treatment demonstration programs 
for cardiac and respiratory diseases of the newborn 

Professional and public educational programs concerning 
avoidance of noxious dust, vapors, or gases 

Collaborative education programs related to smokers 

Education programs for sickle cell disease and Cooley's 
anemia 

Screening and education clinics for sickle cell disease 



147 



Education programs in hemophilia 

Hepatitis epidemiology and control programs 

Evaluation of technical, social, ethical, and legal prob- 
lems associated with organ transplantation 

Professional education regarding optimal use of blood 
resources . 



Construction. Construction of appropriate and adequate facilities 
will be important to the planned increases in program activity. 
The projected establishment of National Research and Demonstra- 
tion Centers in FY 75 particularly requires that additional 
funds be available. (See Chapter VI.) 



Manpower. Funds for the development and maintenance of highly 
skilled manpower are necessary in order to ensure that well- 
trained scientists, physicians, and allied health professionals 
will be available to assume the increased responsibilities 
inherent in the implementation of a National Program. (See 
Chapter V.) 



NHU STAFF ALLOCATION PLAN 



The Act also requires that the Plan for the National Program include a statement 
regarding the NHLI staffing needs for implementing the Program. The Institute 
Summary of May 1973 included such a statement, noting that there were 626 autho- 
rized positions for the NHLI at that time and projecting a need for 764 positions 
in FY 74. As of February 13, 1974, the authorized ceiling for the NHLI is 664 
positions. By judicious use of manpower resources, the Institute has been able 
to initiate activity in several areas in response to the provisions of the Act. 
Examples, discussed in more detail in other chapters of this report, are cited 
briefly below: 

• Appointment of an Executive Secretary for the National Heart 
and Lung Advisory Council 

• Provision of staff assistance to the Council in its expanded 
role, particularly in the areas of program planning and prep- 
aration of the Annual Report of the Council 



• 



Updating of the National Program Plan and development of this 
Annual Report of the NHLI 

Organization of the Interagency Technical Committee and staff 
to provide support for its coordinating role 



148 



• Establishment of an Office of Prevention, Control, and Educa- 
tion and planning for prevention, control, and education 
programs in several areas 

• Development and distribution of a Program Announcement and 
Guidelines for National Research and Demonstration Centers, 
with first competition for awards underway. 



To initiate these programs, the Institute has conserved manpower in a number of 
ways. One was to abolish the Division of Technological Applications and divide 
its activities among the three categorical scientific divisions. Another way 
was to centralize the review function for programs supported by the contract 
mechanism. A third way was to consolidate some of the intramural activities. 

In addition to the above efforts the scientific divisions of the NHLI have for- 
mulated plans and begun implementing the Action items in the National Program: 

• The Division of Heart and Vascular Diseases will establish 
Specialized Centers of Research (SCOR) in Ischemic Heart Dis- 
ease; bring up to full strength the ongoing clinical trials 
in the areas of risk factor modification, lipid metabolism, 

and hypertension; expand work on cardiovascular devices, includ- 
ing circulatory assist pumps and noninvasive means for diagnos- 
ing heart and blood vessel diseases; and stimulate increased 
activity in fundamental and clinical research. 

• The Division of Lung Diseases will expand programs that apply 
the fundamental scientific disciplines to research on the nor- 
mal and diseased lung; initiate and expand epidemiological 
studies; initiate education and control programs; and expand 
efforts related to development of life-saving respiratory assist 
devices. The pace of research in lung diseases, long lagging, 
is only now entering a phase of rapid acceleration. 

• The Division of Blood Diseases and Resources will expand 
the hemophilia program; take advantage of recently acquired 
knowledge regarding hepatitis and expand the hepatitis 
program; stimulate basic and clinical research in bleeding 
and clotting disorders; and play a major role in the develop- 
ment of the Nationwide Blood Program. 

• The Division of Intramural Research will expand laboratories 
devoted to lung diseases (only recently established) , the 
molecular basis for sickle cell disease and Cooley's anemia, 
and the molecular basis for certain lipid abnormalities. 

• The Division of Extramural Affairs, responsible for initial 
review of proposals in many of the above areas, of necessity 
will have to expand as the demand for its services increases. 



149 



To operate the National Program effectively, the NHLI will need additional 
staff — at the middle and upper professional levels as well as in support posi- 
tions. Programs such as disease prevention, control, and education, and com- 
prehensive centers are new to the Institute. Their review and administration 
will require staff with knowledge and skills new to the Institute. 

Over the years, authorized ceilings for staff for the NHLI have not kept pace 
with appropriations. In the five years preceding the enactment of Public Law 
92-423, the appropriation increased by 38 percent: from $168 million in FY 68 
to $232.6 million in FY 72. In the same period, the number of authorized posi- 
tions increased by only 2.9 percent from 609 to 626. Since the passage of the 
Act, the obligational authority for the Institute has increased by about 23 per- 
cent. If one includes the release of approximately $43 million in impounded FY 
73 funds during FY 74, the increase in authority is about 41 percent. During 
the same period of time, there has been a modest increase in the number of autho- 
rized positions to 664. However, during this period there has been an increased 
emphasis on clinical trials, other collaborative programs, and specialized pro- 
grams such as Specialized Centers of Research, all of which require a high ratio 
of manpower to dollar expenditure for effective management and coordination. 

The NHLI Summary of May 1973 projected staff needs of 764 in FY 74, up from a 
base of 626 positions in FY 73, and a further increase to approximately 810 
positions in FY 76. Our current position ceiling is 664 for FY 74 and the same 
number for FY 75. These position allocations are substantially below our esti- 
mates of staffing needs for the program outlined in this report, even in view 
of the above-mentioned efforts to conserve manpower. 



150 



APPENDIX A 
NATIONAL HEART, BLOOD VESSEL, LUNG, AND BLOOD ACT OF 1972 




APPENDIX A 
NATIONAL HEART, BLOOD VESSEL, LUNG, AND BLOOD ACT OF 1972 



Public Law 92-423 

92nd Congress, S. 3323 

September 19, 1972 

9n2ct 

To amend the Public Health Service Act to enlarge the authority of the .National 
Heart and Lung Institute In order to advance the national attack against 
diseases .if the heart and Wood vessels, the lungs, ami Miaul, and for other 
purposes. 

He it enacted by the. Senate and Howe, of ffepiimnitiitim of Hie 
I 'lilted State* of A me lira in Congre** mmemb/eil. National Heart, 

Blood Vessel, 

SHORT TITLE LU "«' ^J? .f^ 

Act of 1972. 

Section 1. This Act may be cited as the "National Heart. Wood 
Vessel, Lung, and Blood Act of 1972". 

FINDINGS AND DECLARATION OF I'l RIN1KK 

Sec. 2. (a) Congress finds and declares that — 

(1) diseases of the heart and blood vessels collectively cause 
more than half of all the deaths each year in the United States 
and the combined effect of the disabilities and deaths from such 
diseases is having a major social and economic impart on the 
Nation; 

(2) elimination of heart and blood vessel diseases as significant 
causes of disability and death could increase the average Ameri- 
can's life expectancy by about eleven years and could provide for 
annual savings to the economy in lost wages, productivity, and 
costs of medical care of more than $30,000,000,000 per year ; 

(3) chronic lung diseases have been gaining steadily in recent 
years as important causes of disability and death, with emphysema 
alone being the fastest rising cause of death in the United States; 

(4) chronic respiratory diseases affect an estimated ten million 
Americans, emphysema an estimated one million, chronic bron- 
chitis an estimated four million, and asthma an estimated five 
million ; 

(5) thrombosis (the formation of blood clots in the vessels) 
may cause, directly or in combination with other problems, many 
deaths and disabilities from heart disease and stroke which can 
now be prevented; . B6 g"Tj 679 

,_. . , r . .—i— i « i ■ ■ ■ — : — ; — ? ofi <;t*t can 



(6) blood and blood products are essential human resources 66 b ™ T - t>B0 
whose value in saving life and promoting health cannot be 

assessed in terms of dollars ; 

(7) the provision of prompt and effective emergency medical 
services utilizing to the fullest extent possible advances in trans- 
portation and communications and other electronic systems and 
specially trained professional and paraprofessional health care 
personnel can reduce substantially the number of fatalities and 
severe disabilities due to critical illnesses in connection with heart, 
blood vessel, lung, and blood diseases; and 

(8) the greatest potential for advancement against heart, blood 
vessel, lung, and blood diseases lies in the National Heart and 
Lung Institute, but advancement against such diseases depends 
not only on the research programs of that Institute but also on 
the research programs of other research institutes of the National 
Institutes of Health. 

|b) It is the purpose of this Act to enlarge the authority of the 
National Heart and Lung Institute in order to advance the. national 
attack upon heart, blood vessel, lung, nnd blood diseases. 



