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JPRS 75251 
5 March 1980 


USSR Report 


SPACE BIOLOGY AND AEROSPACE MEDICINE 


Vol. 14, No. 1, 1980 








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JPRS 75251 


5 March 1980 


USSR REPORT 
Space BroLocy AND AEROSPACE MEDICINE 


Vol. 14, No. 1, 1980 


Complete translation of the Russian-language periodical 
KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA published 
in Moscow by the Meditsina Izdatel'stvo. 


CONTENTS 


Scheduling Work and Rest Periods During Long-Term Space Flights 
(B. S. Alyakrinskiy] 


Use of Mathematical Methods for Predicting Man's Condition During 
Space Flights 
(V. V. Verigo) 


Effects of Flights Differing in Duration on Protein Composition 
of Cosmonauts’ Blood 
(Ye. V. Guseva and R. Yu. Tashpulatov) 


Effects of Unusual Schedules of Daily Activity and Sleep 
Deprivation on Man's Functional State and Work Fitness 
(A. N. Litsov and I. F. Sarayev) 


Effects of Long-Term Space Flights on Reactions of Adrenal Cortex 
and Medulla 
(R. Kvetnyanski et al.) 


Cardiovascular Reaction to Periodic Head-Pelvis Accelerations on 
a Short-Arm Centrifuge 
(I. F. Vil'-Vil'yams and Ye. B. Shul‘zhenko) 


Reaction of Human Blood to Chronic Exposure to Low Doses of 
Carbon Monoxide in a Confined Environment 
(V. V. Zhuravlev et al.) 





PAGE 


15 


21 


30 


36 


43 


°@e [III - USSR - 20-H S&T] 











CONTENTS (continued) 


Probability of Altitude Decompression Disorders When Breathing 
Oxygen Containing Human Waste Gases 
(A. V. Sedov et al.) 


Effect of Hyperoxia on Oxygen Transport Properties of Blood 
(L. A. Ivanov and N. D. Chebotarev) 


External Respiration and Acid-Base Balance of Human Blood During 
Long-Term Antiorthostatic Hypokinesia and in the Recovery Period 
(A. P. Golikov et al.) 


Distinctions in Development of Pyrogenal Fever in Animals 
Following Prolonged Hypokinesia 
(P. V. Vasil'yev et al.) 


Rapid Laboratory Method for Testing Outgasing of Thermostable 
Plastics and Rubber 
(V. D. Yablochkin et al.) 


Effects of 25 and 50 MeV Protons on Human Peripheral Blood 
Lymphocyte Chromosomes in Vitro 
(A. M. Totseva et al.) 


Development of Program for the Control of the Autotrophic 
Component of an Ecological System That Is Closed With Regard 
to Exchange of Gases 

(A. S. Nasonov and V. S. Toroptsov) 


Effect of Sodium Bicarbonate on Reactivity and Trophics of 
Vestibular Analyzer 
(N. I. Arlashchenko) 


Evaluation and Forecasting of Mental Fitness of Flight Personnel 
in the Presence of Neurosis 
(K. K. Iosaliani) 


Dynamics of Stress Reaction of Rats During Experimental 
Hypokinesia Varying in Duration, and Possibility of 
Correction Thereof 

(L. T. Kirichek) 


Effect of Brief Antiorthostatic Hypokinesia on Blood Immunoglobulin 


Content 
(N. N. Mukhina et al.) 


Rat Plasma and Tissue Lipids After a Long-Term Space Flight 
(J. Ahlers et al.) 





Page 


49 


54 


60 


67 


73 


80 


88 


94 


101 


107 


112 


116 





CONTENTS (continued) 


Functional Changes in the Adrenal Cortex During Simulation of 
Stress Situations in the Presence of High Carbon Monoxide Levels 
(S. K. Kalandarov et al.) 


Effect °f Hypoxia and Hypercapnia on Lactate and Pyruvate Levels 
in Rat Blood and Myocardium 
(N. I. Mikhalkina) 
Study of Radioprotective Effect of High-intensity Magnetic Fields 
on Mammalian Cell Cultures 
(Z. Ye. Vnukova) 


Studies of the Effects of Stationary Magnetic Fields on Rat Erythron 
(A. D. Pavlov et al.) 


Petr Kuz'mich Isakov (70th Birthday) 


For the Information of Contributors 


- Cc = 


Page 


120 


125 


130 


134 
141 


143 




















English title 


Russian title 


Editor 


Publishing house 


Place of publication 


Date of publication 


Signed to press 


Copies 


COPYRIGHT 


PUBLICATION DATA 


: SPACE BIOLOGY AND AEROSPACE MEDICINE 
Vol 14, No 1, 1980 


KOSMICHESKAYA BIOLOGIA I 
AVIAKOSMICHESKAYA MEDITSINA, 
Vol 14, No 1, 1980 


0. G. Gazenko 


Meditsina 


Moscow 


January-February 1980 


13 December 1979 


1739 


Kosmicheskaya biologiya i 
aviakosmicheskaya meditsina, 1980 








SURVEYS 


UDC: 613.693 


SCHEDULING WORK AND REST PERIODS DURING LONG-TERM SPACE FLIGHTS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 3-8 


{Article by B. S. Alyakrinskiy, submitted 7 Mar 78] 


[English abstract from source] 


Proper arrangement of work-rest cycles of crewmembers in long-duration space 
light is a practically important task of space ergonomics, a field of science studying 
man + work capacity and methods of its increase. The basic principle of space ergonomics 


assuring bigh efficiency of space crewmembers is io cover every aspect of their activi- 
ties. Of particular importance is the use of Jaws of biorhythmology, in order to select 
candidates least susceptible to desynchronosis and ciosely resembling each other in their 


biorhythmological status. At the present time, work—rest cycles in a prolonged space 
flight should be arranged on a 24-hour basis with a normal day—night alternation, in- 
cluding 8-hour night sleep and 2-hour day rest. Optimization of cosmonauts’ activities 
in space demands that they strictly adhere to the recommended work — rest cycle; this 
cai: be achieved through their highly motivated desire only 


[Text] Elaboration of the principles involved in wise organization of 
labor and rest for representatives of any profession, including cosmonauts, 
is one of the tasks of ergonomics, a scientific direction that now 

deals with studies of work performance (for the purpose of improving its 
efficiency), mainly within "man--machine" systems. Searching for 

sources of increasing efficiency mainly or exclusively within the frame- 
work of an isolated work process is a typical feature in numerous ergonomic 
studies of West European and American researchers. 


Montmollen, one of the leading West European specialists in the field of 
scientific organization of labor [efficiency experts], believes that 


ergonomics is the “technology of linkages in 'man--machine' systems," 


or 


"... more precisely, the technology of factors that characterize inter- 
action between man and machines" [1, p 16]. True, Montmollen immediately 
adds that “ergonomics can be defined as the study of work performance 

for the purpose of improving it" (ibid, p 16), already broadening some- 
what the tasks, with which this discipline deals. However, in spite of 
this stipulation Montmollen, like many other specialists in organization 














of labor, avoids interpretation of ergonomics in his studies in this 
field as the technology of links between man and machines. 


Consideration of ergonomics solely as the technology of relations between 
man and machines reflects a purely pragmatic and strictly utilitarian 
approach to the problem of improving efficiency in the field of computer 
production. Upon closer scrutiny, such an approach is found to be 
overtly unfounded for solving the probiem of improviag work performance, 
since the framework of technology of the links between man and machine 
does not permit (and, in essence, cannot permit) exploration of all the 
possibilities of improving the productivity of labor, all reserves of 
efficiency and all sources of growth of professional productivity. Many 
of these sources are beyond the links between man and machine, beyond 

the confines of man's “work place." Indeed, is it not true that two 
employees, identical in qualifications, working under the same conditions, 
will not produce the same quantity or with the same quality because of 
differences in scheduling of their rest periods and differences in living 
conditions? And is it not true that the same individual does not 

change in his professional efficiency, depending on many factors that 

are far from professional ones (domestic, social and others)? And is 

it not apparent that not only an individual's professional reliability 
and efficiency, but his health, longevity (including occupational), 

level of physical and intellectual development, the entire system of his 
spiritual life depend largely, if not entirely, on the way he has 
organized his life, i.e., the actual work and rest regimen he has 
adopted? 


If this is so, a genuinely scientific approach tc the problem of high 
productivity of labor should take into consideration as many factors as 
possible (within the available range), which determine directly or indi- 
rectly the ongoing efficiency of man. 


The principle of socialistic humanism, according to the very essence of 
which man's endeavors should not cause even the slightest detriment to 

his health or reduce to any extent the possibility of cultural and physical 
development, the possibility of active participation in the nation's 
sociopolitical life, is completely consistent with the requirement of 

a comprehensive approach to purely ergonomic problems. When put on 

such a basis, ergonomics concentrates on man, the real creator and maker, 
for whom work is the enjoyment of “play” of physical and intellectual 
capabilities. And only a science, the representatives of which study with 
equal thoroughness organization of both work itself and leisure, and 

time spent both at work and away from it, i.e., the entire order of 

life of an individual that does work that is needed by society, can 
cause labor to be transformed into a source of enjoyment of the plav 

of physical and intellectual capabilities (and thereby increase its effi- 
ciency). 











Thus, ergonomics as a scientific direction that combines the study of 
the correlation between efficiency of work and a man's life style, the 
entire order of his life and, in particular, the order of his professional 
activity (including factors characterizing interaction between man and 
machine), with the ultimate purpose of increasing the efficiency of 
labor, should include among its main tasks the development of the 
principles for wise organization of both work and leisure (including 
sleep). All of the foregoing also applies in full to the occupation of 
cosmonaut. Moreover, the occupation of a cosmonaut differs from most 
others primarily in that work and leisure, as well as the time spent on 
some sort of activity and time virtually free of such activity, can be 
only relatively, arbitrarily separated under the conditions of space 
flights. Cosmonauts who are aboard an orbital spacecraft, let alone 

an interplanetary one, are cut off from the contacts with people on 
earth, that are customary in form and scope, as well as from the entire 
surroundings of earth. Being dependent entirely on sturdiness of the 
craft, reliability of its numerous systems and, first of all, the life 
support system, even during periods of complete freedom from any duties 
they continue to perform the flight and to participate in fulfilling 

its general objective. Cosmonauts cannot “retreat to the rear from the 
front line of their mission,” they cannot cut themselves off from the 
flight situation. Of course, even sleeping in space is not the same as 
sleeping on earth, since our emotional [spiritual] life never ceases 
enitrely during sleep and always bears the mark of events currently in 
progress. The links between the cosmonaut and the spacecraft are 

really vital, i.e., the welfare and life of the cosmonaut depend entirely 
on them and they cannot be severed at his will. The ties between the 
cosmonaut and a spacecraft are analogous to those of a pilot and his 
aircraft, and the vital need for the latter is also quite obvious. 

An experienced pilot, K. Katichev writes: "In the event of malfunction 
or difficult situation, any other piece of equipment, be it a motor 
vehicle, steam engine or ship, can be stopped, repaired, or else one 

can wait it out until the situation improves, and then continue on one's 
way, and this cannot be said about an aircraft. But whatever the 
problem with an aircraft and no matter how complicated the situation 
could become, a pilot cannot stop a flying aircraft and is compelled to 
find the correct solution making use of all his skill and ability” [2, 

p 24). The vital need for bonds between cosmonauts nd a spacecraft 

is expressed in the special sensitivity of cosmonauts to various types of 
unexpected stimuli that are new to them. This is observed by the cosmo- 
nauts themselves: "In space," states pilot cosmonaut 0. G. Makarov, 
"there is drastically heightened wariness...." [3]. Any danger signal, 
any new stimulus are perceived with equal acuity by all members of a 
spacecraft crew, whether or not they are busy with some sort of work or 
not. Aboard a spacecraft, not only the period of professional activity 
(shift of duty [watch]), but every moment of the cosmonauts’ life, their 
entire life as a whole and its entire order are determined by the process 
of flying, they are “woven into its fabric.” And for expressly this 
reason, assurance of a successful space mission is in essence, an ergo- 
nomic task, this is achieved not only by means of . entific organization 














of work (professional activity) of cosmonauts, but scientific organization 
of their entire schedule in each 24-hour cycle. Hence, it is obvious that 
a thorough analysis must be made of this cycle in the ergonomic aspect. 


The daily cycle is not simply the structure of periods of work, leisure 
and sleep in accordance with the natural alternation of night and day, 
adjusted to this alternation in accordance with considerations of con- 
venience, economy, occupational or some other need. The daily cycle of 
our life is the genetically programmed rhythm of all body functions and 
processes; it is the rhythm of all of the body's vital systems that is 
endogenous in origin. Special studies, which have been conducted mainly 
by specialists in biorhythmology (chronobiology, in the terminology of 
American authors), a science dealing with biological rhythms, have shown 
that any organism that is complex to some extent is a very complicated 
oscillatory system, a distinctive array of numerous rhythms with the 
most diverse frequency, amplitude characteristics, positions of phase, 
range of straying [wandering], etc., and that in this array of rhythms 
the one with a frequency of about 24 h plays a particularly important 
role (hence its name, circadian, occurring approximately every 24 h). 


The special role of circadian rhythms is attributable to the fact that 
they perform the function of a timing device (hence, their name of 
biological clock), that expressly they regulate the process of adapta- 
tion of the body to the environment in the form of its externally mani- 
fested activity (behavioral form of adaptation) and, consequently, they 
watch over the stability of an energy balance that is advantageous to 

the body, an expression of which is the relative stability of sleep and 
waking periods. For this reason, it is not surprising that there is 

a direct and close relationship between the welfare of the body and state 
of its circadian rhythms. 


The state of biorhythmological welfare irberent in healthy man corresponds 
to relative stability of phase architectouics of its circadian rhythms. 
Impairment of these architectonics, i.e., phasic mismatching of circadian 
rhythms of different functions (desynchronosis), is associated with a 
decrease in efficiency, sleep disorders, impaired appetite, mood, 
digestion, appearance of neurological symptoms (severe irritability, patho- 
logical reflexes) and even organic diseases (gastritis, peptic ulcer and 
others). Desynchronosis occurs when changing time zones (transmeridional 
flights), when the customary schedule is altered, when there is unusual 
change in periods of light and darkness (Arctica, Antarctica), under the 
influence of various stress factors and with overfatigue. There is every 
reason to believe that there is a real danger of desynchronosis during 
space flights, whatever their mission. 


In view of the biorhythmological data pertaining to the circadian rhythms 
of the body, it can be stated that successful organization of work and 
leisure in any area of endeavor is achieved only if such organization is 
based on the principle of rhythm, of a rhythm with very definite 








characteristics, first of all, with regard to frequency (duration of period) 
and position of the phase. 


Application cf the rhythm principle is the most important prerequisite for 
rational [wise] organization of man’s life aboard a spacecraft. Asa 
general postulate of space ergonomics, it can be maintained that any 
schedule for cosmonauts that is not governed by a rhythm is 
inacceotable to then. 


However, subordination of the cosmonauts’ life to a rhythm during flight 
is not the oniy prerequisite for rational organization of their work and 
leisure time. It is of exceptional importance for the pace of life 

aboard a spacecraft to be as close as possible to the customary rhythm 
on earth, i.e., a rhythm with a 24-hour period and constant position of 
the phase on a 24-hour scale. Im this respect, the best variant of a 
space day would be a day that is identical to the day at the launching 
pad, provided that the cosmonauts had completely adjusted to the time 
zone at the sp*cepwrt. The problem of man's adjustment to a day that is 
not the same as o «arth cannot yet be considered definitively solved. 
There are data tc . « effect that man can adjust to changes in length of 
a day (other than ¢« 4), out there are few such data, and thev were ob- 
tained from studies conducted under different and, occasionally, radi- 
cally different conditions. We cannot fail to concur with V. Bruce [4] 
that highly organized beings have difficulty adjusting to cycles, the 
period of which differs significantly from 24 h. This thesis of V. Bruce 
was confirmed in experiments on hamsters [4], in whom cycles with periods 
of 23.5, 24, 24.5 and 25 h (with equally long periods of light and dark- 
ness) altered the physiological sleep--waking rhythms, while cycles 

with periods of 22 and 23 h did not alter them. We studied adjustment 
of subjects (5 men in all) to 23- and 25-h days (1971-1972). Both the 
23-h and 25-h cycles of sleep and waking state were not adopted by the 
subjects. In studies with shorter days, there was distinct manifestation 
of integrity of the 24-h periodicity of body temperature and excretion of 
potassium from the 7th-8th day on. It should be noted that the most 
marked signs of absence of adjustment to a 23-h day were demonstrable at 
the last stage of the experiment, when the difference between experi- 
mental and 24-h days diminished progressively, rather than at the time 
when it reached a maximum [12 h). 