63-749 O (260) 



A-l 



Pub. Law 92-423 - 2 - September 19, 1972 

HEART, BLOOD VESSEL, I.UNU, AND BLOOD DISEASE PROI1RAMB 

62 stnt. 464. Sec. 8. Part B of title IV of the Public Health Service Act is 

42 use 267- amended (1) by redesignating section 413 as section 419A. (2) by 

287o « redesignating section 414 as section 418, and (3) by adding after sec- 

tion 412 the following new sections: 

"NATIONAL HEART, BLOOD VESSEL, L0NO, AND BLOOD DISEASE PROGRAM 

"Sec. 413. (a) The Director of the Institute, with the advice of the 

Council, shall develop a plan for a National Heart, Blood Vessel, 

Lung, and Blood Disease Program (hereafter in this part referred 

to as the 'Program') to expand, intensify, and coordinate the activities 

of the Institute respecting heart, blood vessel, lung, and blood diseases 

(including its activities under section 412) and shall carry out the 

nih, coordln- Program in accordance with such plan. The Program shall be coordi- 

ation pro- nated with the other research institutes of the National Institutes of 

visions. Health to the extent that they have responsibilities respecting such 

diseases and shall provide for — 

"(1) investigation into the epidemiology, etiology, and preven- 
tion of all forms and aspects of heart, blood vessel, lung, and blood 
diseases, including investigations into the social, environmental, 
behavioral, nutritional, biological, and genetic determinants and 
influences involved in the epidemiology, etiology, and prevention 
of such diseases; 

"(2) studies and research into the basic biological processes and 
mechanisms involved in the underlying normal and abnormal 
heart, blood vessel, lung, and blood phenomena ; 

"(3) research into the development, trial, and evaluation of 
techniques, drugs, and devices (including computers) used in, 
and approaches to, the diagnosis, treatment (including emergency 
medical service), and prevention of heart, blood vessel, lung, and 
blood diseases and the rehabilitation of patients suffering from 

86 stat. 660 such d iseases ; 

86 stat. 681 "(4) establishment of programs that will focus and apply sci- 

entific and technological efforts involving biological, physical, and 
engineering sciences to all facets of heart, blood vessel, lung, and 
blood diseases with emphasis on refinement, development, and 
evaluation of technological devices that will assist, replace, or 
monitor vital organs and improve instrumentation for detection, 
diagnosis, and treatment of those diseases ; 

"(5) establishment of programs for the conduct and direction 
of field studies, large-scale testing and evaluation, and demon- 
stration of preventive, diagnostic, therapeutic, and rehabilitative 
approaches to, and emergency medical services for, such diseases ; 
"(6) studies and research into blood diseases and blood, and 
into the use of blood for clinical purposes and all aspects of the 
management of its resources in this country, including the collec- 
tion, preservation, f ractionalization, and distribution of it and its 
products ; 

"(7) the education and training of scientists, clinicians, and 
educators, in fields and specialties (including computer sciences) 
requisite to the conduct of programs respecting heart, blood ves- 
sel, lung, and blood diseases ; 

"(8) public and professional education relating to all aspects 
of such diseases and the use of blood and blood products and the 
management of blood resources : 

"(9) establishment of programs for study and research into 
heart, blood vessel, lung, and blood diseases of children (including 
cystic fibrosis, hyaline membrane, and hemolytic ami hemophilic 



A- 2 



September 19, 1972 - 3 - Pub. Law 92-423 

diseases) and for the development and demonstration of diagnos- 
tic, treatment, and preventive approaches to these diseases; and 
"(10) establishment of programs for study, research, develop- 
ment, demonstrations and evaluation of emergency medical serv- 
ices for people who become critically ill in connection with heart, 
blood vessel, lung, or blood diseases, which programs shell 
include programs for (A) the training of paraprofessionals in 
( i) emergency treatment procedures, and ( ii ) utilization and oper- 
ation of emergency medical equipment, (B) the development and 
operation of (i) mobile critical care units (including helicopters 
and other airborne units where appropriate), (ii) radio, tele- 
communications, and other means of communications, and (iii) 
electronic monitoring systems, and (C) the coordination with 
other community services and agencies in the joint use of all forms 
of emergency vehicles, communications systems, and other appro- 
priate services. 
The Program shall give special emphasis to the continued develop- National insti- 
ment in the Institute of programs relating to atherosclerosis, hyper- tute of Neuroiog- 
tension, thrombosis, and congenital abnormalities of the blood vessels lcal Diseases 
as causes of stroke, and to effective coordination of such programs "") stroke, co- 
with related stroke programs in the National Institute of Neurological 
Diseases and Stroke. 

"(b) (1) The plan required by subsection (a) of this section shall Plan development; 
(A) be developed within one hundred and eighty days after the effec- transmittal to 
tive date of this section, (B) be transmitted to the Congress, and (C) c°n8™ss. 
set out the Institute's staff requirements to carry out the Program and 86 stat. 681 
recommendations for appropriations for the Progr am. > ^86 stat. 682 

"(2) The Director or the Institute shall, as soon as practicable after Report to Pres- 
the end of each calendar year, prepare in consultation with the Coun- ident, trans- 
cil and submit to the President for transmittal to the Congress a nittal to Con- 
report on the activities, progress, and accomplishments under the e resa - 
Program during the preceding calendar year and a plan for the Pro- 
gram during the next five years. 

"(c) In carrying out the Program, the Director of the Institute, Director, funo- 
under policies established by the Director of the National Institutes tions. 
of Health and after consultation with the Council and without regard 
to any other provision of this Act, may — 

"(1) if authorized by the Council, obtain (in accordance with 
section 3109 of title 5, United States Code, but without regard to so stat. 416. 
the limitation in such section on the number of days or the period 
of such service) the services of not more than fifty experts or con- 
sultants who have scientific or professional qualifications ; 

"(2) acquire, construct, improve, repair, operate, and maintain 
heart, blood vessel, lung, and blood disease laboratory, research, 
training, and other necessary facilities and equipment, and related 
accommodations as may be necessary, and such other real or per- 
sonal property (including patents) as the Director deems neces- 
sary; and acquire, without regard to the Act of March 3, 1877 
(40 U.S.C. 34), by lease or otherwise, through the Administrator 19 stat. 370. 
of General Services, buildings or parts of buildings in the District 
of Columbia or communities located adjacent to the District of 
Columbia for the use of the Institute for a period not to exceed 
ten years; and 

"(3) enter into Buch contracts, leases, cooperative agreements, 
or other transactions, without regard to sections 3648 and 3709 of 
the Revised Statutes of the United States ( 31 U.S.C. 529, 41 U.S.C. 
5), as may be necessary in the conduct of his functions, with any 
public agency, or with any person, firm, association, corporation, 
or educational institution. 



A-3 



Pub. Law 92-423 



- 4 



September 19, 1972 



Assistant Dtrec 
tor for Health 
Information Pro- 
grams. 

Cardiovascular 
and pulmonary 
diseases, in- 
formation. 



B6 STAT. 6B2 
86 STAT. 663 

Appropriations . 



"(d) There shall be in the Institute an Assistant 1 h' rector for Health 
Information Programs who shal! be appointed by the Director of the 
Institute. The Director of the Institute, acting through the Assistant 
Director for Health Information Programs, shall conduct a program 
to provide the public and the health professions with health informa- 
tion with regard to cardiovascular and pulmonary diseases. In the 
conduct of such program, special emphasis shall be placed upon dis- 
semination of information regarding diet, exercise, stress, hyperten- 
sion, cigarette smoking, weight control, and other factors affecting the 
prevention of arteriosclerosis and other cardiovascular diseases ami of 
pulmonary diseases. 

"heart, blood vessel, lung, and blood disease prevention and 
control programs 

"'Sec. 414. (a) The Director of the Institute, under policies estab- 
lished by the Director of the National Institutes of Health and after 
consultation with the Council, shall establish programs as necessary 
for cooperation with other Federal Health agencies, State, local, and 
regional public health agencies, and nonprofit private health agencies 
in the diagnosis, prevention, and treatment (including the provision 
of emergency medical services) of heart, blood vessel, lung, and blood 
Tiseases, appropriately emphasizing the prevention, diagnosis, and 
treatment of such diseases of children. 

''(b) There is authorized to be appropriated to carry out this 
section $25,000,000 for the fiscal year ending June 30, 1973, $35,000,000 
for the fiscal year ending June 30, 1974, and $45,000,000 for the fiscal 
ypar ending June 30. 1975. 

"NATIONAL RESEARCH AND DEMONSTRATION CENTERS FOR HEART, BI.OOD 
VESSEL, LUNG, AND BLOOD DISEASES 

"Sec. 415. (a) (1) The Director of the Institute may provide for the 
development of — 

"(A) fifteen new centers for basic and clinical research into, 
training in, and demonstration of, advanced diagnostic, preven- 
tion, and treatment methods (including methods of providing 
emergency medical services) for heart, blood vessel, and blood 

Q1SG&SCS " &rid 

"(B) fifteen new centers for basic and clinical research into, 
training in, and demonstration of, advanced diagnostic, preven- 
tion, and treatment methods (including methods of providing 
emergency medical services) for chronic lung diseases (including 
bronchitis, emphysema, asthma, cystic fibrosis, and other lung 
diseases of children). .,,>,., in- 

"(2) The centers developed under paragraph (1)(A) shall, in 
addition to being utilized for research, training, and demonstrations, 
I* utilized for the following prevention programs for cardiovascular 

(iidcftscs * 

"(A) Programs to develop improved methods of detecting 
individuals with a high risk of developing cardiovascular disease. 

"(B) Programs to develop improved methods of intervention 
against those factors which cause individuals to have a high risk 
of developing such disease. 

"(C) Programs to develop health professions and allied health 
professions personnel highly skilled in the prevention of such 

"(D) Programs to develop improved methods of providing 
emergency medical services for persons with such disease. 



A-4 



September 19, 1972 - 5 - Pub. Law 92-423 

"(3) Centers developed under this subsection may be supported 
under subsection (b) or under any other applicable provision of law. 
The research, training, and demonstration activities carried out 
through any such center may relate to any one or more of the diseases 
referred to in paragraph ( 1 ) of this subsection. 

"(b) The Director of the Institute, under policies established by the Public or non- 
Director of the National Institutes of Health and after consultation profit agencies, 
with the Council, may enter into cooperative agreements with public or cooperative 
nonprofit private agencies or institutions to pay all or part of the cost a « re ™ en ' ts - 
of planning, establishing, or strengthening, and providing basic oper- 
ating support for, existing or new centers (including centers estab- 
lished under subsection (a) ) for basic or clinical research into, training 
in. and demonstration of, advanced diagnostic, prevention, and treat- 
ment methods for heart, blood vessel, lung, or blood diseases. Funds Use of funds. 
paid to centers under cooperative agreements under this subsection 
may be used for — 

"(1) construction, notwithstanding section 405, 58 stat. 708. 

"(2) staffing and other basic operating costs, including such 42 usc 265 - 

patient care costs as are required for resear ch, 86 stat. 683 

"(3) training, including training for allied health professions B6 STAT - 684 
personnel, and 
"(4) demonstration purposes. 
The aggregate of payments (other than payments for construction) Limitations. 
made to any center under such an agreement may not exceed $5,000,000 
in any year. Support of a center under this subsection may be for a 
period of not to exceed five years and may be extended bv the Director 
of the Institute for additional periods of not more than five years each, 
after review of the operations of such center by an appropriate scien- 
tific review group established by the Director. As used in this section, "Construction." 
the term 'construction' does not include the acquisition of land. 

"interagency technical committee 

"Sec. 416. (a) The Secretary shall establish an Interagency Tech- Establishment, 
nical Committee on Heart, Blood Vessel, Lung and Blood Diseases 
and Blood Resources which shall be responsible for coordinating those 
aspects of all Federal health programs and activities relating to heart, 
blood vessel, lung, and blood diseases and to blood resources to assure 
the adequacy ana technical soundness of such programs and activities 
and to provide for the full communication and exchange of informa- 
tion necessary to maintain adequate coordination of such programs and 
activities. 

"(b) The Director of the Institute shall serve as Chairman of the 
Committee and the Committee shall include representation from all 
Federal departments and agencies whose programs involve health 
functions or responsibilities as determined by the Secretary. 

"national heart and lino advisory council 

"Sec. 417. (a) There is established in the Institute a National Heart Establishment; 
and Lung Advisory Council to be composed of twenty-three members membership, 
as follows : 

"(1) The Secretary, the Director of the National Institutes of 

Health, the Director of the Office of Science and Technology, and 

the chief medical officer of the Veterans' Administration (or their 

designees), and a medical officer designated by the Secretary of 

Defense, shall be ex officio members of the Council. 

"(2) Eighteen members appointed by the Secretary. 

Eleven of the appointed members shall be selected from among the 

leading medical or scientific authorities who are skilled in the sciences 



A- 5 



Pub. Law 92-423 



- 6 



September 19, 1972 



Terms. 



66 STAT. 684 



relating to diseases of the heart, blood vessels, lungs, and blood; two 
of the appointed members shall be selected from persons enrolled in 
residency programs providing training in heart, blood vessel, lung, or 
blood diseases; and five of the appointed members shall be selected 
from members of the genera] public who are leaders in the fields of 
fundamental or medical sciences or in public affairs. 

"(b) (1) Each appointed member of the Council shall be appointed 
for a term of four years, except that — 

"(A) any member appointed to fill a vacancy occurring prior 
to the expiration of the term for which his predecessor was 



86 STAT. 685 



National Ad- 
visory Heart 
Council, re- 
placement pro- 
visions. 
64 Stat. 446. 
42 USC 218. 



5 USC 5332 
note. 



80 Stat. 499 j 
83 Stat. 190. 



Executive Sec- 
retary. 



appointed shall be appointed for the remainder of such term ; and 

(B) of the members first appointed after the effective date of 

this section, five shall be appointed for a term of four years, five 

shall be appointed for a term of three years, five shall be appointed 

for a term of two years, and three shall be appointed for a term 

of one year, as designated by the Secretary at the time of 

appointment. 

Appointed members may serve after the expiration of their terms until 

their successors have taken office. 

"(2) A vacancy in the Council shall not affect its activities, and 
twelve members of the Council shall constitute a quorum. 

"(3) The Council shall supersede the existing National Advisory 
Heart Council appointed under section 217, and the appointed mem- 
bers of the National Advisory Heart Council serving on the effective 
date of this section shall serve as additional members of the National 
Heart and Lung Advisory Council for the duration of their terms 
then existing, or for such shorter time as the Secretary may prescribe. 

" (4) Members of the Council who are not officers or employees of 
the United States shall receive for each day they are engaged in the 
performance of the functions of the Council compensation at rates 
not to exceed the daily equivalent of the annual rate in effect for grade 
GS-18 of the General Schedule, including traveltime ; and all mem- 
bers, while so serving away from their homes or regular places of 
business, may be allowed travel expenses, including per diem in lieu 
of subsistence, in the same manner as such expenses are authorized by 
section 5703 of title 5, United States Code, for persons in the Govern- 
ment service employed intermittently. 

"(c) The Secretary (or his designee) shall be the Chairman of the 
Council. 

"(d) The Director of the Institute shall (1) designate a member of 
the staff of the Institute to act as Executive Secretary of the Council, 
and (2) make available to the Council such staff, information, and 
other assistance as it may require to carry out its functions. 