In the studies with a 25-h day, in addition to lack of adjustment to 

such a cycle, the subjects presented disturbances of phase architectonics 
of the circadian system. In the oldest subject (32 years of age), this 
was manifested by the finding that the lowest body temperature began 

to consistently shift from the start of the waking period to the end 

after the 5th day, while the maximum began to shift toward the start of 
the waking period, starting on the 7th day. As a result of such migration 
of phases of temperature rhythm, they shifted considerably in relation to 
the phases of the rhythm of potassium excretion, which is an indication 

of internal desynchronosis. 





Use of a 24-h day aboard a spacecraft, which would be synchronous with 
the daily cycle at the spaceport, would mean that all crew members sleep 
at the same time. Scheduling of sleep should provide for at least 7 h 
duration. In any case (with the exception of emergencies and other 
extcaordinary situation:), the cosmonauts must adhere strictly to the 
sleep schedule, whether or not they want to sleep during the hours sche- 
duled for it. Sleep should be viewed as a part of the flight program 
that is just as important as scientific experiments, observations, 
working with onboard systems, etc. Performing work during the time 
reserved for sleep shculd te categorically excluded. There is no need 
to specially discuss the importance of comfort of the place where the 
crew sleeps; it should be outfitted with due consideration of the 

factor of weightlessness and habits of each crew member. 


The schedule for the day should provide, in addition to 7-8 h of sleep, 
mandatory rest for 2 h (during the waking peiord), organization of which 
is defined in advance (on the ground) by the individuals responsible for 
preparing the flight program (with the participation of specialists-- 
physicians, psychologists, hygienists, etc.). The rest program should 
be prepared with mandatory consideration of the individuality of each 

| participant in the flight, his desires in this respect, and it should be 
backed up by an adequate amount of appropriate material (books, film strips 
{or slides], tape recordings, table games and others). 


A programmed schedule for the day (with due consideration of all the 
listed requirements) will reduce significantly the influence of the 
negative factors of long-term space flights on cosmonauts. However, this 
can be achieved only if the suggested schedule for work and rest is 
strictly kept. Punctuality in following the work and rest schedule can 
be achieved only if there is full awareness of the need and substantia- 
tion of such a requirement, a set on the vital importance of adher: ng 
meticulously to the program of the onboard day. Formation of such a 

set is not a single act, it is a lengthy and painstaking process. A set 
cannot be formed as a result of simple instruction, periodic reminders 

or a preliminary talk. It develops only if an individual not only 

is aware of the importance of adhering meticulously to the suggested 

work and rest schedule, not only understands the contents of this require- 
ment, but is convinced of its vital importance. And conviction is 
usually formed in an individual over long segments of his life, as a 
result of intensive internal work which necessarily involves the intellect 
and emotions. Here, it is opportune to stress once more the advantage 

of the above-formuiated general conception of ergonomics, within the 
framework of which studies are made not only of the "man--machine--object 
of labor--work environment" system, not only the links between components 
in this system, not only the work process per se, but the entire order of 
a man's life, everything that pertains to both work and free time. For 
expressly this reason, the problem of formation of the required sets, in 
particular, the set toward absolute adherence of cosmonauts te the 








prescribed work and rest schedule, which is based on the principles of 
scientific organization of man's life in space, is an ergonomic problen. 


From this point of view, the problem of organizing the work place, 
recreation areas, places for sleeping and individual rest, as well as the 
problem of organizing joint work by crew members, minimizing the dele- 
terious effects of the extreme flight conditions and, finally, the problem 
of using, if necessary, unusual daily sleep-waking rhythms aboard the 
spacecraft, are also ergonomic problems. The last mentioned probiem 
merits special discussion. 


At the present stage of development of cosmonautics, such distinctive 
flight elements as launching time, precession and deorbit shaping, 
landing time and any emergency situations could preclude (and in many 
cases have done so) scheduling the life of cosmonauts following the 
example on earth. True, at the present time, actually all the conditions 
to assure such scheduling, even for long flights, already exist, as 
indicated by the flights aboard Soyuz-26 and Soyuz~27 spacecraft, as 

well as Salyut-6 orbital space station. Elimination of the negative 
influence of disruptions in the daily cycle aboard a spacecraft (i.e., 
organizing the life of cosmonauts according to the grouvd-based schedule) 
does not, however, eliminate the danger of desynchronosis. As indicated 
by material in the literature and our findings, desynchronosis can occur 
(and does indeed occur) when man is exposed to the stress of the most 
diverse negative factors. We can include among such factors weightless- 
ness as well (and, apparently, all of the other extreme factors of space 
flights). For this reason, it is of utmost importance to elaborate 
measures to reduce as much as possible the danger of desynchronosis, 
especially in the case of a lengthy flight. There are facts that indi- 
cate that resistance to the adverse effect of disruptions of the customary 
daily schedule is quite individual. "Substantial differences have been 
noted in the capacity to adjust to altered work--rest cycles: some 
subjects adjusted rapidly to unusual cycles, while others were either 
totally incapable of such adjustment or had great difficulty in adjusting" 
[5, p 165]. For expressly this reason, proper screening of candidates 
for long-term space flights is important. 


American specialists recommend that crew members be compatible, with re- 
gard to circadian rhythms, in screening cosmonauts and manning crews [5]. 
This recommendation can be followed only if the flight program provides 
for simultaneous sleep of the cosmonauts, if conditions are provided for 
mutual induction that is instrumental in maintaining the same daily 
rhythm of life for all cosmonauts. But if the cosmonauts sleep at 
different times, their compatibility with regard to circadian rhythms 
would not be very important. 


Biorhythmological screening of candidates for space flights should be 
performed as early as possible, the best time (if possible) being prior 

to their enlistment as cosmonauts. Properly gathered history, the results 
of routine observation by specialists (physicians, training supervisors), 




















friends, relatives, etc., are very important. One must record the dis- 
tinctions of sleep under any circumstances (how fast the candidate falls 
asleep and wakes up, whether sleep is continuous or intermittent, his 
capacity to fall asleep under unusual conditions, etc.). 


This approach to training of spacecraft crews conforms entirely with the 
conception of space ergonomics, the area of competence of which extends 
to the entire order of cosmonauts’ life. This conception also includes 
the requirement for “biorhythmological" arrangement of the interior of a 
spacecraft. If we agree that maintaining the circadian rhythm of man 
depends largely on strict organization of the system of time sensors, we 
should also agree that, in space, where there is always the danger of de- 
synchronosis, “build-up” of time sensors, saturation of the internal 
environment of the spacecraft with these sensors, in particular, those 
that simulate not only the daily dynamics of light, temperature, humidity 
inherent in earth, but seasonal fluctuations of these factors, acquire 
special significance. 


BIBLIOGRAPHY 


l. Montmollen, M. "'Man--Machine' Systems," Moscow, 1973. 


2. Katichev, K. VESTN. VOZDUSH. FLOTA [Vestnik of the Air Corps], 
No 9, 1955, pp 24-33. 


3. Apenchenko, Yu. PRAVDA, 13 1 1975. 


4, Bruce, V. in "The Biological Clock," Moscow, 1964, pp 60-90. 


>. "Man Involved in Long-Term Spacecraft, " Moscow, 1974. 











DC: 613.693-037:51 


USE OF MATHEMATICAL METHODS FOR PREDICTING MAN'S CONDITION DURING SPACE 
FLIGHTS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 9-12 


[Article by V. V. Verigo, submitted 28 Feb 78] 


[English abstract from source] 


Possibilities of applying mathematical methods and computers to solve problenis 
of predicting the human health state in space flight are discussed. The use of methods 
of simulation modelling is recommended. Examples of their application are described. 


[Text] The task of predicting man's healthy status and efficiency during 
space flights continues to be one of the most interesting and important 
tasks for modern space biology and medicine [1]. Previously obtained 
results [2, 3] warrant the belief that the need to develop mathematical 
methods of predicting dynamic processes inthe human body would stimulate 
research of both applied and general biological importance. The 
development of reliable and comprehensive forecasting methods may also be 
useful to clinical medicine. It would be difficult to overestimate the 
importance of automaced forecasting of man's condition and reliability 

as an element of an integral biotechnological complex when designing and 
predicting the development of new space equipment, including equipment 
for active control of healthy status and work fitness of cosmonauts. The 
objective of controlling man's health status under extreme conditions is 
in essence a question of situational control, the principles of which have 
been described [4, 5]. Situational control deals with the behavior and 
synthesis of organizing systems implemented by means of man-machine 
complexes. However, we shall not touch upon the problems of automated 
classification of a situation, decision making and correction of 

current and future condition of cosmonauts, and shall limit ourselves 
only to a discussion of questions of using mathematical methods and 
computers for evaluation and prediction purposes. 


There are three routes for the use of mathematical methods and computers 
to forecast man's condition during space flights. The first is closely 























related to the most widely used method of expert forecasting. Here, intui- 
tion and experience of the team of experts play the leading role in 
forecasting, while the task for the mathematical service is merely to 
provide for optimum working conditions [mode]. The experts make use of 
both current information received in the course of a flight and data 
stored in banks, which contain information about prior flights and ground- 
based tests. The choice end formation of data arrays, use of statistical 
algorithms to compare and contrast them, as well as other necessary opera- 
tions are performed by means of a system of interactive dialog. 


The distinction of the variants of dialog systems that we are using and 
developing is that they allow an expert without special mathematical 
knowledge to work with data arrays and processing algorithms in an inter- 
active mode on the basis of a rather low level computer language. On the 
other hand, there must be a possibility for on-line development of the 
set of procedures for processing data by specialist-mathematicians on the 
basis of develope i algorithmic languages. 


It was possible to meet both these requirements by breaking down the dialog 
system into two program components. One of them, the logic structure of 
which is made up of a combination of choice of data and choice of method 
of manipulating with them, provides for interaction between experts and 
the computer. The interactive dialog is conducted at will, through a 
display or printer, on a language that is as close as possible to a 
natural one. The other (monitor) program component makes it possible 

to conducted on-line adjustment of the program modulus and transcribe it 
into the library of absolute moduluses in the place of prior modification, 
after which it becomes accessible to the expert. There has been experi- 
ence with the use of such a system for processing major complex, ground- 
based experiments. The choice of attributes of bases of data from 
natural and ground-based studies is made together with the experts. 


Another direction in the use of mathematical methods is the use of an 
extensive group of forecasting algorithms, which are based on extrapolation 
of time series. With the use thereof, forecasts were made of pulse rate 
and respiration rate by means of nonlinear discrete filters and other 
methods. The results of using some of them were reported previously [6]. 
Figure 1 illustrates examples of forecasting the pulse rate of cosmonauts 
by means of regression equations, the coefficients of which were assessed 
dynamically using the method of stochastic approximation. The possibili- 
ties and range of application of this group of forecasting methods are 

not yet entirely apparent. In spite of the fact that satisfactory results 
are obtained in a number of cases, there is reason to believe that their 
potential is rather limited, if only because the mechanisms of adaptation 
and possible pathogenesis of physiological systems under new conditions 
are obviously not taken into consideration in the forecasting process. 
Nevertheless, we can hope that they will be a useful supplement to the 
traditional methods of medical experts, while some of them could be used 
for automatic analysis and forecasting of the condition of cosmonauts, 
particularly with the use of onboard equipment. 








10 








29 


u,¥ 100 -— Ung 




















+ — 
flight days a he ae ee | 
Figure l. Figure 2. 
Forecasting pulse rate (PR) of two Simulation of Ca, Mg and K excre- 
crew members aboard Salyut-1l tion after hypertensive calcium 
spacecraft. Solid line, actual load. Solid line, simulation; 
values; dash line, forecast. The dash line, actual values. 
dots refer to the forecast after 6 X-axis, time (h); y-axis, 
days, triangles--after 12 days and Y-axis, excretion (% of normal) 


x's after 14 days of flight 


The third of the directions is simulation modeling. The theoretical bases 
of this method have been described previously [9]. Imitation modeling 
has been used with success in the national economy [7, 8]. The specifics 
of using a simulation model lies in multiple reproduction of a dynamic 
process. The process of setting conditions characterizing concrete 
realization thereof (initial conditions, exogenous factors, parameters of 
the model) is called setting a "scenario" in existing terminology. For 
simulation modeling in physiology, preparation of scenarios includes 
setting parameters determining the status or individual distinctions of 
the subject or specific physiological system, setting changes in time 

of exogenous conditions and, in the case uf various hypotheses on physio- 
logical mechanisms, choice of hypothesis. This work is a creative pro- 
cess performed by an expert physiologist with the consultation and colla- 
boration of a mathematician. At the present time, work is in progress to 
automate this procedure. 


Current information and the results of prior studies are used in a dual 
manner in simulation modeling. In the first place, they are needed to 
formulate the assignment (scenario). In the second place, they can be 
used to identify unknown or approximately set parameters of models. 

For this purpose, a special module [block] was developed for identifica- 
tion of models of dynamic systems with a finite number of degrees of free- 
dom, which is used to simulate physiological systems, life support systems, 
as well as for radiobiological ani ecological studies. 


Let us consider some examples of operation of the variants of simulation 
models developed to date, which illustrate their capabilities to some extent. 


ll 














A major study [10], based on abun- 
dant experimental and clinical data 


Orthostatic test served as the basis for the simula- 

















Time of elevation tion model of fluid-electrolyte 
: metabolism. However, for the pur- 
V ’ 
a Sa tpmin 1/Ci, a = = ~ pose of forecasting the results of 
Standing! 7.4 10 Ww functional tests in the course 














of simulating weightlessness on 

a b the ground (hypokinesia), a radical 
modification thereof was required. 
The most significant modification 

was consideration of transport of 























































































































wo? i > < - r a5 Yes bivalent cations of calcium and 
on | _ | | magnesium. Figure 2 shows a com- 
g +) - ad 7 4 parison of model data to the results 
| : of studies conducted by A. I. 
fl | fyi go - Grigor'yev, G. A. Kozyrevskiy and 
|__@ 4 827 CyCzi_ @ 4 a S other physiologists who participated 
| Wie a4 2 ee"? g ro Ae in this work. They simulated a 
108 108 | | change as a function of time in 
excretion of several electrolytes 
| | 106 - after a hypertensive calcium load. 
= 999; 5 100 We can see that simulation of 
_ : | excretion of bivalent cations 
. poo has a yielded satisfactory results. The 
£ 2\+— 92}-—+ poorer results for excretion of 
. § hs . 2 Beak potassium can be attributed to the 
“e 0 & tc ~“* 0 & # #2tc vagueness of many aspects of the 
physiological mechanism of potassium 
Figure 3. excretion by the kidneys, which 
Simulation of changes in parameters exists at the present time. Per- 
of respiration after orthostatic test haps, even rather approximate simu- 
a) model without chemoreceptors lation of processes of potassium 
b) effects of arterial transport will require not only 
chemoreceptors description of central mechanisms 


of regulation thereof, but 
differentiated consideration of the role of different segments of the neph- 
ron, which has not yet been reflected in the model. 


In studies of the influence of space flight factors on the system of ex- 
ternal respiration, due consideration was given to the fact that they 
affect the most appreciably the dynamics of processes in the lungs. 
Accordingly, for the first time a model was developed, which rendered 
pulmonary gas exchange as a process in a system with rhythmically changing 
flow of blood and gases and the lungs as an aggregate of many functional 
units operating over a wide range of modes. Figure 3 illustrates the 
results of simulation of processes in the external respiration system 
during an orthostatic test. It was assumed that ascent occurs instan- 
taneously at time t = 0. Elevation of pressure in the right atrium and 


12 








increase in pulmonary blood flow Q were calcuated by means of a simulation 
model of circulation. Evaluation was made of increase in functional 
residual lung volume (RV) and decrease in elasticity of the external res- 
piratory system (1/C;), on the assumption that all these changes occur 
much faster than the changes in parameters of gas exchange. The curves in 
Figure 3 illustrate variants of simulation of the orthostatic test on 

the assumption of a constant chemical "drive," i.e., in the absence of 
afferent signal from arterial chemoreceptors and with consideration of 
their influence. The results of modeling indicate, in particular, that 
arterial chemoreceptors play an important role in stabilizing the composi- 
tion of arterial blood in cases of sudden changes in parameters of the 
system of external respiration. The results of simulation modeling of 

the erythropoietic system have already been discussed in this journal 

{1l, 12]. 