" (e) The Council shall meet at the call of the Chairman, but not less 
often than four times a year." 



Ante, p. 680. 



AUTHORIZATION OF APPROPRIATIONS FOR PART B Or TITLE IV OF THE PUBLIC 
IIF-ALTIt 8ERVICF. ACT 

Sec. 4. Part B of title IV of the Public Health Service Act is 
amended by adding at the end thereof the following new section : 



AUTHORIZATION OF APPROPRIATIONS 

"Sec. 419B. For the purpose of carrying out this part (other than 
Ante , p. 682. section 414), there is authorized to be appropriated $375,000,000 for 
the fiscal year ending June 30, 1973, $425,000,000 for the fiscal year 
ending June 30, 1974, and $475,000,000 for the fiscal year ending 
June 30, 1975. Of the sums appropriated under this section for any 
fiscal year, not less than 15 per centum of such sums shall be reserved 



A-6 



September 19. 1972 - 7 - Pub. Law 92-423 g6 „„_ M6 

for programs under this part respecting diseases of the lung and not 
less than 15 per centum of such sums shall lie reserved for programs 
under this part for programs respecting diseases of the blood." 

At TIIOR1TY OF THE DIRECTOR OF THE NATIONAL HEART AND l.l'XU 
INST1TI TE TO APPROVE GRANTS 

Sec. .">. Section 41!)A of the Public Health Service Act (as so 
redesignated hy section 3 of this Act ) is amended — 

(1) by striking out "grants-in-aid" in subsection (a) anil 
inserting in lieu thereof "except as provided in subsection (<•), 
grants-in-aid": and 

(2) by adding after subsection (b) the following new 
subsection : 

"(c) Older procedures approved by the Director of the National 
Institutes of Health, the Director of the. National Heart and Lung 
Institute may approve grants under this Act for research and training 
ill heart, blood vessel, lung, and blood diseases — 

"(1 ) in amounts not to exceed $35,000 after appropriate review Limitations. 
for scientific merit but without review and recommendation by 
the Council, and 

"(2) in amounts exceeding $35,000 after appropriate review 
for scientific meril and recommendation for approval bv the 
Council/' 

CONFORMING AMENDMENTS TO PART 11 OF TITLE IV OF THE Pl'BI.K' HEALTH 
SERVICE ACT 

Sec. *>. (a) Section 411 of the Public Health Service Act is amended 62 Stat. 465. 
by striking out "National Heart Institute" anil inserting in lieu 4 j usc 2ii. 
thereof "National Heart and Lung Institute". 

(b) Section 412 of such Act is amended — *2 usc 287a. 

(1) by striking out "heart" each place it occurs (except in the 
heading) and inserting in lieu thereof "heart, blood vessel, lung, 
and blood"; 

(2) by striking out "Surgeon General" and inserting in lieu 
thereof "'Secretary" : 

(3) by striking out "National Advisory Heart Council" and 
inserting in lieu thereof "National Heart and Lung Advisory 
Council"; 

(4) by redesignating paragraphs (a), (b), (c), (d), (e), (f), 
and (g) as paragraphs (1). (2), (3), (4). (5), (6), and (7), 
respectively : and 

(5) by amending the section heading to read as follows: 

•'RESEARCH AND TRAINING IN DISEASES OF THE HEART, BLOOD VESSELS, 
LFXG. AND BLOOD" 

(c) Section 418 of such Act (as so redesignated by section 3 of this 
Act) is amended — 

(1) by inserting "(a)" immediately after "Sec 418." and by- 
adding at the end thereof the following new subsection : 

"(b)(1) The Council shall advise and assist the Director of the 
Institute with respect to the Program established under section 413. Ante, p. 680. 
The Council may hold such hearings, take such testimony, and sit and 
art at such times and places, as the Council deems advisable to inves- 
tigate programs and activities of the Program. 

"(2) The Council shall submit a report to the President for trans- Report to Pres- 
mittal to the Congress not later than January 31 of each year on the ident, trans- 
progress of the Program toward the accoinplishment of its objectives." ™l ttal to c ° n - 



A-7 



Pub. Law 92-423 - 8 - September 19, 1972 



86 STAT. 687 



(2) by striking out "Surgeon General" each place it occurs 
(except paragraph (f ) ) and inserting in lieu thereof "Secretary"; 

(3) by striking out "heart" each place it occurs and inserting 
in lieu thereof "heart, blood vessel, lung, and blood"; 

(4) by striking out "Surgeon General" in paragraph (f ) and 
inserting in lieu thereof "Secretary, the Director of the National 
Institutes of Health, and the Director of the. National Heart and 
Lung Institute" ; and 

(5) by redesignating paragraphs (a), (b), (c), (d), (e), and 
(f) as paragraphs (1), (2), (3), (4), (5), and (6), respectively. 

(d) Section 419A of such Act (as so redesignated by section 3 of 
this Act) is amended — 

(1) in subsection (a), by (A) striking out "Surgeon General" 
and inserting in lieu thereof "Secretary", and (B) striking out 
"heart" and inserting in lieu thereof "heart, blood vessel, lung, 
and blood" ; and 

(2) in subsection (b), by (A) striking out "The Surgeon Gen- 
eral shall recommend to the Secretary acceptance of conditional 

58 stat. 709. gifts, pursuant to section 501," and inserting in lieu thereof "The 

42 use 219. Secretary may, in accordance with section 501, accept conditional 

gifts", and (B) striking out "heart" and inserting in lieu thereof 

"heart, blood vessel, lung, and blood". 

(e) The heading for part K of such Act is amended to lead as 
follows : 

"Part B — National Heart and Lung Institute". 

CONFORMINC. AMENDMENTS TO OTHER PROVISIONS OF THE PUBLIC 
HEALTH SERVICE ACT 

64 stat. 446. ^ EC - ?■ ( a ) Section 217 of such Act is amended — 

42 use 218. ' <1) by striking out "the National Advisory Heart Council," 

each place it occurs in subsection (a) ; 

(2) by striking out "heart diseases," in subsection (a) and by 

striking out "heart," in subsection (b). 
58 stat. 692; (b) Sections 301(d) and 301(i) of such Act are each amended by 

62 Stat! 601j striking out "National Advisory Heart Council" and inserting in lieu 
79 stat. 448. thereof "National Heart and Lung Advisory Council". 
42 USC 241. 

REPORT TO CONGRESS 

Review. Sec. 8 - The Secretary of Health, Education, and Welfare shall carry 

out a review of all administrative processes under which the National 
Heart, Blood Vessel, Lung, and Blood Disease Program, established 

Ante , p. 680. under part B of title IV of the Public Health Service Act, will operate, 
including the processes of advisory council and peer group reviews, in 
order to assure the most expeditious accomplishment of the objectives 
of the Program. Within one year of the date of enactment of this Act, 
the Secretary shall submit a report to the Congress of the findings of 
such review and the actions taken to facilitate the conduct of the Pro- 
gram, together with recommendations for any needed legislative 
changes. 



A- 8 



September 19, 1972 - 9 - Pub. Law 92-423 

86 STAT, 



EFFECTIVE DATE 



Sec. 9. This Act and the amendments made by this Act shall take 
effect sixty days after the date of enactment of this Act or on such Publication in 
prior date after the date of enactment of this Act as the President Federal Register. 
shall prescribe and publish in the Federal Register. 

Approved September 19, 1972. 



LEGISLATIVE HISTORY : 

HOUSE REPORTS: No. 92-1108 aooompanying H.R. 15081 (Comm. on 

Interstate and Foreign Commerce) and No. 92-1349 
(Comm. of Conference). 
SENATE REPORTS: No. 92-733 (Comm. on Labor and Publio Welfare) e 

No. 92-1068 (Comm. of Conference). 
CONGRESSIONAL RECORD, Vol. 118 (1972): 

Apr, 7, considered and passed Senate. 

July 18, considered and passed House, amended, in lieu 

of H.R. 15081. 
Aug. 18, House agreed to oonferenoe report, 
Sept. 6, Senate agreed to oonferenoe report. 
WEEKLY COMPILATION OF PRESIDENTIAL DOCUMENTS, Vol. 6, No. 39: 
Sept, 20, Presidential statement. 