Thus, it is quite probable that it will be expedient, in the near future, 
to supplement the software presently available to medical experts with 
simulation models and, perhaps, algorithms of the extrapolation type. Thus, 
use of such models enables medical men to scan the dynamics of changes 

in the parameters studied within a short period of time, on the basis of 
assumptions of possible mechanisms of pathogenesis, and to compare various 
hypotheses. In addition, it is possible to evaluate parameters that are 
difficult to measure from the findings of observations. Simulation 
modeling, which combines well the advantages of heuristic medical methods 
and formal mathematical procedures, is very promising in our opinion, and 
it has undergone recent development in the United States [13]. 


BIBLIOGRAPHY 


1. Gazenko, 0. G., and Verigo, V. V. | KOSMICHESKAYA BIOL. [Space Biology], 
No 2, 1979, pp 3-7. 


2. “Fundamentals of Space Biology and Medicine,” Moscow, Vol 2, Bk l, 
1975, p 257. 


3. Verigo, V. V., et al. in "Matematicheskaya teoriya biologicheskikh 
protsessov" [Mathematical Theory of Biological Processes], Kaliningrad, 
1976, pp 202-203. 


4. Pospelov, D. A. TEKHN. KIBERNETIKA [Technical Cybernetics], No 2, 
1971, pp 10-17. 


5. Klykov, Yu. I. “Situational Control of Large Systems," Moscow, 1974. 
6. Vasil'yev, V. K., et al. KOSMICHESKAYA BIOL., No 2, 1977, pp 42-47. 
7. Moiseyev, N. N., et al. EKONOMIKA I ORGANIZATSIYA PROM. PR-VA 


[Economics and Organization of Industrial Production], No 6, 1973, 
pp 39-46. 


13 





12. 


13. 








Akopyan, R. A. in "Voprosy kibernetiki" [Problems of Cybernetics], 
Moscow, Vyp 28, 1977, pp 110-11/. 


Shannon, R. “Art and Science of Simulation Modeling of Systems," 
Moscow, 1978. 


Guyton, A. C.; Colman, T. G.; Granger, H. J.; et al. ANN. REV. PHYSIOL. 
Vol 34, 1972, pp 13-46. 


Verigo, V. V., and Smirnova, T. M. KOSMICHESKAYA BIOL., No 1, 1978, 
pp 31-35. 


Idem, Ibid, No 2, 1979, pp 13-18. 


TRANS. ASME., Ser G, Vol 95, No 3, 1973. 


14 











EXPERIMENTAL AND GENERAL THEORETICAL RESEARCH 
UDC: 612.124-057:656.7 


EFFECTS OF FLIGHTS DIFFERING IN DURATION ON PROTEIN COMPOSITION OF 
COSMONAUTS' BLOOD 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDTTSINA in Russian 
No 1, 1980, pp 13-17 


{Article by Ye. V. Guseva and R. Yu. Tashpulatov, submitted 3 May 78] 


{English abstract from source] 


Aiter space flights of varying duration different adaptive changes in the protein 
composition of cosmonaut’s blood were detected. A short-term 2-day ilight induced a 
decline of gamma-globulin (immunoglobulins G and A) and B,-glycoprotein fractions. 
Longer-term 16- and 18-day flights caused an increase in albumin and most globulin 
iractions. A long-duration 49-day flight brought about an increase in the content of 
Cye- and C,-factors of the complement and immunoglobulins G. A and M. Return of the 
blood protein composition to the normal after prolonged space flights takes a long period 
of time 


[Text] It is known that there was a reliable increase in total serum 
proteins in astronauts who had flown aboard the Apollo series of space- 
craft, after their return to earth [1]. A constant increase was observed 
in haptoglobin, cerulloplasmin, acid a),-glycoprotein, as well as changes 
in the fraction of G2-macroglobulin. The substantial difference in the 
case of the 59-day mission aboard Skylab, as compared to previous flights, 
was retention of a constant level of blood proteins [2]. 


A change in blood protein synthesis, manifested by an increase in globulin 
fraction and appearance of a mildly positive reaction for C-reactive pro- 
tein, was also observed in cosmonauts after long-term flights [3]. After 
the 6-day flight on the ASTP program, some increase in albumin content and 
decrease in globulin content, chiefly referable to gamma globulins, were 
demonstrated [4]. 


The objective of our studies included the following: 1) study of the effect 
of occupational training of cosmonauts on protein composition of blood 

and setting physiological norms for levels of different protein fractions 
in this group of people; 2) comparative study of the nature of changes in 


15 











protein spectrum and duration of the recovery period following flights 
differing in duration. 


We submit below the results of studying the protein composition of blood 
of cosmonauts who participated in flights lasting 2, 16, 18 and 49 days 
aboard Salyut-3 and Salyut-5 orbital stations and in their transport 
spacecraft of the Soyuz type. 


Methods 


The main protein fractions of blood serum were assayed by the method of 
radial immunodiffusion in M- and LC-partigenic dishes of the Beringwerk 
Firm (FRG), in which there were monospecific sera against blood plasma 
proteins in an agar-gel layer. Solutions of human blood serum containing 
specific amounts of the tested protein fractions were used as standards 
(standards of the Beringwerk Firm). We determine the amount of total 
blood protein by menas of the biuret reaction. The results obtained 

were processed by methods of variational statistics [5]. 


During the professional training of cosmonauts, their blood was analyzed 
many t.mes in order to obtain individual background data. This made it 
possibie to establish the range of the physiological norms for different 
blood proteins of 25 cosmonauts, as well as to demonstrate some typical 
differences in levels thereof. 


Results and Discussion 





The mean indices of most protein fractions of blood differed negligibly 

in our group of cosmonauts (see Table), and they usually presented a 
narrower range of fluctuation than the corresponding means of healthy 
people [6]. We found relatively higher mean indices for total protein 

and fractions of prealbumin, ceruloplasmin, a2-macroglobulin, §8-lipoprotein, 
transferrin and immunoglobulin D (IgD). The mean values for G.-globulin 
and albumin were below and above the physiological range, respectively. 


A narrower range of fluctuations between the bottom and top limit of 
normal was a typical finding in the protein spectrum of cosmonauts’ blood, 
as compared to analogous indices in other healthy individuals. The higher 
top range of total blood protein in cosmonauts is probably attributable 

to the fact that the range of fluctuation of concentration of albumin, a 
protein that constitutes the largest fraction of all proteins assayed, 

was also beyond the range of mean fluctuations of this protein taken as 
the norm for healthy people. We demonstrated lower ranges for G,.- and 
C3c-globulins and higher ones for G2-macroglobulin. 


We made a comparative evaluation of the data referable to 2-, 16- and 18- 


day (cumulative data), as well as the 49-day space flight (see Figure). 
Individual blood serum proteins were assayed before the flight (background 


16 


























values, taken as 100%), then on the Ist, 7th, 14th and 29th postflight days. 
We submit here only statistically reliable fluctuations of results. 
Mean indices of protein composition of cosmonauts’ blood (ag/100 mf serum) 
—____Horm _[6] Cosmonauts 
Protein fraction a - 7 _ 
Pr2albumin 25 10—40 Kt) 27—33 
Albumin 4400 3500—5500 6345 5809 —695. 
“reactive protein <1i.2 1 

2sG) ycoprotein ¥ 20 1S—30 19 18—2I 
Acid Q4-qlycoprotein 90 55—140 74 68— 80 
flastog ie0 50—220 2 0214 

; 121 102—i4! 
&2-Macroglobulin 240 150-350 284 197 —371 
“globulin 40 W—55 28 24-31 

“1 popro ein 300 250—800 76 686 — 846 

i rin 295 200 —400 352 318—397 
Se | in 110 8—140 AS 77—99 
Ceng 20—50 33 29-38 

Ig3 1250 800—1 800 1146 1052—1i240 

Igh 210 9—450 144 182--216 

a 125 0-0 , i114 103—135 

tal protein 70 6 os 0 80 13-8 5 

AYSumik /globulin ‘9 1 8—2.0 19 | «(1a 20 




















Before the flight, the levels of blood protein fractions were within the 
range of the adopted norms in all cosmonauts. We only found a higher 
level of total blood protein and albumin. Perhaps, the high concentra- 
tion of blood serum protein (mainly albumin) constitutes « protein re- 
serve for other cells of the body. The negligible individual deviations 
of the blood protein spectrum were not associated with appearance of any 
disturbances referable to metabolic processes and immune reactions. The 
levels of Ig of all classes were within the usual physiological range. 
There was no C-reactive protein. Thus, in the preflight period we 
demonstrated activation only of synthesis of albumin, a protein that 
plays a substantial role in fluid metabolism, maintenance of osmotic 
pressure, transport of various ions and pigments, and performing the 
function of protein reserve and nutrition. 


Analysis of postflight data enabled us to demonstrate some differences in 
the changes in blood proteins as a function of duration of space flights. 
It must be noted that we failed to demonstrate statistically reliable 
changes in 8-lipoprotein, acid a,-glycoprotein, IgD and C-reactive 
protein in any of the cosmonauts after the flights, and therefore data 
pertaining to the relevant proteins are not illustrated in the Figure. 


After completion of a 2-day space flight, we observed a decline of levels 
of three protein fractions of blood: 82-glycoprotein I (to 78.4%), IgG 


17 




















(to 57.5%) and IgA (to 67.7%). We demonstrated a decrease in IgG and IgA 
gamma globulin fractions, which play a vital part in immunological processes 
in the human body, can appareatly be interpreted as the body's adaptive 
reaction to accelerations.and weightlessness, which are factors that 
accompany space flights whatever their duration. 













































































































































































“COTM 

(iim 

Seton Ml Ih 

HMO DOI obi Ot 
ga” : 

hm 4 : il | 
eM) CTL) LS CM 


Days in postflight period 


Protein fractions of cosmonauts’ blood serum after 2- (a), 
16- and 18- (b, total data) and 49-day (c) space flights (only 
statistically reliable fluctuations are shown) 


1) total protein 6) ceruloplasmin 11) Cy-globulin 
2) prealbumin 7) haptoglobin 12) IgG 

3) albumin 8) a2-macroglobulin 13) IgA 

4) 82-glycoprotein I 9) G.-globulin 14) IgM 

5) transferrin 10) Cs.-globulin 


Very different changes in blood protein spectrum were observed after the 
16- and 18-day flights. On the first postflight day, we demonstrated 
higher levels of prealbumin, albumin, as well as globulin fractions--62- 
glycoprotein I, haptoglobulin, G.-globulin, C3.~-globulin, IgG, IgA and 
IgM--against a background of higher total protein content of blood. Such 
changes can be interpreted as adaptive reactions of the body to pro- 


longed weightlessness and the set of other factors associated with the 
longer flight. 


After the flight factors ceased to exist there was restoration of the level 
of most blood protein fractions within a relatively short time. Thus, only 


18 











four globulin fractions were above the preflight levels on the 7th post- 
flight day, and only IgA was above the preflight level on the 14th day. 
The protein composition of cosmonauts" blood became ent‘rely normal by 

the 28th day of the postflight period. The only exceptaon was the change 
in level of transferrin, the protein responsible for iron metabolism in 
the body: we found a gradual decrease in content thereof (on the 14th-28th 
postflight days). 


After completion of the 49-day flight, we demonstrated changes only in the 
globulin fraction of blood. In essence, there was a change in gamma 
globulin fraction of proteins (IgG, IgA, IgM) and 8,;-globulins (C3-- and 
Cy-factors of the complement system), i.e., proteins involved in immune 
reactions. It should be stressed that we found a very high concentration 
of all of the above-listed blood proteins, as well as ceruloplasmin and G,- 
globulin, immediately after the flight. The levels of these proteins in 
blood were significantly higher than the top range of the physiological 
norm. Probably, after 49 days of weightlessness the initial changes in 
protein spectrum of blood inherent in the early stages of space flights 
had been corrected, since the adaptation process was almost completely 
ended. 


There appeared a tendency toward further normalization of the blood protein 
spectrum of cosmonauts on the 7th postflight day: only the levels of four 
giobulin fractions remained elevated. 


A drastic change in blood protein spectrum was observed on the 14th post- 
flight day: increased levels of prealbumin and seven globulin fractions. 
At expressly this time, most of them reached maximum levels. The changes 
occurring at this stage can be interpreted as readaptation to earth 
after the long-term flight. We should call attention to the postflight 
decline (starting on the 14th day) of G2-macroglobin level. Such changes 
were also found in American astronauts [1]. 


On the 28th day after the 49-day flight, the concentration of B2-glyco- 
protein I and IgM remained high. Evidently, more time was required for 
normalization of these proteins. 


Summarizing the results of our study of protein composition of biood of 
cosmonauts after they returned from flights differing in duration, it 

can be concluded that the least changes in functional state of the body 
occurred after short space flights. Space flights lasting 16 and 18 days 
were associated with impairment of the largest number of protein fractions. 
After returning from the even longer, 49-day flight, the quantitative 
changes in some protein fractions became even more marked, while other 
parameters were normalized. 





These data indicate that the typical reaction of the body to prolonged 
exposure to space flight factors is adaptation, adjustment to new condi- 
tions, and the adaptive changes in blood protein composition in cosmonauts 
increase gradually with increase in duration of exposure to space flight 


19 

















factors (weightlessness), and they affect the maximum number of protein 
fractions after 16-18 days into the flight. Further increase in duration 
of exposure to space flight factors leads to restoration of preflight 
levels of some blood proteins and significant increase in concentration 
of others (C3.- and Cy-globulins, IgG, IgA and IgM). 


On the basis of analysis of the obtained data on increase in Ig and two 
fractions of the complement system of cosmonauts in the postflight 

period (16-, 18- and 49-day missions) and data in the litezature [7, 8] 
concerning destruction of skeletal muscles of cosmonauts ‘a weightlessness, 
it was assumed that the products of atrophy of skeletal muscles could 
lead to synthesis of autoantibodies to striated muscles. We demonstrated 
Similar adaptive changes in blood protein composition of polar workers 
after long stays under the extreme conditions of the Antarctic continent. 


The established fact of postflight change in G42-globulin fractions (hapto- 
globin, G.-globulin, ceruloplasmin), i.e., the blood proteins that are 
actively involved in regulation of metabolic processes in the body, is 
also of importance. Evidently, the impaired level of blood proteins 
could indicate that a long-term space flight induces a substantial change 
in processes of protein, carbohydrate and lipid metabolism. 


BiBLIOGRAPHY 
l. Fisher, C. L., and Gill, C. AEROSPACE MED., Vol 43, 1972, p 850. 
2. Kimzey, S. L., et al. Ibid, Vol 47, 1976, p 383. 
3. Legen'kov, V. 1. "Dynamics of Peripheral Blood Indices in Cosmonauts 


During fheir Professional Training and Space Flights," author abstract 
of candidatorial dissertation, Moscow, 1975. 


~~ 
. 


Gurovskiy, N. N.; Gazenko, 0. G.; Yegorov, b. B.; et al. in 
"Kosmicheskiye polety na korablyakh ‘Soyuz'" [Space Flights Aboard 
the Soyuz Series of Spacecraft], Moscow, 1976, p 381. 


5. Ashmarin, I. P., and Vorob'yev, A. A. "Statistical Methods in 
Microbiological Research," Leningrad, 1962. 


6. Schultze, H. E., and Heremans, J. F. "Molecular Biology of Human 
Proteins," New York, Vol 1, 1966. 


7. Bryanov, I. I.; Yemel'yanov, M. D.; Matveyev, A. D.; et al. in 
"Kosmicheskiye polety na korablyakh ‘Soyuz'," Moscow, 1976, p 195. 