A-9 



APPENDIX B 
DEFINITION OF MAJOR PROBLEM AREAS 



APPENDIX B 

DEFINITION OF MAJOR PROBLEM AREAS 



The major problem areas addressed by the National Heart, Blood Vessel, Lung, 
and Blood Act of 1972 are heart and blood vessel diseases, lung diseases, and 
blood diseases and blood resources. This appendix includes for each major prob- 
lem area definitions of the disease problems covered by the program, discussion 
of the relationship of the disease problem to other diseases and/or disorders, 
and statistical data on the impact and scope of the disease problem in the United 
States. This appendix is reprinted directly from Section II, Volume I, the 
National Heart and Lung Institute Summary (May 1, 1973) of the National Heart, 
Blood Vessel, Lung, and Blood Program. Two additional lung disease problems, 
which have been designated major problem areas in the updated 5-year Plan, have 
been added at the end. Circulatory Assistance, Respiratory Assistance, and 
Biomaterials are not disease problem areas. However, they constitute three of 
the 22 major program elements and play important roles in the treatment of sev- 
eral of the major diseases in the National Program. A brief definition of each 
has also been added to this appendix. 



B-l 



DEFINITION OF MAJOR PROBLEM AREAS 



The four major problem areas covered by the National 
Heart, Blood Vessel, Lung and Blood Act are discussed 
separately in the following three sections: Heart and 
Blood Vessel Diseases, Lung Diseases, Blood Diseases 
and Blood Resources. As pointed out in the Report of 
the Panel Chairmen, there are many interrelationships 
among these problem areas. The Chairmen state: 
"Disordered biological functions seldom involve a 
single area. As examples, pulmonary embolism begins 
with thrombosis and involves the lung and its circula- 
tion as well as the heart. Effective delivery of oxygen 
to the tissue depends on the lung, the heart, the 
amount, type, and functional states of the hemoglobin, 
and the peripheral circulation." 

HEART AND BLOOD 
VESSEL DISEASES 

For more than fifty years, heart and blood vessel dis- 
eases have been the major cause of death in this 
country. They now account for 54 percent of all 
deaths annually (Figure 2). This is more than three 
times the death rate from cancer, the next highest 
cause. An estimated 28 million Americans have diseases 
of the heart and blood vessels, resulting in a large bur- 
den of acute and chronic illness and disability. Hence, 
there is reason for referring to heart and blood vessel 
diseases as the modern epidemic. Moreover, heart and 
blood vessel diseases cost the economy more than $30 
billion per year in wages, lost productivity, and ex- 
penses for medical care. 



Figure 2 
DEATHS FROM ALL CAUSES 
UNITED STATES. 1967 




Nine major problem areas in heart and blood vessel 
diseases are defined below: Arteriosclerosis, Hyperten- 
sion, Cerebrovascular Disease, Coronary Heart Disease, 
Peripheral Vascular Diseases, Arrhythmias, Heart Fail- 
ure and Shock, Congenital and Rheumatic Heart Dis- 
eases, and Cardiomyopathy and Infections of the 



B-2 



Heart. Of these, arteriosclerosis and hypertension are 
considered the major cardiovascular disease problems 
in the United States. The causes of arteriosclerosis and 
most cases of hypertension are unknown. 

Arteriosclerosis, or "hardening of the arteries," is 
responsible for 84 percent of the deaths from heart and 
blood vessel diseases. It is a chronic pathological 
change in the blood vessels and its most common form 
is atherosclerosis in which the inner lining of the 
arteries becomes rough, thick, hard and covered with 
plaques. Eventually, the inner diameter of the vessels 
decreases and blood flow in the diseased arteries di- 
minishes or stops completely. Atherosclerosis begins 
early in life and is asymptomatic for years. Virtually all 
adult American males, and postmenopausal women, 
are afflicted to some degree. The disease manifests it- 
self in many ways, but primarily as heart attacks, 
strokes and occlusive disease of the peripheral vessels. 
Therefore, if arteriosclerosis could be prevented, 
hundreds of thousands of lives might be prolonged. 
International statistics reveal a great variation in death 
rates for coronary heart disease. For instance, in 
Denmark, Norway, and Sweden, the death rate for men 
under the age of 55 is less than half that for the same 
age group in the United States. This difference 
indicates that the high death rates due to 
arteriosclerosis in the United States are neither 
necessary nor inevitable. 

Hypertension, or high blood pressure, is one of the 
most commonly encountered forms of heart and blood 
vessel diseases, affecting an estimated 23 million adult 
Americans, or between 10 and 15 percent of the popu- 
lation. High blood pressure is the most important 
factor contributing to the development of strokes. It 
also accelerates the development of atherosclerosis in 
the coronary and peripheral vessels. Control of hyper- 
tension would, therefore, reduce the incidence of three 
major causes of death and disability: stroke, coronary 
heart disease and peripheral vascular disease. High 
blood pressure is easy to detect, but may exist for 
many years without symptoms. It can be controlled 
with presently available therapy. However, of the 
millions of Americans with this disease, one half are 
probably unaware that they have it, and of those who 
are aware, less than one half are receiving adequate 
therapy. Although hypertension is widely distributed 
among Americans, it has been found to be more 
common and severe among the black population. 

Cerebrovascular Disease occurs when an artery 
supplying blood to the brain is blocked, ruptured, or 
injured. Cerebrovascular disease due to arteriosclerosis 
and especially due to hypertension is the basis for the 



great majority of strokes. The individual and public 
health burden of death, paralysis and brain damage is 
large. Of the 1.7 million adults who have this disease, 
700,000 are partially or completely disabled. Stroke 
kills about 200,000 persons a year, more men than 
women, and at a greater rate among blacks than whites. 
Each year, some 530,000 patients are discharged from 
our hospitals with a diagnosis of stroke, and each year 
about 250,000 individuals, between the ages of 25 and 
64, are crippled mentally or physically by a stroke. 
Many more lives could be saved and disabilities pre- 
vented if we had effective methods for prevention and 
treatment of arteriosclerosis and hypertension and if 
available treatment were more widely applied. It 
should be noted that, due to the recent advances in 
therapy for high blood pressure, there has been an 
appreciable long-term decrease in deaths from stroke. 

Coronary Heart Disease refers to atherosclerosis in the 
arteries that supply the heart muscle. A heart attack is 
a manifestation of coronary heart disease and occurs 
when a coronary artery is blocked, preventing the 
blood from reaching the heart muscle. This produces 
death of the heart muscle, technically called myo- 
cardial infarction. Coronary heart disease is the major 
manifestation of atherosclerosis. It is the predominant 
form of heart disease in the adult American and causes 
1.25 million heart attacks a year, and is responsible for 
chronic illness in 4 million Americans, 2.5 million be- 
low the age of 65. In 1969, coronary heart disease 
accounted for about 675,000 deaths in this country. It 
is the largest single cause of death from cardiovascular 
disease and is the leading cause of death in both men 
and women. Each year, approximately 130,000 per- 
sons in their most productive years (below age 65) die 
of coronary heart disease. 

Coronary heart disease may also result in angina pec- 
toris (a pain usually located in the chest and arm that is 
brought on by exercise, exposure to cold, and other 
factors), heart failure (impaired pumping performance 
of the heart leading to accumulation of fluid in the 
body and congestion in the lungs), disturbances of 
heart rhythm and sudden death. Each year, 400,000 
deaths from coronary heart disease occur suddenly or 
before hospitalization. Half of these occur 
instantaneously and unwitnessed. Either heart disease 
or hypertension is evident in 300,000 of these cases, 
but in 100,000, sudden cardiac death is the first 
evidence of heart disease. 

Peripheral Vascular Diseases are abnormalities that 
occur within arteries or veins. Atherosclerotic narrow- 
ing may result in inadequate blood flow through the 



B-3 



arteries. The veins may become dilated (varicosities) or 
inflamed and obstructed by blood clots (thrombo- 
phlebitis). These diseases may be painful and result in 
organ damage, skin ulcerations and gangrene. 
Peripheral vascular diseases are a significant cause of 
disability and illness. For example, peripheral vascular 
disease in the legs may affect one's ability to walk or 
run. Thrombosis in the veins may produce pulmonary 
embolism; i.e., clot fragments may be carried in the 
blood from their site of origin to the lungs. This in turn 
may result in shock and death. Leg vein thrombosis is 
the cause of more than 90 percent of pulmonary 
emboli which in turn are responsible for approximately 
50,000 deaths a year in this country. About 265,000 
patients are discharged from our hospitals each year 
with a primary diagnosis of peripheral vascular disease. 