8. Tashpulatov, R. Yu.; Guseva, Ye. V.; and Petrosov, V. V. 
ZH. MIKROBIOL. [Journal of Microbiology], No 2, 1978, p 19. 


20 











UDC: 612.821.7"41" 


EFFECTS OF UNUSUAL SCHEDULES OF DAILY ACTIVITY AND SLEEP DEPRIVATION ON 
MAN'S FUNCTIONAL STATE AND WORK FITNESS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVLAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 17-23 


[Article by A. N. Litsov and I. F. Sarayev, submitted 30 Aug 78] 


{English abstract from source] 


— Physiological functions, work capacity and sleep characteristics of six healihy test 
subjects were studied for 30 days. The test subjects adhered to one of the three di‘ 
ierent regimens (1 — sleep from 2.00 a.m. to 10.00 a. m., 2 — sleep irom 6.00 p. m. 


to 2.00 a. m., and 3 — sleep from 10.00 a.m. to 6.00 p.m.) which were aggravated 
by 64 hr or 72 hr vigilance during the experiment. The studies demonstrated general and 
spectiic changes in physiolegical functions, work capacity and sleep closely associated 
with the fact how far work—rest cycles were shifted and how long they were applied. 
Prolonged vigilance caused similar changes in physiological functions. work capacity 
and sleep. The test subjects showed very poor tolerance to an alteration in the work—rest 
cycle combined with sleep deprivation. 


[Text] Plotting a daily cyclogram of man's activities on the basis of a 
24-h sleep-waking rhythm is one of the main prerequisites for retaining 
the initial fitness for work [efficiency] and health. In this regard, 
the study of the distinctions of man's adaptation to different variants 
of sleep-waking schedules and elaboration, on the basis of these data, of 
optimum functional cyclograms can be considered to be one of the most 
important tasks for occupational medicine [1-3]. The main objective of 
this report is to discuss the distinctions of man's adjustment to some 
variants of the sleep-waking schedule, complicated by prolonged and 
continuous wakefulness at one of the stages of the study. 





Methods 


These studies* were conducted for 30 days on 6 healthy male subjects 
ranging in age from 28 to 42 years. There were two series of studies, in 





*These studies were conducted in collaboration with V. N. Artishuk, Yu. V. 
Yakushkov and Yu. A. Shpatenko. 


21 











each of which three men participated concurrently. The daily cyclogram for 
subjects’ activity in both series provided for a 24-h sleep-waking rhythm, 
constant 8-h watch duty shifts, each of which was taken by one subject at 
a time and, consequently, the first subject remained awake from 1000 to 
0200 hours and slept from 0200 to 1000 hours; the second subject was 
awake from 0200 to 1800 hours and slept from 1800 to 0200 hours; the 
third subject stayed awake from 1800 to 1000 min and slept from 1000 to 
1800 hours. At one of the stages of the study, each subject was 
scheduled for continuous duty for 64 h (first series) and 72 h (second 
series) without sleep. On the first daily schedule, the continuous 

duty was scheduled for the 3d day of the study, on the second one it was 
on the 13th day and on the third, it was scheduled for the 23d day. 


The activities of the subjectswere the same in both series, and they 

were strictly specified in the daily schedule, including the following: 
communications and radio engineering work, autonomous astronavigation, 
control of dynamic object, operational servicing, visual observation, 
testing functions of the visual analyzer, and others. In the course of the 
studies, we examined the circadian rhythm of some physiological functions 
(pulse rate, EEG rhythms), mental efficiency (simple and complex motor 
reactions), dynamics of higher nervous activity, dynamics of sleep (EEG 
Stages, pulse, actogram, subjective evaluations) and behavioral reactions. 


Results and Discussion 


In the first series of studies, each subject followed the same work and 
rest schedule for 30 days (witn the exception of 64 hours of continuous 
wakefulness). According to the obtained data, the changes in sleep- 
waking cycles induced signs of external and internal desynchronization of 
most of the indices studied in all subjects inthis series (particularly 
on the first days); the magnitude and nature of these changes were 
closely related to the magnitude of phase shift in the daily cycles and 
effect of prolonged sleep deprivation. Thus, we see in Figure 1 that 

the daily pulse curves of subject F-v follow the rhythm of the new 
schedule, with minor deviations manifested only by some decline of ampli- 
tude of fluctuation of physiological parameters in the late evening hours, 
on the 3d day on the schedule that provided for a minor shift of cycles. 
There were also virtually insignificant deviations in the dynamics of his 
EEG (see Figure 1), parameters of efficiency and sleep characteristics 
(Tables 1 and 2). 





In subject S-ko (schedule involving 5-h shift of sleep-waking cycles), the 
deviations of pulse parameters were more marked on the first days (see 
Figure 1); the EEG presented some increase in representation of 6- and 6- 
waves and exaltation of a-rhythm in response to stimuli, while the 
dynamics of psychophysiological tests were indicative of general deterio- 
ration, particularly at night. Normalization of all parameters was 
postponed to the 6th-7th day, and up to 12 days for some tests (see Tablel). 


~ 


22 






























































P/min 
S$ 28 


























































































i 
4 
20 - 
> 151 
a! > 
371 3 
3 05 4_ a 
° 7 . 
Pw 
60 
4” 
& : 
Oy 60 - 
hd 
Q 
A 1 
% 
: as 
. oo -— 2. he ; =. a oe A 
Time of day (hours) Time of day (hours) 
Figure l. Figure 2. 

24-h dynamics of pulse and EEG 24-h dynamics of pulse and EEG 
rhythms in first series of studies rhythms in second series of studies 
a,b,c) subjects F-v, S-ko and B-sh a,b,c) subjects Kh-v, S-k and S-n 

1-7) 3d, 7th-lOth, 12th, 14th- 1-7) 3d, 7th, 12th, 16th, 23d- 
16th, 20th-22d, 25th-26th, 24th, 26th, 29th days of 
28th-29th days of study study 

8) continuous wakefuiness 8) continuous wakefulness 
(mean data for 2 days) (mean data for 3 days) 


In both figures: x-axis, time of day (hours); K, ratio between EEG rhythms: 
ae arb.U, arbitrary units; P, pulse. 


23 











Sleep of S-ko was impaired, both qualitatively and quantitatively, in subject 
S-ko (see Table 2). 


Table 1. Dynamics of efficiency indices for subjects in the first series 
















































































of studies 
~ Day of : F-y S-ko B-sh 
study|/hours} A | Bic!]alspicial|sie 
1 376 479 | 4,86 | 365 | 476 | 3,70] 207 | 496 | 5,35 
‘ 4 372 562 | 5.14] 356 | 526 | 2'79| 344 | 396 | 5.33 
& a 510 | 3.59 | 364 | 512 | 2.18! 370 | 631 | 8.06 
12 341 582 | 5.901 275 | 491 2.07 | 418 | 565 | 6.86 
1 365 574 | 3,03] 330 | 481 | 2.61 o72 | 505 | 5.13 
. 4 369 48 |3.13| 314 | 538 | 2.59| 375 | 375 | 4.60 
& 359 49 |3.53| 290 | 527 | 2.68| 381 | 536 | 5.87 
12 430 574 | 2.93] 349 | 549 | 3.54] 331 | 601 | 4.74 
| 
342 a8 | 5,72) — | _ | _ | 983 | 451 | 4.68 
- 4 371 498 |3:31' — | — | — | 307 | 454 | 4.26 
8 341 473 4.95 | 373 | 487 |2.8:; —| — | — 
12 377 555 6.16 338 | 508 |/300; —~| — | — 
! » - — | 365 | 481 | 2,03] 306 | 454 | 2.17 
- 4 nat i — | 377 | 652 | 2:17] 314 | 457 | 3.07 
8 444 638 |2.57/| 288 | 40 |289) ~| —~ |] — 
12 285 456 | 4.20| 342 i ttt om 1 om | 
i i 
! 281 470 «15.65 | 251 | 414 | 2.22] 320 | 501 | 3.70 
- 4 311 468 | 4.64, 284 | 450 | 2.12| 373 | 480 | 3.42 
8 350 450 | 5.46 | 300 | 450 | 2.02] 341 | 504 | 4,77 
12 336 516 | 4.84} 296 | 440 | 2.07) 331 | 470 | 3.05 
! 370 581 15.50] 330 | 437 | 2.37] 303 | 646 | 3.23 
- 4 353 505 1455} — | — | — | 283 | 460 | 3.34 
x 356 444 | 4.54! 298 | 447 | 2.27] 410 | 754 | 2.63 
12 353 | 470 | 4.42] 225 | 444 ' 2.31] 414 | G8i | 3.68 
: | j | 
l 
300 asa | 5.39| — | — | — | 260 | 407 | 3.88 
- 4 283 484 | 4.50) — | — | - | 994) 487 | 2.82 
x 294 «7 | 401! 254 | 435 | 1.931 396 | 570 | 3.51 
12 328 | 492 |6.17| 310 | 397 | 1.96] 361 | 491 | 3.25 





























Key (for this and Table 4): 
A) simple motor reaction (ms) 
B) reaction of choice between two alternatives (ms) 
C) solving arithmetic problems (s) 


Even more marked changes were noted in subject B-sh (schedule with 1l-h 
shift of sleep-waking cycles). According to Figure 1, his daily pulse 
curves were distorted and flattened. The curves presented two minimums, 


24 











one of which was at the usual sleep time (from 0200 to 0600) and the other 
corresponded to the imposed sleeping time (from 1200 to 1500 hours). 


Table 2. Dynamics of sleep indices for subjects in the first series of 











studies 
F-v | S-ko | B-sh 
days 
Index ‘ Pa °o ° ° * o ° : Q . 
o ? nN o -. ” oe : 7. “ ; 1 
iyitetalitiyela] i] éfels 





Falling asieep, min 7} 12) 8 9} 62] 96] 27} 40; 48; 10) 13; 10 
Sleep time, min 360} 455) 448} 440] 368) 353) 425) 423; 292) 365) 426) 445 
Movements per hour | 3.3! 3,2) 3,6) 3.9] 5.1] 5,2) 4.3 6.2) 4.9] 5,8) 5.2) 5.1 
% calm 5-min periods) 78.0) 76 .0| 72,6|75.0/ 61 .5| 67,5] 70,0| 67 .3| 68.4) 58,2) 52,8) 65,2 
Footnotes for this and Table 3: 


*Sleep from 0200 to 1000 hours **k*) Sleep from 1000 to 1800 hours 
**Sleep from 1800 to 0200 hours 






































Restoration of typical daily dynamics was observed by the 18th-20th day. 
The EEG dynamics presented significantly increased representation of 6- 
and 6-rhythms, dysrhythmia and other disturbances in tracing pattern for 

a long time. On the first day, sleep was superficial, intermittent and 
lasted a total of about 4-5 h. Then the sleep indices gradually recovered 
and duration increased, reaching 7-7.5 h by the 20th-23d day (see Table 2). 


Remaining continuously awake for 64 h was associated with distinct and 
unidirectional change in most of the parameters studied in all subjects, 
regardless of when the waking period began. Thus, the pulse curves for 
subject F-v evened out in amplitude with retention of 24-h cycle. By 
the end of the first and, particularly, the second day we observed a 
decrease in energy of a- and $-rhythms and increase in 6- and 6-rhythms. 
Efficiency indices worsened, particularly at night (by 50-60%). In subject 
S-ko, the pulse rate became the same in the daytime and at night. The 
EEG showed a decrease in G-rhythm and increase in §- and 6-potentials in 
the early morning hours. Efficiency indices worsened mainly during the 
night (by 60-802). 


In subject B-sh, the curves for pulse rate retained the pattern of the new 
schedule during continuous wakefulness. The EEG present build-up of 8)- 
and B2-rhythms, which was generally indicative of retention of a high 
level of wakefulness in this subject, in spite of the prolonged sleep 
deprivation. The latency periods of sensorimotor reactions and erroneous 
actions increased, reaching a maximum by the end of the second day. 


25 




















Immediately after the period of prolonged continuous wakefulness, sleep 
improved significantly in all subjects. Time required to fall asleep 

was brief in all cases (1-2 min), sleep was not interrupted, being asso- 
ciated with minimal motor activity and prevalence of deep, slow-wave 
Stages. On the next days, the sleep parameters of all subjects remained 
negligibly diminished (by no more than 5-10%). We observed rapid restora- 
tion of other parameters also. Thus, in F-v, the pulse curves conformed 
with the new schedule onthe 2d-3d day, the EEG indices on the lst-2d day 
and mental efficiency on the 3d-5th day. There was even faster readjust- 
ment of parameters in S-ko. Even less marked deviations were observed in 
subject B-sh. 


Thus, according to the findings from the first series of studies, it can 
be concluded that, in the presence of an unusual work and rest schedule, 
at first there is desynchronization of functions and then readjustment 
thereof. We found that the rate of readjustment is closely related to 
the extent of the shift in work and rest schedule [1, 4-6]. 


Table 3. Dynamics of sleep indices for subjects in second series of 














Z studies 
Kh-v | S-k S-n 
days 
Index ‘ . 

e ° ° ° eo 

. ° ry ° e ° ° 
° N So . e N Co e ° o“ => 
bad - ™ Re) . ” iy o wo c o 
rn . | ? § * » = 
j ' rte) | 1 Zr) - | ! e ~ 
7 ~ - ce i — N - t=) - a) 





























Falling asleep, min' 10 18; 15| 40} 10) 30; 5) 20; 5| 17] 38| 43 



































Sleep time, min 380| 272} 219] 255] 360] 410] 445} 355| 330] 385| 309] 370 

Movenents per hour |6.1/ 9.4; 7,8] 8.0] 6.8] 5.3! 6.1| 8.8! 6,7] 8.9; &.3| 7.0 

% calm 5=min 57.5 | 46.2| 54,0] 56,0] 59.0] 65.1 | 64,0| 54.3/ 51.3] 51,2] 57,0] 61.2 
periods 











In the second series of studies, we examined the dynamics of vital func- 
tions using 72-h continuous wakefulness followed by an 8-h shift of sleep- 
waking schedule. According to the data obtained (Figure 2), pulse rate 
conformed rather rapidly, in phase and amplitude, with the new schedule 
in subject Kh-v (for the first 3 days there was a 3-h shift in sleep and 
waking cycles). The EEG parameters and efficiency coincided almost 
immediately with the new schedule, and sleep became good by the 3d day, 
lasting a total of 7-7.5 h (see Table 3). In subject S-k (5h shift of 
schedule), the pulse indices were desynchronized for the first days 
(flattened and distorted in phase and amplitude). The curves conformed 
entirely with the new schedule by the 6th-8th day. On the first days, 
slow 6- and é-waves appeared on the EEG, and there was a decline in 


26 








frequency of a-rhythm; these disturbances persisted for 2-3 days. Effi- 
ciency indices deteriorated according to most tests, and restoration 
took 8 to 12 days. On the first few days, this subject took a long time 
to fall asleep (up to 60-80 min); sleep was superficial and he woke up 
frequently. Asin the first series, improvement of sleep occurred on 
about the 7th-12th day. 


Table 4. Dynamics of efficiency indices for subjects in the second series 
















































































of studies 
Day of Waking Kh-v S-k S-n 
study | hours| A B jc}jal{lspi[cjalsjc 
| 
181 230 13.12] 963 | 655 | 5.90! 231 | 439 4.66 
, 4 291 596 | 3.09| 283 | 616 16.30; — | — | ~— 
8 A ~ ~— | 204 | 612 | 5.30] 274 | 572 | 4.1 
12 : 277 422 14,04] 311 | — | 3.90 960 | 514 | 3.57 
209 392 | 2.611 317 | 550 | 3.43] 165 | 430 | 3.50 
6 4 196 480 '255] — _— — 195 | 425 | 3.22 
8 223 461 | 2.53] 390 | 613 | 5.29! 182 | 494 | 3/28 
12 185 517 | 2.60] 232 | 598 | 4.84| 159 | 442 | 4/04 
1 | oe 47 |2.50! 303 | 571 | 6.32] 150 | 367 | 3.74 
- 4 296 339 | 2.30] 484 | 460 |620| 165 | 337 | 2'86 
8 246 387 (263; — | — | — | 156 | 385 | 3'61 
12 291 317 |2.99| 230] — | 6,03! 168 | 410 | 3°17 
309 414 | 2.42] 287 | 655 | 4.56) 203 | 356 | 4.00 
” 4 223 421 | 2:77} 382 | 583 14.19] 189 | 437 | 5.46 
8 288 487 | 2'56| 364; 534 | 5.22! 285 | 450 | 3.20 
! 12 237 477-1251 | 254 | 672 | 6.25) 177 | 351 | 3°45 
200 440 | 2.46] 299 | 674 | 4.35! 154 | 356 | 3.21 
- 4 325 456 | 2.69] 269 | 646 | 4.35| 200 | 442 | 3°13 
& 326 593 | 2.49! 317 | 652 | 4.44; 220 | 415 13.50 
12 292 581 | 2.36! 419 | 886 | 4.07 | 199 | 462 | 3'29 7 
972 467 | 2,51 | 208 | 490 | 4.08] 135 | 323 | 3.44 
- 4 224 412 | 235! 290 | 616 | 4.89] 204 | 331 | 2/83 
& 212 420 | 2'63| 348 | 582 15.92} —~ | — | 2 
12 235 327 | 2.64) 177 | 637 | 6.29; 221 | 347 | 2.60 
221 452 | 2,90] 192 | 675 | 4,26] 186 | 387 | 4.16 
- 4 189 391 | 2.51 | 201 | 632 | 388] 202 | 436 | 3°71 
8 206 aur} 2.52] 23) — Jai33] — | — | 2 
12 239 444 7 2,60 | 168 | 578 | 4.67| 217 | 431 | 3.86 





























The results on subject S-n were somewhat different from the indices for 
other subjects; his work and rest schedule was changed every 4-5 days (see 
Figure 2). The daily cycle was disrupted in this subject with each change 


27 

















of schedule and then it was restored; recovery became more difficult after 
each change of schedule. The EEg was characterized by rapid adjustment 

to the new schedule at first, but then there was gradual appearance of 
signs of persistent deviations: build-up in representation of slow waves, 
exaltation of G-rhyt!im, appearance of marked EEG dysrhythmia and others. 
Analogous changes were also noted in dynamics of efficiency indices 

(Table 4), which were also characterized by marked fluctuation [undulance] 
and severe deterioration in the daytime and improvement (distortion) at 
night. This subject present significant disturbances in dynamics of sleep. 





The dynamics of the indices studied (24-h cycles, efficiency) changed 
during 72-h continuous wakefulness in about the same way as in the preced- 
ing series of studies. 


Immediately after continuous wakefulness, all subjects in this series 
slept well (in spite of the new schedule), fell asleep rapidly, with low 
motor activity and somewhac increased number of deep slow-wave stages. 
Sleep lasted a total of up to 8-8.5 h. On subsequent days, the parameters 
changed drastically in all subjects. Thus, in Kh-v (schedule involving 
ll-h shift of sleep-waking cycles) the daily pulse curves retained their 
stereotype for the first few days (latent readjustment stage), then 
flattened and became distorted (stage of visible readjustment), and it is 
only toward the end of the study period that they conformed closer to the 
new schedule. EEG dynamics presented stable disturbances (slow waves, 
dysrhythmia, exaltation) for a long time. Efficiency indices improved 
immediately after the period of prolonged wakefulness (latent period of 
readjustment) and then worsened, the maximum changes occurring by the 
22d-26th day of the study. There was also significant impairment of sleep 
during this period in this subject. 


In spite of the use of a close to normal sleep-waking schedule after depri- 
vation of sleep, subject S-k presented marked deviations of most of the 
parameters studied: circadian rhythm of pulse rate, dynamics of efficiency 
and sleep characteristics, which persisted almost to the end of the study 
(see Figure 2, Tables 3 and 4). 


Thus, according to the results of the second series, the changes in dynamics 
of physiological functions, efficiency parameters and sleep dynamics were 
more marked than in the first series. 





To sum up the findings as a whole, it can be concluded that man's adjust- 
ment to a new sleep-waking schedule is a rather complex process that con- 
sists of several stages [4-5]. At the same time, our studies revealed that 
there is a distinct correlation between readjustment of the human body and 
magnitude of shift in sleep-waking cycles, time and number of changes 

from one schedule to another. We found that prolonged sleep deprivation 
affected the dynamics of readjustment of physiological functions and effi- 
ciency. It was established that man tolerates the use of the same types 


28 








of schedules under conditions of prolonged sleep deprivation much better. 
The change in sleep-waking schedules combined with prolonged sleep depri- 
vation was tolerated much worse by the subjects and had an adverse effect 
on their functional state and efficiency. Such schedules should be 

used with great caution. 


BIBLIOGRAPHY 


1. Alyakrinskiy, B. S. “Fundamentals of Scientific Organization of 
Cosmonaut Work and Rest," Moscow, 1975. 


2. Nicholson, A. AEROSPACE MED., Vol 43, 1972, pp 253-257. 

3. Strugholod, H. APPL. NECH. [sic] REV., Vol 22, 1969, p 1339. 

4. Kuznetsov, 0. N.; Lebedev, V.I.; and Litsov, A. N. in “Problemy 
inzhenernoy psikhologii” [Problems of Engineering Psychology], 
Moscow, Vyp 1, Pt 2, 1968, pp 262-267. 


5. Litsov, A. N. KOSMICHESKAYA BIOL. [Space Biology], No 4, 1969, 
pp 59-65. 


6. Higgins, E. A.; McKenzie, G. M.; Vaughan, G. A.; et al. in “Aerospace 
Medical Association Annual Scientific Meeting Preprints," San Francisco, 
1975, pp 37-38. 


29 














EFFECTS OF LONG-TERM SPACE FLIGHTS ON REACTIONS OF ADRENAL CORTEX AND 
MEDULLA 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 24-27 


[Article by R. Kvetnyanski, R. A. Tigranyan, T. Torda, D. Repchekova, 
Ye. Yakhnova and K. Murgash, submitted 16 Jan 78] 


{English abstract from source] 


Concentrations of corticosteron and catecholamines, and activities of catecholami- 
ne synthesizing enzymes, tyrosine hydroxylase, dopamine-f-hydroxylase and phenyl et- 
hane! amine-\-methyl-transferase, were measured in the adrenals of rats flown for 19.5 
days aboard the biosatellite Cosmos-782, synchronous and vivarium control animals sac- 
rificed on R -O and R + 26 days. The flown rats showed a moderate but significant 
increase in the adrenal weight, corticosteron concentration and tyrosine hydroxylase 
activity on R--O day. These parameters returned to the normal on R-+-26 day. This 
data gives evidence that the adrenocortical and sympathoadrenal systems were not sig- 
nificantly stimulated by the space flight effects; therefore, weightlessness cannot be con- 
sidered as a potent stressful agent, although its some stressogenic cliect has been 
documented. 


[Text] It has been established by numerous studies that activation of the 
adrenosympathetic and adrenocortical systems is one of the main symptoms 

of a stress reaction. Our objective here was to study the stressogenicity 
of long-term space flights to rats, on the basis of assaying corticoids, 
catecholamines and enzyme-synthesizing catecholamines in the adrenals. 


Methods 


We examined male Wistar-SPF rats 6-10 h and 26 days after a 19.5-day 
flight aboard the Cosmos-782 biosatellite. 


The results obtained on flight rats were compared to the findings on two 
other groups of animals--intact (contro!) and from synchronous experiment, 
in which all flight conditions, with the exception of weightlessness, were 
simulated on the ground. 


30 





After decapitating the rats, the adrenals were rapidly extracted, cleaned, 
weighed and frozen in liquid nitrogen. They were stored in a frozen 
state for 6-12 days. As shown by studies conducted before the space 
flight, this period of storage of samples in a frozen state did not have 
an appreciable influence on the parameters measured. 


The left adrenal was homogenized in 600 pl 0.25 M saccharose. To 100 pl 
homogenate we added 2.4 pf 0.4 N HC1Oy, to precipitate proteins, and the 
supernatant was used to assay epinephrine and norepinephrine using a 
modification of the method of Euler and Lishajke [1]. The remainder of 
the homogenate (500 uL) was centrifuged under refrigeration for 20 min 
at 10,000 G, and we took 200ulLof the supernatant to assay tyrosine 
hydroxylase (TH) activity by the radioisotope method of Nagatsu et al. 
[2], and 50 uk for measurement of activity of phenylethanolamine-N- 
methyltransferase (PNMT) by the method of Axelrod [3]. 


The right adrenal was homogenized with 1 mf 1% Triton-X in 0.05 M tris-lcl 
buffer (pH 7.4). To determine the activity of dopamine-f-hydroxylase (DBH) 
we took 150 uf homogenate, diluted it in the above buffer so that 100 pl 
would contain 0.4 mg adrenal tissue, centrifuged it 1 day later at 4°C 

and 10,000 G, and determined DBH activity in 100 ul supernatant according 
to Molinoff et al. [4]. Of the remaining homogenate, we used 350 wf to 
assay corticosterone in the adrenals by the modified method of 

Guillemin et al. [5]. 


Results and Discussion 


We found enlargement of the adrenals in rats sacrificed immediately after 
landing, as compared to intact animals and the synchronous group (Figure 1). 
The concentration of corticosterone in the adrenals of flight rats did not 
differ reliably from the indices of intact animals, although it was 

reliably higher than in the synchronous group (Figure 2). Neither the 
weight of the adrenals nor concentration of corticosterone differed from 

the control in rits sacrificed 26 days after landing. 


We observed a tendency toward decrease in epinephrine content of the 
adrenals of flight rats, as compared to the control, but there was no 
reliable decrease; the same tendency was demonstrated in rats of the syn- 
chronous group (Figure 3). There was also no change in norepinephrine 
content of the adrenals of flight animals, as compared to the other groups. 
The concentration of catecholamines in the adrenals showed no appreciable 
change from the levels for different groups 26 days after landing, 

although it was generally higher. 


TH activity was reliably higher in the adrenals of flight rats decapitated 
immediately after landing, as compared to intact animals and those in the 
synchronous experiment (Figure 4). TH activity was restored to the control 
level 26 days after the space flight. 


31 














of ‘ ih 
io : 
» | 
Zor 
Sm 
3 { 
~~ : } 
:” 
ol. 






































Figure 1. 
Weight of rat adrenals. X's indi- 
cate statistical reliability in re- 
lation to control group (P<0.05); 
the 3 dots refer to the same in re- 
lation to synchronous group (P<0.01) 























250 r Z Z 
a0} - 
> er 
br 
c 100+ > 
° 
a] 
wz %0r 
*] 
gU-44i | 
” 72929 ,-ue 
Figure 2. 


Corticosterone concentration in rat 
adrenals. The results are given as 
percentage of control (control is 

8 ug/g tissue); the dot indicates 
Statistical reliability in relation 
to synchronous group (P<0.05) 


In Figures 1-4, the results are given as Mtm (data for 4-5 animals), 


and the following key applies: 


I) immediately after landing of Cosmos-782 biosatellite 
Il) 26 days after landing of the biosatellite 






































1) control 2) flight 
i afi 
sa | 
eof (ing li 
> dale la 





Figure 3. 


Catecholamine content of rat adrenals. 


White columns, epinephrine; black 
ones, norepinephrine 





3) synchronous experiment 


Or i f 
xanax 6e8@ 
ner 
ei 
a 
ain ned 
3 | 
Cini 
not 
as} 
0 












































eet 423 


Figure 4. 
TH activity in rat adrenals. The 
3 x's refer to statistical relia- 
bility in relation to control 
(P<0.01) and 3 dots, in relation 
to synchronous group (P<0.01) 


DBH activity increased immediately after landing in the adrenals of flight 
rats, as compared to both control groups; however, in view of the small 
number of animals examined (5 rats), the increase was unreliable. DBH 
activity was onthe level of control values 26 days after landing. No 
appreciable change in PNMT activity was demonstrable in the adrenals of 
rats in the flight group. 


As we know, activation of the rat adrenal cortex is manifested by increased 
secretion of corticosterone and level thereof in the adrenals, as well as 
increased weight of the adrenals in the case of a prolonged action. In 
flight rats we found a reliable icnrease in weight of the adrenals and 
concentration of corticosterone in them, as compared to animals in the 
synchronous control. After a 22-day flight aboard Cosmos-605 biosatellite, 
an increase in weight of adrenals and size of nuclei in the fascicular 

zone of the adrenals was also observed in rats [6]. However, as compared 
to other models of stress, the increase in corticosterone content of the 
adrenals of flight rats was less marked, as also indicated by the fact 

that there was no reliable increase in corticosterone in adrenals of 

flight animals, as compared to the control. A reliable increase in con- 
centration of corticosterone in the adrenals was demonstrated, for example, 
in rats submitted to traumatization in a Noble-Collip drum [7] and after 
immobilization [8]. However, it must be borne in mind that, in our experi- 
ment, the animals were decapitated 6-10 h after landing, which is a long 
enough time for termination of acute activation of the adrenal cortex 
during the landing maneuver. On the other hand, this effect may be 

related to the manipulations on the animals before they were sacrificed. 
However, the increase in weight of the adrenals, which required longer 
exposure to the stress factor, may indicate that not only the landing 
maneuver but, perhaps, weightlessness for 19.5 days of the flight activated 
the adrenal cortex. 


There was # reliable change in catecholamine content of the adrenals of 
flight rats. Epinephrine level presented a tendency toward decline, as 
compared to the control. This finding can be attributed either to the 
negligible intensity of the stressogenic factor, or increased synthesis 
of catecholamines in the adrenals under the influence of a long-term 
impulse. A decline in concentration of catecholamines in the adrenals had 
been observed following acute immobilization [9]; after 3 weeks of 

daily immobilization (which corresponds in our study to the period spent 
in space), the epinephrine content was no longer low, and there was an 
appreciable increase in norepinephrine content of the adrenals of rats 
submitted to stress [9]. 


In order to find an answer to this question, we determined the activity of 
enzyme-synthesizing catecholamines, higher levels of which (mainly TH) 

are indicative of intensified catecholamine metabolism. We found a reliable 
increase in TH activity in the adrenals of flight rats, as compared to the 
control and synchronous groups, which may be indicative of prolonged 


33 











stimulation of the adrenal medulla, not only during landing and the period 
between landing and decapitation of the rats, but during the space flight. 


There was also an increase in activity of adrenal DBH in the flight rats; 
however, in view of the small number of animals in the groups (5 in each), 
this increase is only on the borderline of reliability. PNMT activity of 
the adrenals did not change under the influence of the space flight, and 
this may be the result of insignificant stressogenicity of this factor, 
i.e., insufficient activation of the hypophysioadrenocortical axis, on which 
the increase in PNMT activity depends significantly [10, 11]. TH and DBH 
were already on the control level 26 days after landing. It was demon- 
strated that, under the influence of stress, the increased metabolism of 
the protein of TH reverted to normal 1-2 weeks after immobilization, i.e., 
the half-time for drop in activity constituted about 3 days [12]. Chuang 
et al. [13] cite the same half-time for decline of TH activity after cold 
stress. 


An increase in activity of enzyme-synthesizing catecholamines was cbserved 
following various stress factors [10, 12, 14-16]. Repeated immobilization 
led to 2-4-fold increase in TH and DBH activity in rat adrenals [17]. 
Weightlessness lasting for 19.5 days of the space flight also caused a 
reliable increase in adrenal TH activity, but only by 25%, while DBH 
activity did not increase reliably. 


The above data warrant the conclusion that weightlessness has in insigni- 
ficant but statistically reliable effect on activation of the adreno- 
sympathetic system of rats. 


BIBLIOGRAPHY 


l. Euler, U. S. V., and Lishajko, F. ACTA PHYSIOL. SCAND., Vol 51, 1961, 
pp 348-355. 


2. Nagatsu, T.; Levitt, M.; and Udenfriend, S. ANALYT. BIOCHEM., Vol 9, 
1964, pp 122-126. 


3. Axelrod, J. J. BIOL. CHEM., Vol 237, 1962, pp 1657-1660. 


4. Molinoff, P. B.; Weinshilboum, R.; and Axelrod, J. J. PHARMACOL. EXP. 
THER., Vol 178, 1971, pp 425-431. 


5. Guillemin, R.; Clayton, G. W.; Lipscomb, H. S.; et al. J. LAB. CLIN. 
MED., Vol 53, 1959, pp 830-832. 


6. Portugalov, V. V.; Savina, Ye. A.; Kaplanskiy, A. S.; et al. 
KOSMICHESKAYA BIOL. [Space Biology], No 4, 1976, pp 19-25. 


34 








ll. 


12. 


13. 


14, 


15. 


16. 


17. 


Mikulaj, L., and Kvetnansky, R. PHYSIOL. BOHEMOSLOV., Vol 15, 1966, 
pp 439-446. 


Mikulaj, L., and Mitro, A. in “Neurohumoral and Metabolic Aspects of 
Injury," New York, 1973, pp 631-638. 


Kvetnansky, R., and Mikulaj, L. ENDOCRINOLOGY, Vol 87, 1970, 
pp 738-743. 


Kvetnansky, R. in "Frontiers in Catecholamine Research," New York, 
1973, pp 223-229. 


Wurtman, R. J., and Axelrod, J. J. BIOL. CHEM., Vol 241, 1966, 
pp 2301-2305. 