Arrhythmias, or abnormal heart rhythms, occur with 
many forms of heart disease and result from an altera- 
tion in the normal transmission of electrical impulses 
within the heart. They may also occur without rec- 
ognizable disease. Many rhythm disturbances have 
minor influence upon life expectancy and cause little 
disability, others cause serious symptoms, and some are 
almost instantaneously fatal. For example, arrhythmias 
kill more than half of the patients with coronary heart 
disease and are a major problem in patients with rheu- 
matic heart disease. 

Heart Failure and Shock represent major causes of 
death and may be the end result of many different 
diseases. Heart failure occurs when the heart has been 
damaged so extensively that its ability to pump blood 
is impaired and it can no longer meet the needs of the 
body. In its chronic form, it is often associated with 
shortness of breath, accumulation of fluids and 
swelling of the legs. Shock is also a secondary 
phenomenon characterized by an inability of the heart 
and peripheral circulation to maintain adequate blood 
pressure or blood perfusion. Left untreated, it rapidly 
leads to irreversible damage to the tissues, and to 
death. Shock can be a complication of many disorders 
such as heart attacks, hemorrhage, or burns and stroke. 

Heart failure and shock are the primary causes of in- 
hospital deaths from heart attack and most other types 
of heart disease, thus accounting for over a quarter 
million deaths annually. In addition, chronic heart 
failure may follow a heart attack or result from high 
blood pressure or other heart diseases. Over two mil- 
lion Americans have chronic heart failure, and each 
year the total cost of their hospitalization exceeds 
$500 million. In the majority, symptoms can be 
relieved by drugs. 



Congenital and Rheumatic Heart Diseases are impor- 
tant diseases of children. Congenital heart disease 
occurs when the heart or major blood vessels near the 
heart fail to mature normally before birth. About eight 
out of every 1,000 children are born with this disease, 
and half of them do not survive until their first birth- 
day. The causes of congenital heart diseases are general- 
ly unknown. Less than 3 percent are known to be 
related to a particular event or disorder occurring dur- 
ing pregnancy, such as rubella infection or the use of 
certain drugs, such as thalidomide. Rheumatic fever 
and rheumatic heart disease were once considered lead- 
ing causes of childhood illnesses. They can now be pre- 
vented. Rheumatic fever is almost always preceded by 
a streptococcal infection and may lead to damage of the 
heart valves, thus causing rheumatic heart disease. 
Rheumatic fever afflicts about 100,000 school 
children. Both congenital and rheumatic heart diseases 
cause substantial impairment of health in children, 
and in adults in their most productive years. They 
annually cause over 8,000 and 15,000 deaths, respec- 
tively, in the United States. The cost of physician care 
alone for patients with rheumatic fever and rheumatic 
heart disease was about $28 million in 1969. 

Cardiomyopathy and Infections of the Heart are dis- 
eases of the heart muscle and its linings. These diseases 
cause enlargement of the heart, heart failure, irregu- 
larities of the heart rhythm, and occasionally sudden 
death. They are the result of a variety of factors. 
Known factors include toxic substances, viral 
infections, alcohol, immunological phenomena, 
nutritional deficiencies, muscular dystrophy, and a 
number of rare diseases. The condition may be acute or 
chronic and progressive. Rapidly fatal disease may be 
associated with heart failure, disturbances of rhythm 
and sudden death. Infections may affect the heart 
muscle (myocarditis), its interior wall (endocarditis), or 
its exterior surface (pericarditis). Cardiomyopathies, 
myocarditis, endocarditis, and pericarditis are 
increasing in frequency. However, quantitative 
information concerning the prevalence of these diseases 
is not available because we still lack specific diagnostic 
criteria and laboratory tests. 

LUNG DISEASES 

The National Heart, Blood Vessel, Lung and Blood Pro 
gram encompasses respiratory diseases exclusive of 
cancer of the lung, upper respiratory infections and 
pulmonary tuberculosis. 

Respiratory diseases that represent national health 
problems include chronic obstructive pulmonary dis- 



B-4 



eases (COPD), acute respiratory distress syndromes 
(RDS), and interstitial lung diseases. The economic 
cost of these diseases has been estimated at $6.3 billion 
per year. 

Lung diseases afflict both the young and the old. In the 
newborn, the most common cause of death is the 
respiratory distress syndrome which affects between 
50,000 and 100,000 babies in the United States each 
year, about half of whom die. RDS is implicated in the 
development of adult respiratory diseases as well. Inter- 
stitial lung diseases are a major cause of lung problems 
in the young adult, and may cause COPD. Of the adult 
respiratory diseases, emphysema and chronic bronchitis 
are the major causes of death. An estimated 10 million 
Americans are currently affected by these diseases, to- 
gether with asthma. Emphysema and chronic bron- 
chitis represent a particularly pressing health problem 
since the death rate and prevalence of these conditions 
have been increasing at an alarming rate over the past 
15 years. 

As a disabling disease, emphysema is second only to 
heart disease. The illness and disability caused by 
respiratory diseases are summarized in Figure 3. 

Figure 3 

ILLNESS AND DISABILITY 

FROM RESPIRATORY DISEASES 

IN THE UNITED STATES 





ANNUAL INCIDENCE 
OF ACUTE CONDITIONS 

1.700 






PRE 
CHRON 

77 5 
million 


/ALENCE OF 

C CONDITIONS 






900 

million 


396 












375 
million 


225 




217 




i 


w, 












2.5 

millnn 






Divi of RMncud Acti-Hy C.i« Pe , wnl Pwwm 

Without Limitation With Limitation 
K£Y Of Activity of Activity 

SOURCE N««>ui Ceni*. (c Kwlih Sliimci. «<«qt wmUn di v t*i 1961 1967 



Four major lung disease problems are defined below: 
Pediatric Pulmonary Diseases, Emphysema and Chronic 
Bronchitis, Fibrotic and Immunologic Lung Diseases 
and Respiratory Failure. 



Pediatric Pulmonary Diseases present health problems 
of national dimensions. Hyaline membrane disease 
(respiratory distress syndrome of the newborn), cystic 
fibrosis (an inherited disease of abnormal mucus secre- 
tion), and bronchiolitis (acute airway obstruction in 
young children) are among the most important dis- 
orders of childhood that involve the lung and the air- 
ways. About 40,000 babies are born each year with 
hyaline membrane disease. More than half of these will 
die unless given prompt treatment, presently unavail- 
able except in a few specialized facilities. 

Cystic fibrosis occurs in about one of every 2,000 live 
births and approximately 5 percent of the general 
population in the United States carries the gene for 
this disorder. Cystic fibrosis is one of the main causes 
of chronic illness in children and young adults and 
accounts for most of the deaths from pulmonary dis- 
ease in the pediatric age group. Bronchiolitis is a 
common pediatric disorder, but data are not available 
on its incidence. 

Emphysema and Chronic Bronchitis are among the 
major causes of mortality and illness from pulmonary 
diseases. Emphysema is a disease in which the thin 
walls in the alveoli (air sacs) lose their elasticity and 
tear. Chronic bronchitis refers to a persistent inflam- 
mation of the lungs characterized by recurrent 
coughing and excess mucus in the airways. These dis- 
eases may be associated with certain risk factors, such 
as cigarette smoking, and in some cases with genetic 
determinants (e.g., deficiency of alpha! -antitrypsin 
enzyme). Emphysema is a leading cause of death in this 
country and an even greater cause of disability. Data 
from 1967 indicate that chronic bronchitis and 
emphysema account for half of the total 181,000 
man-years lost due to lung diseases. The death rate for 
chronic bronchitis increased by 80 percent between 
1958 and 1967. The death rate for emphysema in- 
creased by 172 percent in the same period to a level of 
10.6 per 100,000 population. 

Fibrotic and Immunologic Lung Diseases are induced 
by many disease factors. Fibrotic responses (prolifera- 
tion of connective tissue or scar formation) and 
immunologic responses are characteristic of a variety of 
lung diseases. Among the factors that may induce these 
responses are exposure to substances such as coal dust, 
silica, and asbestos in the environment; viral and 
bacterial infections; diseases of the connective tissue 
such as rheumatoid arthritis, lupus, and scleroderma; 
radiation damage; and exposure to substances like 
molds and dust that initiate hypersensitivity reactions. 
Diseases characterized by pulmonary fibrosis and/or 



B-5 



immunologic reactions include pneumoconiosis, sar- 
coidosis, diffuse hypersensitivity pneumonitis. 
Farmer's lung and bronchial asthma. This group of lung 
diseases is a major national health problem, second in 
magnitude among lung diseases only to emphysema 
and chronic bronchitis. 

Statistical data on fibrotic lung diseases are inadequate 
because these diseases are difficult to diagnose and 
poorly reported. However, their national health impact 
is far greater than is generally appreciated. For ex- 
ample, sarcoidosis is about 12 to 15 times more 
common among blacks than among whites in this 
country, and now outranks tuberculosis as a cause of 
disability from pulmonary insufficiency in black pop- 
ulations. It is also more common in women. 

Among immunologic lung diseases, asthma is the most 
common, affecting about 8.6 million persons in this 
country (approximately 4 percent of the population). 
It is responsible for 5 percent of all chronic disabilities 
and causes an annual loss of about 7 million work-days. 
Other immunologic lung diseases are associated with 
specific occupations where exposure to organic dusts 
or molds is high; for example. Farmer's lung in the 
north central states, Bagassosis among sugar cane 
workers in the south, and hypersensitivity pneumonitis 
from organisms growing in humidifiers and air condi- 
tioners. While none of these diseases is very common in 
the general population, their importance stems from 
their high incidence in particular environments. 

Respiratory Failure is a complication of many non- 
pulmonary diseases. Acute respiratory distress syn- 
dromes have been recognized as such only recently. 
For these two reasons, data on incidence are not avail- 
able. A conservative estimate is that 150,000 adult 
cases of acute respiratory distress syndrome occur each 
year with a mortality rate of 40 percent. These figures 
do not include failure due to chronic pulmonary dis- 
ease, (see Emphysema and Chronic Bronchitis), nor do 
they adequately reflect the true incidence because so 
many cases are unreported. 

BLOOD DISEASES AND 
BLOOD RESOURCES 

Problems of the blood are intimately related to 
cardiovascular and pulmonary diseases. Blood is a vital 
part of the circulatory system since it is the vehicle by 
which oxygen, nutrients, and other body chemicals are 
carried through the blood vessels to every part of the 
body, to be exchanged for carbon dioxide, waste 



products and chemicals which, in turn, need to be 
transported away from the tissues to other body 
organs, either for excretion from the body or for use in 
the life processes. 

Three groups of blood problems are defined below: 
Bleeding and Clotting Disorders, Sickle Cell Disease 
and Related Disorders of the Red Blood Cell, and 
Blood Resources. 

Bleeding and Clotting Disorders are closely interrelated. 
Both represent failures in maintaining the blood in an 
optimal state within the blood vessels. On one hand, 
failure means bleeding (hemorrhage) into surrounding 
tissues or outside the body. On the other hand, failure 
means inappropriate clotting (thrombosis) of the blood 
within the vessels. Clotting in the arteries deprives a 
part of the body of its blood supply; clotting in the 
veins impedes the return of blood to the heart. When 
excessive clotting affects small blood vessels and 
capillaries (collectively termed the microcirculation), 
tissues and cells cannot function well because they are 
deprived of essential oxygen, energy, regulating hor- 
mones and building blocks, and noxious waste 
products cannot be removed effectively. 

The particular portion of the body's defense mech- 
anisms responsible for maintaining the blood in an 
optimal fluid state is termed the hemostatic system. 
Excessive bleeding can result from an abnormality or 
deficiency, acquired or inherited, of any of the 
elements in the hemostatic system. Bleeding into 
organs and tissues may impair or destroy their function 
and uncontrolled, external blood loss may result in 
death. 

The consequences of abnormal clotting depend on the 
organ or region of the body in which it occurs. In 
vessels of the heart, brain, lung or other vital organs, 
the result can be catastrophic; in less vital areas, the 
effects may be mild and transitory. With time, the 
clot-dissolving mechanism restores the integrity of the 
circulation. However, the speed of this process is 
insufficient in the case of vital organs where even a 
very brief deprivation of blood supply results in 
irretrievable loss of function or death of tissue 

The impact of the clotting and bleeding disorders is 
considerable. Arterial thrombosis causes or complicates 
a great variety of diseases in all parts of the body; for 



B-6 



example, thrombosis involving the vessels of the kidney 
contributes to kidney failure, and arterial thrombosis 
and cerebral hemorrhage play major roles in stroke. 

Thrombosis in the veins may produce pulmonary 
embolism; that is, clot fragments may be carried in the 
blood from their site of origin to the lungs. About 
300,000 persons are hospitalized annually and more 
than 50,000 die with pulmonary embolism. Clotting in 
the venous circulation complicates many illnesses and 
surgical procedures. Autopsy studies show evidence of 
venous thrombosis in about 50 percent of cases 
examined, regardless of cause of death. 

The microcirculation is a very important component of 
the circulation system. It conveys to the cells of the 
body the substances needed for their metabolism and 
regulation, and carries away their products so that the 
internal environment is maintained in a manner which 
allows the cells to survive and perform their inter- 
related tasks. Bleeding and clotting in the micro- 
circulation are contributory or primary mechanisms in 
hypertension, stroke, diabetes, infectious and inflam- 
matory disease, autoimmune disease, host-graft rejec- 
tion, cancer, sickle cell anemia, drug toxicity, mis- 
matched blood transfusion, liver disease, and nephritis. 
The impact is vast even if it cannot be expressed 
statistically. 

Thrombosis induced by contact of the blood with 
foreign surfaces remains the major unsolved problem in 
the development of artificial organs, prosthetic vessels 
or devices that temporarily assist the circulation. 

Excessive blood loss due to inadequate or disturbed 
function of a component of the hemostatic mechanism 
is a major cause of death and morbidity in a variety of 
circumstances such as after severe injury, after surgery, 
in leukemia, and in cirrhosis of the liver. The threat of 
hemorrhage limits the aggressive management of some 
forms of cancer. 

The hemophilias are sex-linked, hereditary diseases 
occurring almost exclusively in males. Although the 
known hemophilic population of thib country is only 
about 25,000, hemophilia constitutes a major national 
health problem for two reasons. First, treatment must 
be continued throughout the lifetime of the patient at 
enormous cost (the current yearly cost to replace the 
missing clotting factor alone is estimated to be in 



excess of $6,000 per patient, or more than $120 
million for the 80 percent of hemophiliacs who can 
benefit from this factor). Second, treatment of the 
disease presents one of the largest single demands upon 
the nation's blood resources. 

Sickle Cell Disease and Related Disorders of the Red 
Blood Cell include sickle cell anemia, Cooley's anemia 
and defects affecting the red blood cell membrane or 
enzyme systems. 

Sickle cell anemia, Cooley's anemia and certain defects 
affecting the red blood cell membrane or enzyme 
systems are all genetically determined and are presently 
incurable, although they may be controlled to varying 
degrees. These disorders lead to premature destruction 
of the red cells in the circulation. Anemia results 
because the bone marrow is unable to produce suffi- 
cient numbers of new cells to keep up with the rate of 
destruction. 

Approximately two million individuals, primarily 
black, carry the sickle cell trait. They are healthy, but 
if two carriers marry, each of their children has a one 
in four chance of having sickle cell anemia, a painful 
and debilitating disorder. About one in 400 black 
babies in this country is born with sickle cell anemia, 
and somewhat less than 50,000 individuals suffer the 
painful episodes known as "crises." 