Kvetnansky, R.; Weise, V. K.; and Kopin, I. J. ENDOCRINOLOGY, Vol 87, 
1970, pp 744-749. 


Chuang, D.; Zsilla, G.; and Costa, E. MOLEC. PHARMACOL., Vol ll, 
1975, pp 784-794. 


Axelrod, J.; Mueller, R. A.; Henry, J. P.; et al. NATURE, Vol 225, 
1970, pp 1059-1060. 


Kvetnansky, R.; Gewirtz, G. P.; Weise, V. K.; et al. MOLEC. 
PHARMACOL., Vol 7, 1971, pp 81-86. 


Maengwyn-Davies, G. D.; Johnson, D. G.; Thoa, N. B.; et al. 
PSYCHOPHARMACOLOGIA (Berlin), Vol 28, 1973, pp 339-350. 


Pfeifer, W. D. in “Catecholamines and Stress," ed. by E. Usdin, R. 
Kvetnansky and I. J. Kopin, Oxford, 1976, pp 265-270. 


35 








UDC: 612.17.014.477-063 


CARDIOVASCULAR REACTION TO PERIODIC HEAD-PELVIS ACCELERATIONS ON A 
SHORT-ARM CENTRIFUGE 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 27-31 


[Article by I. F. Vil'-Vil'yams and Ye. B. Shul'zhenko, submitted 24 Jun 77] 


{English abstract from source] 


As a result of 370 experiments in a 2 m-arm centrifuge, high human tolerance 
to acceleration of +-0.8, 1.2 and 1.6G, (at the level of feet) was demonsirated. Car- 
diovascular reactions depended on the value, duration and frequency of acceleration 
eaposures. Cardiovascular responses included, primarily, changes in regional circulation 
of the legs. 


[Text] At the present stage of development of space medicine, there is 
discussion of the possibility of simulating gravitational loads by means 
of an onboard short-arm centrifuge (SAC) for the purpose of preventing 
the effects of deconditioning of the body during long-term weightlessness. 
It is known that rotation on an SAC under hypokinetic conditions increased 
man's orthostatic stability according to the index of frequency of 
syncopes [1]. However, the physiological effects of accelerations with 

a high gravitation gradient, which occur during rotation on an SAC, have 
been little-studied. The foreign research in this direction deals mainly 
with man's endurance of single exposure to accelerations with a high 
gravitational gradient [2, 3]. At the same time, it is considered 
expedient, in developing regimens for preventive rotation on an SAC, to 
provide for the possibility of periodically repeated use thereof. 


Our objective here was to investigate the reactions of the cardiovascular 


system to various modes of periodic exposure to head-pelvis accelerations 
on an SAC. 


36 














Methods 


A total of 370 tests were made with the participation of 14 healthy male 
volunteers using a centrifuge with a 2-m arm [radius]. The subjects were 
in supine position on the centrifuge platform, the Z axis coinciding with 
the radius of rotation, and the magnitude of the latter depended on the 
height of the subject, constituting a mean of 1.74 m. The axis of rota- 
tion traversed the bridge of the nose on eye level. Head-pelvis acce- 
lerations of 0.8, 1.2 and 1.6 Gz were generated at foot level. The 
resultant accelerations constituted 1.3, 1.6 and 1.9 G,, respectively. The 
gravitational gradient over the body constituted 100% according to esti- 
mates made by the method in [2]. In order to minimize the vestibular 
effects of Coriolis accelerations, the subject's head was immobilized, 
motor activity and flow of visual stimuli were limited (housing over the 
head portion of the centrifuge, rotation in a darkened room). 


Three series of studies were conducted. The first series (121 cases) was 
methodical [7]; in the second and third series (249 rotations), the subjects 
were submitted to accelerations varying in frequency, 2 and 3 times a day 
(see Table), during 3-day immersion based on the principle of "dry" 
submerging [4]. In order to maintain the same overall duration of ex- 
posure to accelerations during the day (120 min), the duration of rotation 
varied in the second and third series. 


In all of the studies, we recorded the EKG in the leads of Neb followed 
by estimation of heart rate (HR) and photoplethysmograms (PPG) of the 
vessels of the ear lobe. In the third series and, partially, in the 
second, we recorded the PPG of vessels of the first toe and determined 
systemic arterial pressure (AP) in the brachial region according to 
Korotkov sounds and tachooscillograms. 


All of the data were submitted to processing by the method of variation 
statistics of Student-Fisher. The differences were considered reliable 
at P<0.05. 


Results and Discussion 


These studies revealed that the human body is highly resistant to accelera- 
tions with a steep gravitational gradient over the body. Only in 9 of the 
370 cases (2.4%) was rotation on the SAC stopped prematurely because the 
subjects felt poorly, complaining of general weakness and unpleasant 
sensations in the epigastric region. In eight cases, these subjective 
feelings coincided with development of cardiac dysrhythmia in the form of 
relative bradycardia, which preceded a decrease in PPG amplitude of ear 
lobe vessels to 25~30% of the base level. In one case, rotation was 
stopped because of appearance of multiple left ventricle extrasystoles. 


37 











Conditions under which tests on SAC were conducted 




















*+G, accelerations umber | Rota- | Number 
Series ae of ene of 
of units /duration| quency |intervak, SUb- An J tests 
studies| min |per day h jects | oi. 
- 0.8 ’ 6 6 36 
1,2 60 2times; 106 12 6 6 3% 
1.6 4 6 24 
- 0.8 , 5 4 45 
1,2 40 3times; 6669 6 9 54 
1.6 | 6 9 54 




















The changes in parameters of the cardiovascular system were closely linked 
with the magnitude and duration of accelerations (Figure 1). Maximum 
changes were noted during the last minute of the plateau with the maximum 
tested acceleration of +1.6 Gz (Figure 2). Under these conditions, HR 
increased by 29-47%, as compared to the base level. The HR increment 

at +1.6 G, was 2-3 times greater than the changes in this parameter at 
+0.8 Gz (P<0.05). There was a mean 34-36% decrease in amplitude of 

ear lobe PPG by the end of the +1.6 G, plateau, which is 1.5-2 times 
greater than the change in this parameter at +0.8 Gz. It is important to 
note that there was a highly inverse correlation between dynamics of HR 
and ear lobe PPG amplitude at accelerations of 1.2 and 1.6 Gz (r = -0.721 
to 0.881). 


The amplitude of foot vessel PPG at 0.8 G, did not change, as compared to 
base data, and even increased in some subjects. At 1.6 Gz, we observed 

a decrease in amplitude of foot vessel PPG by a mean of 45% toward the 

end of the plateau. In some subjects, the foot PPG amplitude sometimes 
dropped down almost to the base line. This was associated with signifi- 
cant changes in configuration of the pulse wave (Figure 3), which were 
indicative of a significant increase in peripheral resistance to blood 
flow and appearance of a so-called phase of retrograde blood flow in 
arteries [5]. These changes in amplitude and configuration of foot vessel 
PPG sometimes coincided with sensations of increasing heaviness of the 
lower limbs. In one subject, we observed massive confluent hemorrhages 

in the region of the lower legs and feet after a marked decline in 
amplitude of foot vessel PPG (during ninth rotation in the mode of +1.6 Gz 
for 40 min, 3 times a day). 


Diastolic AP rose at all levels of accelerations and pulse AP dropped (see 


Figure 1). However, these changes were considerably less marked than the 
changes in parameters of regional circulation. 


38 














beats/ .ggc. 42Ge +462 Figure l. 


























man , : Dynamics of indices of the cardiovascular 
90+ Ay | system with exposure to accelerations of 
eat ta) ATT +0.8, 1.2 and 1.6 G, on SAC. Mean 
, ad fs ? ; id values for all rotations 
_— (ewe ‘= a) HR index 
0} x} , b) ear lobe PPG amplitude 
b NAL bo | c) lst toe PPG amplitude 
-T 4% Ni d) AP index: 1) systolic 
SOs iit ri Nu 2) diastolic 
% 3) pulse 
' | . 
o Here ami in Figure 4, the dotted line 
Or refers to the indices in the case of 
, rotation twice a day and solid line, 
te sepeeneeemmemmnenees three times a day 
a ae PN | ned 
80} 2 : 
60+ 43 | r : 
40, 5H ag 4 
20 oe www were 


01204080 01 204080 01 206060 Min 


Figure 2. 

r ri Changes in indices of the cardiovascular 
| : system with exposure to accelerations of 
: | +0.8, 1.2 and 1.6 G, on SAC. Mean data 
| fA comparing the base values to the last 
wey minute of the plateau (AZ) 
‘ a) HR index 

b,c) PPG amplitude, for ear lobe and foot 
=" | d) pulse AP 
| White columns, indices with rotation 


twice a day; striped columns, three 


26 Be times a day. Asterisks indicate P<0,.05 


7) 


os 








Q 





fen 
BPASoSSESRSoSSRS0OSEISES 


as compared to +0.8 Gz 








aé 6, 126, 


The observed distinctive features of changes in indices of the cardiovascu- 
lar system in the case of long-term exposure to accelerations on the SAC 

in the range of +0.8-1.6 Gz were apparently attributable to the marked 
nonuniformity of distribution of the accelerations over the body. While 
they were relatively nil at the level of the head, they reached maximum 
values in the region of the feet. This most probably led to a marked 
increase in filling of vessels of the lower extremities, as indicated by 


39 








the increase in amplitude of foot PPG in some subjects exposed to 0.8 Gz. 

As the magnitude and duration of accelerations increased, there was appa- 

rently substantial elevation of hydrostatic pressure in both the arterial 

and venous parts of the vascular system of the legs and feet, with appear- 
ance of signs of venous stasis in the lower limbs. 

















Figure 3. 
a b Dynamics of indices of the cardio- 
a + — ™ a vascular system with exposure of 
a agen Onan 6 ——_ oe _~—S—s subject S. to +1.6 G, accelerations 
NASA, UAA/AIVW—- _—s for 40 min on SAC. X's and dotted 
lines refer to “retrograde blood 
Nn Nn Nn Nn flow phase" (explained in the text) 
Cc . <i . , a) background 
- ow , b,c) plateau of +1.6 Gz, ist and 
AnaL AL p ; Y 7 40th min, respectively 
i j j | \ U | 
~/- , / d) lst min of aftereffect 
a ee Kf 1) 50 mm/s paper feed rate 
ees ee Oe A Nn 2,3) EKG in D and A leads of Neb 





calibration 1 mV = 1 cm 
4) PPG of first toe with base line 


The changes in the cardiovascular indices during rotation were also related 
to the frequency of exposure to accelerations. Analysis of HR dynamics 
as a function of sequential rotation number enabled us to demonstrate 
different tendencies of changes in this parameter in the second and third 
series of tests (Figure 4). In the second series, we observed two phases 
of change in this index with all tested modes: insignificant increase in 
HR from the first to third rotation, and relative stabilization between 
the fourth and sixth. Such dynamics of HR in the tests with rotation 
twice a day were probably attributable to signs of adaptation of the body 
to repeated exposure to accelerations at this frequency. In the third 
series of studies, we found a tendency toward progressive increase in HR 
from the first to ninth rotation. The mean HR between the sixth and ninth 
rotations differed reliably from the level at the first rotation (P<0.05). 
Also of interest is the fact that the mean HR with accelerations of 1.2 and 
1.6 Gz and overall values of HR in all modes of tested twice a day 

cycles differed with statistical reliability with the last (sixth) rota- 
tion (P<0.01) from the values of HR with the same number of rotations in 
analogous modes with a periodicity of three times a day. At the same 
time, when we compared HR after 1-5 rotations, we failed to demonstrate 
reliable differences between these series. The HR dynamics observed in 
the third series were attributable to cumulative effects of repeated 
rotation on the SAC with the three-phase cycle. 


Thus, in spite of the same values (+0.8, 1.2 and 1.6 Gz) and same total 
time of exposure to accelerations in 1 day (120 min) and during 3-day 


40 











beats?’ +126, | immersion (360 min), there was a sub- 

per min stantial difference in HR dynamics 

bad I with the two- and three-phase cycles. 

ce This indicates that it is not so 
much the magnitude of the gravita- 

%- tional impulse (product of magni- 
tude of acceleration and rotation 

time) as the interval between rota- 





tions that is the decisive factor 
for development of adaptation and 
cumulative effects in the case of 
periodic exposure to low-level 
accelerations on an SAC in the range 
of +0.8-1.6 Gz. 














or a5 790193 57390193 57% 

Rotations 
Figure 4. 

HR dynamics with exposure to +0.8, 

1.2 and 1.6 G, accelerations, and 

mean HR in all modes as a function 

of sequential rotation number on 

SAC. The asterisk refers to 

P<0.05 (as compared to first rotation) 


Thus, as a result of these studies, 
we demonstrated high resistance of 
the human body to prolonged head- 
pelvis accelerations with a high 
gravitation gradient over the body 
in the range of 0.8-1.6 G,. Pre- 
dominant changes in regional circu- 
lation in the lower extremities was 
the typical distinction of reac- 
tions of the cardiovascular system to low-level accelerations with a high 
gravitation gradient. The changes in cardiovascular indices with periodic 
exposure to accelerations on the SAC were closely related to the magnitude, 
duration and frequency of exposure, as well as individual distinctions of 
regulatory mechanisms of the cardiovascular system. 


The obtained data pertaining to substantial differences in extent of change 
in indices of the cardiovascular system with exposure to low levels of +6, 
accelerations om the SAC, differing by tenths of a G, can be used to 

find optimum modes of rotation for an onboard centrifuge. 


BIBLIOGRAPHY 
l. White, W. J. in "Symposium on the Role of the Vestibular Organs in 
the Exploration of Space, lst, Proceedings," Washington, 1965, pp 209- 
213. 


2. Piemme, T. E.; Hyde, A. S.; McCally, M.; et al. AEROSPACE MED., Vol 3/7, 
1966, pp 16-22. 


3. Nyberg, J. W.; Grimes, R. H.; and White, W. J. Ibid, pp 665-668. 


41 








4. Shul'zhenko, Ye. B., and Vil'-Vil'yams, I. F. KOSMICHESKAYA BIOL. 
[Space Biology], No 2, 1976, pp 82-84. 


5. Folkow, B., and Neil, E. "Circulation," Moscow, 1976. 











42 








UDC: 612.11/.12.014.46:546.262.31 


REACTION OF HUMAN BLOOD TO CHRONIC EXPOSURE TO LOW DOSES OF CARBON MONOXIDE 
IN A CONFINED ENVIRONMENT 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 31-35 


[Article by V. V. Zhuravlev, Z. M. Karelina, Ye. I. Nikitin and V. P. 
Savina, submitted 28 Feb 78] 


{English abstract from source] 


Morpholcgy, biochemistry and acid—base equilibrium of blood of test subjects 
during their chronic exposure to low doses of carbon monoxide in an enclosed envi- 
ronment have been studied. 


[Text] Carbon monoxide is one of the components that always pollutes the 
air environment of sealed compartments, in particular spacecraft. Diverse 
equipment, polymers and, finally, man himself may be the source of dis- 
charge of carbon monoxide [1l, 2]. 


Most authors who have studied the toxic effect of carbon monoxide on 
animais and under industrial conditions on man detected specific changes 
in morphology and biochemistry of blood [3-9]. However, these works 
dealt mainly with the study of brief exposure to high concentrations of 
carbon monoxide. 


In the first studies of the chronic effect of low concentrations of carbon 
monoxide [10, 11], functional disturbances of the animal nervous system 
were investigated. Subsequently, a number of authors [12-14] confirmed 
the possibility of chronic carbon monoxide poisoning with exposure to 
doses on the level of the maximum permissible concentrations. 


Our objective here was to study the effect of long-term exposure to carbon 
monoxide in concentrations of 10-20 mg/m’, against the background of the 
aggregate of all factors inherent in staying in a restricted, sealed 
compartment. 


43 





Our objectives also included the study of the effects of carbon monoxide 
in the presence of worse microclimate (simulation of accident [emergency] 
situations). 


Methods 


These studies involved the use of a 24 m* sealed chamber in four tests 
lasting 30 to 90 days. Four volunteer subjects, ranging in age from 23 to 
36 years, participated in each study. In each of the last two tests, 

we simulated two “accident situations” with more difficult living condi- 
tions for 24 h (Table 1). For the analyses, we used blood taken from 

the finger. Blood was collected on a fasting stomach under standard 
conditions, on the 2d, 7th, 12th, 18th, 24th and 30th days, as well as 

at the end of the "accident situations." Carboxyhemoglobin content was 
assayed using a modified spectrophotometric method and catalase activity 
by the method of Bakh and Zubkova [15]. We also monitored the concentra- 
tion of nonhemoglobin iron in blood serum [16]. Erythrocytes and hemo- 
globin were assayed by photoelectrocolorimetry using an FEK-M instrument. 
Blood gases and acid-base balance (ABB) were examined by a micromethod 
according to Siggaard-Andersen using an Astrup instrument. Tests that 
were conducted in the same chamber without carbon monoxide in inhaled 

air served as a control. 


Table 1. Microclimate during tests on ordinary days (A) and days of 
“accident situations" (B) 





A R 
humé! day concentratim 


of ; : dit 
ws - type” Oy. %s (CO. %! °C Y, 











of study, concent 
days co, mg/m* 


2 
al 
pw 
al 
ee 
° 
el 
— 





Oy. % |CO,. ‘| °C 








30 | 19.2—21.1 
30 «| 14,.2—16.2 |19,0—10 ,42—/21 .0—'46—70 
—2 4|—0 .67|—22.6) 
30 | 14,6—16,8 13. | 16.2} 20.2] 2.4 | 32,0] 86,7 
90 2% | 15.91 19.4) 3,0 | 32,3 | 87,3 
9 5—11.0 © | 46.2) 21.1! 3.0 | 34.8] 91,0 
32 | 46.5) 20.8! 3.1 | 35,0] 90.0 



































Results and Discussion 


The subjects’ blood pH was in the range of 7.36-7.41, carbon dioxide 
tension (PaCOz2) ranged from 35 to 43 mm Hg and buffer bases (BB) ranged 
from 47.5 to 54.7 meq/% in the case of 30-day exposure to carbon monoxide 
in a concentration of 20 mg/m°* with a comfortable microclimate in the 
pressure chamber. Standard bicarbonates (SB) and buffer base shift 

(BE [base excess]), which characterize the extent of metabolic changes, 
were in the normal range (from +1.5 to -1.5 meq/2). At the end of the 
test, three subjects presented elevation of PaCO, to 46 mm Hg, versus 

the background value of 41 mm Hg (Table 2). 


44 











ee « 
——— ee 
eon-VoOow 

eer. * 





r7oc-4“°o 





se ff © © 


~-rEoo 





hat 





seen oe @ 











0,9 
,. 





23,2 








41,48 





eee * 





pil 


7,378 


Changes in blood parameters in minimum-maximum tests 


se@2d8s8 88 


6 
35 
557 





i id 


>. & | @ # 





Table 2. 











"Carbon monoxide content in air of pressure chamber during “accident situation." 








There were no substantial changes at 
the start of the study in blood mor- 
phology. We consistently demonstrated 
elevation by a mean of 14% of back- 
ground value in level of hemoglobin 
starting on the 18th day. Carboxy- 
hemoglobin content was high throughout 
the test period, and it constituted a 
mean of 11.3%. Of the other biochemical 
parameters studied, we should mention 
the increase in nonhemoglobin iron in 
the second half of the study, from 127 
to 149 ez, as well as a reliable 
(P<0.05) decline of catalase index from 
4.46 to 3.79. 


In the second study, involving exposure 
to carbon monoxide in a concentration 
of 15 mg/m’, we found an 11.4% elevation 
of PaCO2 on the 12th day, as compared 
to the background, with concurrent 
elevation of PaO, from 112 to 118 mm Hg. 
During this period, one of the subjects 
presented acidotic changes of a respi- 
ratory nature, with unsatisfactory 
renal compensation. By the end of the 
study, PaCO», was elevated in all sub- 
jects, reaching 47-54 mm Hg in some 
cases, while pH dropped to 7.35, which 
is typical of uncompensated respiratory 
acidosis. There was negligible change 
in erythrocyte count and blood hemo- 
globin content. Throughout the study, 
COHb constituted a mean of 10.5%, non- 
hemoglobin iron content was on the 
level of 124 yg% and catalase activity 
held at 4.12. 


There was elevation of PaCO2 on the 

first day of the third study, as a 
result of which some subjects presented 
acidotic changes of a respiratory nature. 
On some days, PaCO: reached 47-50 mm Hg 
at pH 7.35. Blood PaO, dropped to 

12-15 mm Hg below the initial level. 


When the habitat conditions were made 


more difficult in this study, we 
found normalization of acidotic changes 


45 





as manifested by a drop of PaCO2 to 44.4 mm Hg at pH 7.37. As a result of 
increased ventilation, Pa0z2 rose to a mean of 125 mm Hg. 


During this study, blood morphology underwent insignificant change, but 
erythrocyte count dropped by 4 mean of 12% of the base level and hemoglobin 
decreased from 15.1 to 13.9 g% on the 13th and 25th days. The concentra- 
tion of carboxyhemoglobin increased fron 10.5 to 14.7%, while nonhemoglobin 
iron increased on the 25th day from 122 to 134 gt under the more difficult 
conditions. The catalase index remained virtually unchanged in this study. 


Studies of ABB in the first half of the fourth study consistently revealed 
changes in all subjects inherent in respiratory acidosis varying in degree 
of compensation. On some days PaCO2 reached 55 mm Hg. In some cases, 
metabolic disturbances of ABB were added (BE = 4.0 meq/L) to the signs of 
respiratory acidosis. 


As a result of exposure to the more difficult habitat conditions, on the 

33d day the subjects presented elevation of PaCO2 to 59.0-62.0 mm Hg. The 
active blood reaction dropped to 7.33. From the 64th day on, there was 
normalization of ABB; however, PaCO2 remained 10% above the background level. 


The subjects’ blood presented an increase in erythrocyte count, from 4.2 
million to 4.41 million, and in hemoglobin, from 15.3 to 16.5 g%, from 
the first davs of the study. 


Starting on the 49th day, erythrocyte count and hemoglobin content of peri- 
pheral blood gradually decreased, constituting 3.86 million and 14.6 g%, 
respectively, versus base levels of 4.27 million and 15.4 g%. The COHb 
concentration held at 4.3% and nonhemoglobin iron at 137 gr throughout 
the period of the study. During the period of worse microclimate, these 
parameters increased to 17.7% and 161 ug%, respectively. The catalase 
index changed only during the second "accident situation,” when it dropped 
from 3.27 to 2.81. 


When analyzing the obtained results, one should proceed not only from the 
fact that the selected concentrations of carbon monoxide exerted an 
influence, but that the entire aggregate of conditions inherent in sealed 
environments had an effect on the subjects. Along with specific changes 
in amount of carboxyhemoglobin and nonhemoglobin iron, and changes in 
activity of catalase indicative of varying degrees of carbon monoxide 
poisoning, we demonstrated changes in acid-base status of the human body. 
It should be noted that, with chronic exposure to carbon monoxide in 
concentrations of 10-20 mg/m’, we demonstrated a difference only in 
severity of ABB disturbances, which were characterized mainly by an 
increase in carbon dioxide tension in blood and moderate decline of its 
pH. As a rule, elevation of PaCO2 was associated with some elevation 

of blood PaOe which, in turn, was the result of compensatory increase in 
pulmonary ventilation. However, the respiratory compensation did not 
provide for an appropriate decline of PaCO;. On this basis, it can be 


46 











assumed that this phenomenon is related to diminished activity of carbonic 
anhydrase which is involved in decomposition of carbonic acid and elimina- 
tion of carbon dioxide [17-19]. Nor can we rule out the possibility of 
elevation of the threshold of excitability of the respiratory center 

under the influence of the tested concentrations of carbon monoxide. In 
favor of this hypothesis is also the decline of PaCOz2 and normalization 
of acidotic symptoms on the 13th and 25th days of the third study, when 
the concentration of carbon monoxide in the chamber was increased, air 
temperature was raised and humidity increased, which led to significant 
increase in pulmonary ventilation. We failed to demonstrate such an 
effect in the fourth study, where we increased the carbon monoxide level 
to 46 mg/m? » along with elevation of temperature and increase in carbonic 
acid in the chamber. Evidently, this concentration of carbon monoxide 
induced even greater changes in regulation of respiration. 


In the 90-day study, where the subjects. were continuously exposed to carbon 
monoxide in a concentration of 10 ng/m* » the previously observed changes in 
ABB, erythrocyte and nonhemoglobin iron content leveled off after the 
subjects had spent 41 days in the tested atmosphere. Hence, the signs 

of carbon monoxide poisoning demonstrated at the start of the study 
leveled off as a result of development of adaptive reactions, and this 
was aided by creating comfortable conditions in the chamber. However, it 
must be borne in mind that, with increase in duration of the stay in the 
chamber and development of asthenization, there was a decrease in reacti- 
vity of the body, and the time could come when there would again be 
manifestation of carbon monoxide poisoning. We cannot explain at the 
present time the fact that greater changes are demonstrable with exposure 
to carbon monoxide in a concentration of i5 ng/m* than 20 mg/m° » since 
there were too few subjects involved in our studies. 


Thus, studies of the effect of carbon monoxide in concentrations of 

10-20 mg/m°* under ordinary and difficult living conditions revealed that 
there were ABB disturbances of an acidotic nature, as well as a change in 
blood levels of carboxyhemoglobin, nonhemoglobin iron and in catalase 
activity. The toxicity of the tested concentrations of carbon monoxide 
depends on the entire set of factors inherent in the environment of a 
sealed chamber. 


BIBLIOGRAPHY 


1. Sjostrand, T. NORD. MED., Vol 43, 1950, p 211. 


2. Savina, V. P.; Sokolov, N. L.; amd Nikitin, Ye. I. KOSMICHESKAYA BIOL. 
[Space Biology], No 6, 1974, p 62. 


3. Kreuzer, F., and Roughton, F. HELV. PHYSIOL. PHARMACOL. ACTA, Vol 12, 
1954, p 78. 


47 











Dvoryaninova, N. K. in “Voprosy gigiyeny tr profpatologii i 
promyshiennoy toksikologii” [Probiems of Ind rial Hygiene, Occupa- 
tional Pathology and Industrial Toxicology], Sverdlovsk, Pt 2, 1958, 
p 222. 


Stolyarchuk, N. K. in “Promyshlennaya toksikologiya" [Industrial 
Toxicology], Moscow, 1960, p 283. 


Kol *kovskiy, P., and Raycheva, V. GIG. TRUDA [Industrial Hygiene], 
No 11, 1962, p 35. 


Zatsepilin, a. G. in “Voprosy professional'noy patologii v osnovnykh 
otraslyakh promyshlennosti Luganskoy oblasti™ [Problems of Occupational 
Pathology in the Main Branches of Industry in Luganskaya Oblast], 
Lugansk, 1965, p 23. 


Zhgutov, I. I., and Khalepa, B. F. in "Dnepropetrovskiy med. in-t. 
Nauch. sessiya. 28-ya. Materialy" [Proceedings of 28th Scientific 
Session of Dnepropetrovsk Medical Institute], Dnepropetrovsk, 1965, 
p 72. 


Tiunov, L. A., and Kustov, V. V. "Toxicology of Carbon Monoxide," 
Leningrad, 1969. 


Gorsheleva, L. S. FARMAKOL. I TOKSIKOL. [Pharmacology and Toxicology], 
No 5, 1944, p 47. 


Frolov, Yu. P. "Higher Nervous Activity in the Presence of Toxicosis," 
Moscow, 1944, 


Gadaskina, I. D., et al. GIG. TRUDA, No 11, 1961, p 13. 
Pecora, L., et al. FOLIA MED. (Naples), Vol 41, 1958, p 97. 


Kustov, V. V.; Tiunov, L. A.; and Vasil'yev, G. A. GIG. TRUDA, No 6, 
1963, p 53. 


Pushkina, N. N. “Biochemical Methods of Investigation," Moscow, 
1963, pp 195, 309. 


Kassirskiy, I. A. (editor) "Manual of Functional Diagnostics," 
Moscow, 197C, p 378. 


Korsun', A. Ya. quoted by L. A. Tiunov and V. V. Kustov. 


Kremneva, S. A. in "“Voprosy promyshlennoy toksikologii" [Problems 
of Industrial Toxicology], Moscow, 1960, p 104. 


Guarino, A.; Biondi, S.; Bocculatte, F.; et al. FOLIA MED. (Naples), 
Vol 42, 1959, p 376. 


48 





UDC: 616-001.12-02:612.014.464 


PROBABILITY OF ALTITUDE DECOMPRESSION DISORDERS WHEN BREATHING OXYGEN 
CONTAINING HUMAN WASTE GASES 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 36-39 


[Article by A. V. Sedov, A. N. Mazin and N. A. Surovtsev, submitted 
ll Jan 78] 


[English abstract from source] 


Probability of altitude decompression disease in a hypobaric oxygen environment 
containing gaseous human wastes has been explored. The development of the disease 
does not depend on the presence of wastes in the environment. Its frequency increases 
with exercises. The decrease of the barometric pressure to 308 mm Hg causes decompres- 
sion disease only in the test sudjects having traumatized limbs. The frequency o the 
disease during further decrease in the pressure down to 198 mm Hg increases substan- 
tially 


[Text] There has been insufficient study of the problem of occurrence 
of altitude decompression disorders (ADD) in man as related to the 
chemical composition of an artificial gas atmosphere (AGA). We know of 
only a few studies in this field [1-4]. It was reported in them that 

an increase in carbon dioxide in oxygen used for breathing is involved 

in development of ADD. However, the oxygen used for breathing in space 
suits with regeneration types of life support systems usually contains 
not only carbon dioxide, but other human waste. According to data in the 
literature [5-8], such waste products as carbon monoxide, aliphatic and 
aromatic hydrocarbons, amines and acetone are of the greatest toxicological 
and hygienic significance in polluting the AGA. For this reason, it is 
deemed expedient to pursue studies in order to determine the correlation 
between incidence of ADD and degree of rarefaction of the atmosphere and 
levels in oxygen used for breathing of the above-mentioned human waste. 
Such information is needed to obtain base data to be used for development 
of measures to prevent ADD. 


49 











Methods 


To solve this problem, we conducted studies involving 44 subjects ranging 

in age from 20 to 45 years. In all, we conducted 669 tests at "altitudes" 
of 7000 and 10,000 m. The "climb" to 7000 m was made without prebreathing. 
Prior to ascending to 10,000 m, the subjects breathed pure oxygen for 1 h. 
They reached the “altitude” of 7000 m in 1.5-2 min and 10,000 m in 2-3 min. 


During the tests, the subjects breathed either pure oxygen (background 
data), or oxygen containing human waste: carbon monoxide (concentration of 
10-300 mg/m*), methane (150-400 mg/m’), acetone (50-200 mg/m’), phenol 
(3-9 mg/m*) and dimethylamine (DMA, 0.5-1 mg/m*). We also tested the 
effects of various combinations of oxygen and waste products: carbon 
monoxide, methane and phenol; carbon monoxide and DMA. We selected the 
concentrations of waste products on the basis of possible level of 
accumulation in sealed environments [9]. 


During the tests, the subjects either rested, or performed moderate 
physical work involving 5-6.5 kcal/min expenditure of energy. Upon reach- 
ing the indicated “altitude” and after recording vital physiological 
parameters, the subjects immediately began the physical work. This 

was done in cycles, on a physical load stand, where the subjects lifted 

a weight with the hands and feet simultaneously. The exercise cycles 
lasted 49 min with 20-min intervals between them. In all, the subjects 
perfcrmed six work cycles in the 6 h they spent at a given "altitude." 
Air temperature in the pressure chamber was 18-27°C and relative humidity 
was 40-60%. The subjects wore either cotton underwear or pressure suits. 
They spent 6 h at the indicated “altitude.” 


Onset of ADD was diagnosed according to the subjects’ subjective reports. 
In addition, their general condition was evaluated according to the 


data from continuous medical monitoring. 


Upon appearance of th first signs of ADD, the subjects were rapidly 


"brought down" hospit.'ized for 24 h, during which time they were 
submitcec | -cuprehensive clinical examination. 
Res ana Discussiocu 


The Tabl. shows the distribution of ADD as related to experimental conditions. 