The cost of caring for a patient with sickle cell disease 
may approach $2,500 to $5,000 a year. The loss of 
time from school, from jobs and the resultant 
psychological and educational problems, make this 
disorder one of high social and economic importance. 

Cooley's anemia results from defective production of 
one of the subunits of the hemoglobin molecule, 
leading to rapid destruction of the red cells. It occurs 
in perhaps 5,000 Americans, largely of Mediterranean 
ancestry. Its victims suffer profound anemia and 
require repeated blood transfusions for survival. As 
with the sickle cell trait, carriers do not have 
symptoms, but offspring may be affected. 

Defects in red cell membranes and red cell enzymes 
also produce anemia. Such defects are relatively rare, 
although one, called glucose-6-phosphate dehydro- 
genase deficiency (G6PD), occurs in about 10 percent 
of black males and less frequently in males of 
Mediterranean ancestry. Most of these individuals are 



B-7 



healthy, but they are sensitive to a variety of 
commonly used drugs and may develop anemia if they 
take them. They also develop anemia with certain 
illnesses. 

Blood Resources for the nation need to be available in 
an adequate supply. High quality blood and blood 
products is essential for the effective treatment of 
many diseases. Whole blood is made up of cellular 
elements dispersed in a fluid medium called plasma. 
The cells consist of red cells to deliver oxygen, platelets 
to stop bleeding, and white cells to fight infection. 
Plasma contains such useful products as albumin, 
immunoglobulins, and clotting factors. 

To give the patient enough of what he needs and when 
he needs it requires recruiting the donor, collecting his 
blood, separating it into its components, detecting and 
eliminating disease-causing agents, matching the 
components for compatibility, and administering it to 
the patient in a fail-safe fashion. 

In the United States, an assemblage of organizations 
(which might be referred to as the blood service 
complex) acquires, processes, stores, delivers and 
administers blood and a variety of blood products. This 
complex has an estimated gross annual income ex- 
ceeding $500 million. It collects about nine million 



pints of blood per year for transfusion. About 25 
percent of this blood is never transfused and much of 
this portion is wasted. 

Whole blood is mostly collected by the blood-banking 
sector of the complex. In addition, the pharmaceutical 
industry, which comprises the other major sector, 
collects about 1.7 million liters of plasma each year, 
mainly for the preparation of plasma fractions (about 
one liter of plasma is present in five units of whole 
Wood). 

Transfusion is not without dangers, one of which is the 
possibility of hepatitis. Approximately 10 to 15 
percent of the whole blood collected by the blood- 
banking sector is obtained from commercial donors. 
This blood accounts for about a quarter to a half of the 
incidence of post-transfusion hepatitis. While nation- 
wide reporting of hepatitis of any origin or type is 
unreliable, it is estimated that each year post-trans- 
fusion hepatitis accounts for 850 deaths, 17,000 
episodes of illness which are often incapacitating for 
weeks to months, and another 100,000 infections 
without symptoms. If we consider only the patients 
who become ill, their average hospital stay is 28 days. 
The dollar cost to the nation approximates $86 million 
per year; costs in terms of human suffering are 
immeasurable. 



B-8 



Definitions of two additional lung disease problems — Pulmonary Vascular Diseases 
and Inhalation Diseases — are given below. 

Pulmonary Vascular Diseases include cor pulmonale, pulmonary hypertension, and 
pulmonary edema. Cor pulmonale refers to enlargement of the heart due 
to an increased workload of the right ventricle resulting from conditions 
which affect the pulmonary circulation. Pulmonary hypertension is char- 
acterized by elevation of pulmonary arterial pressure above normal levels. 
The condition is considered primary when found in the absence of cardiac 
or pulmonary diseases and secondary when associated with these diseases. 
Primary hypertension may be caused by factors such as high altitude and 
low oxygen, or ingestion of certain drugs and chemicals; secondary hyper- 
tension may result from destruction of the pulmonary vascular bed, con- 
genital heart disease, pulmonary vasoconstriction, or congestive heart 
failure. Pulmonary edema, difficult to detect early, is a pathologic 
state in which there is abnormal extravascular storage of fluid in the 
lung. Reliable data on the incidence and prevalence of these diseases 
are not available. However, it has been estimated that cor pulmonale 
alone occurs in 40 percent of cases of emphysema and chronic bronchitis, 
both of which are chronic respiratory diseases of national impact. 

Inhalation Diseases are becoming more prevalent in the United States as indus- 
trialization and the technological age progress. Of all occupational ill- 
nesses, dust inhalation diseases, or pneumoconioses, are the most serious 
health problem. The dusts inhaled are so fine that they escape the natu- 
ral cleansing mechanism of the upper respiratory tract and lodge perma- 
nently in the lungs. If exposure is sufficiently high and prolonged, the 
accumulated particles may cause fibrosis or scarring of the lung tissue 
and in many cases lead to serious disability and even death. One of the 
most serious problems in our country today comes from the direct handling 
of asbestos by some 200,000 workers and by another 3 to 5 million persons 
who are secondarily exposed to the dust. Asbestos is believed to be a 
leading factor in the deaths of over 2,000 persons each year in the U.S. 
The breathing of quartz dust, or silica, is another hazard which gradu- 
ally causes irreversible damage to the lungs. Of the more than 125,000 
workers now engaged in coal mining in the United States, an estimated 10 
to 20 percent have Coal Worker's Pneumoconiosis, or "black lung." Beryl- 
lium, iron, tin, and barium dusts are also hazardous to the lung tissue. 
Pneumoconioses are also caused by organic dusts from plants such as cotton 
(byssinosis) , sugar cane (bagassosis) , and moldy hay (Farmer's lung). 



Definitions of Circulatory Assistance, Respiratory Assistance, and Biomaterials , 
three of the 22 major program elements, are given below. 

Circulatory Assistance to the failing heart may be provided by mechanical circu- 
latory devices which aid or replace the pumping action of the heart. 
There are many types of such devices under development. Some are applied 
externally to the lower extremities in synchrony with the heart beat. 



B-9 



In others, the pumping action of the heart is enhanced by synchronously 
expanding and collapsing a "balloon" positioned in the aorta, the artery 
leading from the heart. On a very limited scale, a few devices have been 
employed which require substantial surgery and the actual positioning of 
a pumping device within the chest. While circulatory assist devices are 
designed to improve the mechanical function of the heart, the apparatus 
generally involves important electronic, pneumatic, hydraulic, and mechan- 
ical systems as well. 



Respiratory Assistance can be provided by mechanical devices (ventilators or 
membrane oxygenators) that support the gas transfer functions of the 
lung when, as a consequence of disease, the lungs are unable to maintain 
proper levels of oxygen and carbon dioxide. Ventilators are devices that 
mechanically inflate the lungs and can deliver increased amounts of oxygen. 
Membrane oxygenators are externally placed "artificial lungs" which are 
connected with the patient's circulatory system. Blood from the patient 
enters the oxygenator, carbon dioxide is removed, the blood is oxygenated 
and then returned to the patient's circulatory system. At present, oxygen- 
ators can only be used safely for several days. Recent experience suggests 
that this method of respiratory assistance holds promise for treatment of 
some patients in acute respiratory failure. 



Biomaterials are synthetic materials which can be implanted in the body and 
used in a variety of medical devices. To be "blood compatible," such 
materials must not cause damage to the various components of blood and 
must not induce blood to clot. In addition, biomaterials must possess 
specific properties suited for specialized functions (for example, gas 
permeability for oxygenation devices) and have minimal risk of causing 
chemical toxicity, allergic reactions, and neoplasia. Several approaches 
are being pursued in the development of suitable biomaterials. Properties 
of the vessel wall have been imitated by "hydrogels," a network structure 
of long polymer chains and water. Blood compatible surfaces can be grafted 
or bonded to a variety of materials which have otherwise promising physical 
properties. Another approach involves the use of human cells which can 
be grown in culture and attached to certain man-made materials to make 
them compatible with blood. Materials can be synthesized which contain 
anticoagulants, clot-dissolving enzymes, and surface-active agents. Com- 
posite materials can be produced which are based on a variety of compo- 
nents mentioned above. 



B-10 





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Public Health Service 

National Institutes of Health 

National Heart and Lung Institute