This table shows that ADD occurred in 0.5% of the cases (3 out of 585 
tests) when the subjects were lifted to an "altitude" of 700 m. These 
three cases were referable to three different subjects. For this reason, 
the percentage of ADD calculated in relation to subjects involved in 

this series of tests (44) constituted 6.8%. The observed cases of ADD 
were referable to the most frequently encoutnered bone and joint form 
(bends). After the “descent,” the pains in the joints and muscles dis- 
appeared without a trace. The cases of ADD detected during the tests can 





50 








be classifed, according to the classification of Gray [10] and several 
other researchers, as the mild stage, which is characterized by mild 
pain occurring mainly upon moving. Clinical examination of subjects 
with ADD failed to demonstrate deviations from normal with reference to 
functional systems. In two of the three cases of ADD occurring at the 
indicated barometric pressure, the subjects breathed pure oxygen and 

in the other, a gas mixture with methane in a concentration of 400 mg/m’. 
Analysis of the cases of ADD failed to demonstrate any influence on the 
part of human waste gases contained in oxygen in the above concentrations 
on the probability of ADD. Decompression disorders were found in two 
subjects who performed exercises and one who remained at rest. However, 
when compared to the number of tests conducted under the same conditions, 
these cases did not enable us to demonstrate an effect of exercise on 

the incidence of ADD at a barometric pressure of 308 mm Hg. 


Probability of ADD in subjects at barometric pressure of 308 and 




















198 mm Hg 
Temp, |Physical 
earo~ AGA a activity, 
Bn tan - kcal/min 
, 
anes mm Hq o 6 
“| &!% = + 

S/S) Gl 8 2598 - Sl ele 

a < +> + + at} i+ | | A rf 

=> | =| ol Si Si oi oi sporAct sia) =] « 

Number of testa 585 | 84 [|334/151/ 84 | 26) 43/53! 41 | 26)448/212) 84 | 585 

Cases of ADD 3 6 5} 3) ft! OF} OF O 0 0; 5) 4) 2 7 

| 












































*Prebreathing for 1 h. 


A scrutiny of the history of these three subjects revealed the following: 
subject R. had had a dystrophic process in the left knee joint in the 
past; P-v had sustained trauma of the right ankle, while I-ko, who had 
skied, played soccer and hockey for 15 years, had sustained numerous 
traumas and contusions to the major joints. In all three cases, altitude 
decumpression pain was localized expressly in the regions of traumatized 
knee and ankle joints. 


The results of the tests conducted at an “altitude” of 10,000 m revealed 
that, in spite of l-h prebreathing with pure oxygen, the incidence of ADD 
increased drastically with decline of barometric pressure and their 
severity increased. The incidence of ADD among subjects exposed to this 
barometric pressure constituted 7.1% (6 cases out of 84), or 25% in 
relation to number of subjects (4 out of 16 subjects participating in this 
series of studies). At this pressure, ADD was manifested in a more marked 











form and, in several cases, occurred in the form of severe muscle and joint 
pain. Most of the ADD cases demonstrated in this series of tests (4 cases) 
could be classified as the first stage of decompression disorders, accord- 
ing to the classification of Gray [10]. However, according to the same 
classification, two cases of ADD should be identified as the second 

stage, which is characterized by tolerable but gradually increasing pain. 
This pain, as in the preceding series of tests, disappeared without a 
trace after the subjects "descended" from the high "altitude." We failed 
to demonstrate a single case of third stage ADD in either series of tests. 


In three of the six cases of ADD that occurred at 10,000 m, the subjects 
breathed pure oxygen and in the three others, oxygen containing carbon 
monoxide in a concentration of 15 mg/m°. Thus, it is not deemed possible 
to make a judgment in this series either with respect to the effect 

of gas mixtures containing human waste on probability of occurrence of ADD. 
We were impressed by the fact that ADD occurred during performance of 
physical work in five cases and at rest in one. This confirms a fact that 
is known from the literature [11], that physical exercise is instrumental 
in occurrence of ADD. As in the preceding series, we failed to demonstrate 
any pattern of change in probability of ADD as a function of ambient 
temperature. 


The six cases of ADD were distributed as follows: at an “altitude” of 

10,000 m, ADD occurred 3 times in the same subject (D-ko), and the 

other 3 cases were referable to others (Ts-ch, G-v and P-n). The his- 
tories revealed that subject D-ko had had a femoral fracture, while G-v 

had suffered a spiral fracture of theieg; however, the other two sub- 
jects (P-n and Ts-ch) had not sustained any trauma in the past. Evidently, 
as was the case at an “altitude” of 7000 m, prior history plays an important 
role in onset of ADD at 10,000 m (4 out of 6 cases). At the same time, 
analysis of incidence of ADD as a function of a specific waste product and 
its concentration in the AGA reveaeld that these factors do not affect 

the probability of occurrence of this disease. Thus, there were 5 cases 

of ADD out of 334 when breathing pure oxygen and 4 out of 335 when breathing 
gas mixtures. 


Thus, analysis of the obtained data enables us to conclude, with some degree 
of probability, that the waste products studied cannot cause development 

of ADD at “altitudes"™ of 7000 and 10,000 m in the concentrations that may 

be encountered in the artificial gas environment of sealed compartments. 

At these “altitudes,” ADD occured both during performance of heavy physical 
labor and at rest. Analysis of the obtained data warrants the conclusion 
that it is imperative to conduct occupational screening of candidates for 
work at low barometric pressure with due consideration of their prior 
medical history. 





52 











10. 


ll. 


BIBLIOGRAPHY 


Genin, A. M. VOYEN.-MED. ZH. [Military Medical Journal], No 8, 1948, 
pp 48-51. 


Gramenitskiy, P. M. "Conditions and Mechanism of Development of 
Decompression Disorders," doctoral dissertation, Leningrad, 1967. 


Zagryadskiy, V. P.; Sidorov, 0. Yu.; and Sulimo-Samuyllo, Z. K. in 
"Problemy kosmicheskoy meditsiny" [Problems of Space Medicine], Moscow, 
1966, pp 175-176. 


Behnke, A. R. MEDICINE (Baltimore), Vol 24, 1945, pp 381-402. 


Gorodinskiy, S. M.; Sedov, A. V.; Mazin, A. N.; et al. KOSMICHESKAYA 
BIOL. [Space Biology], No 4, 1968, pp 72-76. 


Kustov, V. V., and Tiunov, L. A. "Toxicology of Biological Waste 
Products and Significance Thereof in Formation of the Artificial 
Atmosphere of Sealed Compartments," Moscow, 1969. 


Nefedov, Yu. G.; Savina, V. P.; Sokolov, N. L.; et al. KOSMICHESKAYA 
BIOL., No 5, 1969, pp 71-77. 


Uands, R. K. in "Osnovy kosmicheskoy biologii i meditsiny" [Funda- 
mentals of Space Biology and Medicine], Vol 2, Bk 1, 1975, pp 74-104. 


Sedov, A. V. in "Problemy individual'noy zashchity cheloveka" 
{Problems of Personnel Protection], Moscow, Pt 2, 1974, pp 3-37. 


Gray, J. S. in "Decompression Sickness," ed. by J. F. Fulton, 
Philadelphia, 1951, pp 182-191. 


Malkin, ¥. B. in "Osnovy kosmicheskoy biologii i meditsiny," Moscow, 
Vol 2, Bx 1, 1975, pp 11-73. 


53 








UDC: 612.127,2-06:612,273.1 
EFFECT OF HYPEROXIA ON OXYGEN TRANSPORT PROPERTIES OF BLOOD 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 39-42 


[Article by L. A. Ivanov and N. D. Chebotarev, submitted 7 Aug 78] 


[English abstract from source] 


In 9 normal test subjects, aged 19—32, pO,, pCO, and pH of arterial and venous 
blood were measured. The curve of oxyhemoglobin dissociation during 20 min inhala- 
tion of a 95 % O, containing mixture was analyzed. The studies demonstrate that 
during hyperoxia there is a shift to the left of the dissociation curve in native blood 
and standard curve (i. e. normalized to pH 7.4). This shift of the curve of oxyhemoglo- 
bin dissociation indicating an increase in hemoglobin affinity for oxygen seems to be 
one of the factors responsible for an increase in the pO, arteriovenous difference and 
a much lower increment of venous pO, than that of arterial pO,. 


[Text] The wide use in aviation and space medicine of oxygen at normal and 
high pressure, on the one hand, and side-effects with the use thereof, on 
the other [1-4], make it necessary to conduct an in-depth study of the 
effect of this gas on the body. Yet, many aspects of the functional 

state of organs and systems in the presence of hyperoxia have still not 
been investigated sufficiently. This applies, in particular, to the 
respiratory function of blood, which plays a first and foremost role in 
providing for oxygen homeostasis in the body. 


Our objective here was to study oxygen transport function of blood in 
essentially healthy individuals, in the presence of hyperoxia. 


Methods 
We studied 9 healthy individuals ranging in age from 19 to 32 years. 


They breathed a gas mixture containing 95% oxygen and 5% nitrogen from 
the closed system of an SG-1M spirograph for 20 min. Oxygen content of 
the working cylinder of the spirograph was monitored with an MMG-7 oxy- 
gen analyzer, which was connected to the spirograph at the point of 
attachment of the gas analyzer for determination of residual lung volume. 


54 











Before the test and in the 19th-20th min thereof, we took arterial (from 
brachial artery) and venous (from ulnar vein) blood to measure oxygen 
(p02) and carbon dioxide tension (pC02), pH, as well as venous blood to plot 
the curve of oxyhemPglobin dissociation. Blood was taken by puncturing 
vessels into a dry sterile syringe. The blood intended for measurement 
of gas tension and pH was transferred into a cooled test tube with 1-2 
drops of heparin solution (1:5 dilution) under vaseline oil, after which 
the tube was put on ice and in the refrigerator. The tests were made 

no later than 2 h after taking blood. Blood was taken from the test 

tube with a syringe with a long needle, and immediately transferred to 

the measuring dishes [pits]. The method of taking the blood and trans- 
ferring it into the measuring dish precluded its contact with atmospheric 
air; the pH was determined electrochemically and p02 polarographically 

by menas of a Clark electrode. The measurements were made with a micro- 
Astrup instrument (Denmark), type PHM-71. An ABC70 (Denmark) computer was 
used to calculate pCO2 on the basis of pH value. 


We analyzed the curve of oxyhemoglobin dissociation obtained on a DCA-1 
instrument (Denmark). In order to determine the oxygen-binding proper- 
ties of blood, the instructions for use of this apparatus indicate 

that one should determine the half-saturation points (Pso), i.e., the 
p02 levels at which hemoglobin is 50% oxygenated. This parameter is 
known as the "discharge tension" [5] and reflects the blood's capacity 
to give off oxygen to tissues. An increase in Pso signifies a shift of 
the curve to the right, indicative of decreased affinity of hemoglobin 
for oxygen, while a decrease in Pso indicates a shift to the left, which 
reflects increased affinity of hemoglobin for oxygen. 


Since the DCA apparatus produces an oxyhemoglobin dissociation curve 

that is typical for a given batch of blood with its inherent pH, determina- 
tion of Ps9 at standard pH is made in accordance with the instructions 

for use of the apparatus. 


However, determination of Ps»9 is not enough to evaluate the oxygen trans- 
port function of hemoglobin. Indeed, evaluation of level of oxygenation 
of hemoglobin at the most diverse levels of p02 appears to be substantial. 
For this reason, we performed the procedure, which is described above 

for determination of Pso, to find the p02 levels corresponding to 10, 20, 
30, 40, 60, 70, 80, 90 and 100% oxygenation of hemoglobin. This enabled 
us to plot the standard curve of dissociation of oxyhemoglobin at a stable 
pH (7.4), in addition to the curve of oxyhemoglobin dissociation inherent 
in the actual conditions of a given blood sample with its inherent pH and 
pCO, levels. As a result, it was possible to make a differentiation, 

by neutralizing the blood pH changes, between the significance of intra- 
erythrocytic factors and actual changes in hemoglobin, on the one hand, 
and extraerythrocytic factors in the dynamics of oxygen-binding properties 
of hyperoxic blood. 


55 








Results and Discussion 


As shown by our studies, p02 levels corresponding to all analyzed levels 
of hemoglobin oxygenation dropped in unadulterated blood in the oxygen 
test. The drop of p02 was reliable within the range of Pso-Peo. This 

decline reflects an increase in affinity of blood for oxygen and a shift 


to the left of the curve of dissociation of oxyhemoglobin in the presence 
of hypoxia (see Figure). 






















































































100 , - Curve of dissociation of oxyhemo- 
a | 
9% , globin in native blood in the 
& 8 ’ base state (solid line) and with 
«, 7 , + hyperoxia (dash line) 
oO @ 
Ce 
.3 = 
c W j 
o> M7 rt 
x of | 


10 20 30 © 50 60 70 80 9 100 
J0r,mm Hg 


Studies of the standardized curve of dissociation of oxyhemoglobin revealed 
that the reliable shift of the curve to the left under hyperoxic conditions 
was retained. The p02 corresponding to all tested levels of oxygenation 
was lower than in the base state, and the decline of p02 was reliable in 
the range of P2o-Pso (see Table 1). 


According to the data listed in Table 2, in addition to the distinct 
increase in arterial oxygen tension (p,02) in the presence of hyperoxia, 
there was a significant increasein arteriovenous difference forp02, as a 
result of which the increase in oxygen tension of venous blood (p,,02) was 
significantly less marked than the increase in pgO2. Under hyperoxic 
conditions there was virtually no change in levels of pCO2 in arterial and 
venous blood, as well as arteriovenous difference forpC02. Accordingly, 
no reliable changes were demonstrated in pH of arterial and venous blood. 


Hyperoxia led to a distinct increase in affinity of hemoglobin for oxygen 
in the tested individuals. With reference to the mechanism of this pheno- 
menon, we must note the following: In the first place, blood pH and pC02, 
i.e., the most important extraerythrocytic factors affecting affinity of 
hemoglobin for oxygen, underwent very negligible change during the oxygen 
test (see Table 2). In turn, the lack of changes in blood pCO2 and pH is 
attributable to the virtually stable level of ventilation [6-8] and gas 


56 











exchange [3, 9] under hyperoxic conditions. In the second place, with 
inhalation of oxygen the shift to the left of the standard curve of oxy- 
hemoglobin dissociation persisted, i.e., the curve scaled to standard pH. 
Therefore, it can be stated that the increase in affinity of hemoglobin for 


oxygen in the presence of hyperoxia is attributable to intraerythrocytic 
mechanisms. 


Table 1. Magnitude of shift of indices of curve of oxyhemoglobin disso- 


ciation (mm Hg) in the presence of hyperoxia, as compared to 
the base level 

















a = 
ar O41 6 
ay 8 OWA 
x Uv oes Go rw 
Y e) AIiDVsvoa 
s oo elc P “44 
& |2353| 3583 . 
Opveclnvuoan 
Pre —).4 —0.5 
Pro —1,0 | —1,06 
P55 —-] 3 —!| 36" 
Py —1.4 —1 24° 
Pro —1.9 —1 ,69* 
Peo —2.0* | —1,81* 
Ps —2,.3* | —2,2° 
Po —2,4* —2 1* 
Pos —1.4 | —1,51 
Pico —3,1 —3,1 
* P<0,05. 


Table 2. Indices of gas composition (Mtm) and pH of arterial and venous 
blood in the presence of hyperoxia 











Base i 
Index level Hyperoxia 
A . 
3 te - 9534-4 ,02 252+-16,09° 
pH 7 ,38+-0,06 | 7,3832-9,152 
pCO,, mm H 36,1+1,02 | 35,3-41,93 
Venous bl : 
POs, mn Hg 33,2+1,1 40 5+1, 24° 
DH 7,33+0,05 | 7,3462-0,041 
pCO2, mm Hg 43.5+1,2 44 51 58 
LEE e ee ee He 62,347.18 | 212,9-+16,4° 
Arteriovenous 
mig 7,741.12 9,23-+1,63 








*P<0,01 as compared to base level. 


57 





What then is the significance of the shift to the left of the curve of 
dissociation of oxyhemoglobin, which was demonstrated with inhalation of 


oxygen? 


As shown by the studies, there was an increase in arteriovenous p02 differ- 
ence when breathing oxygen (see Table 2). We cannot attribute the increase 
in arteriovenous difference for p02 exclusively to slowing of blood flow, 
which is inherent in hyperoxia [10, 11], since the dynamics of arterio- 
venous difference for pCOz2 were insignificant (see Table 2). The higher 
point in the artery, at which delivery of oxygen to tissues begins, on the 
curve of oxyhemoglobin dissociation in the presence of hyperoxia is also 
important, and as a result the discharge of oxygen by hemoglobin is associ- 
ated with increase in arteriovenous difference for pOz. In the light of 
these data, the greater arteriovenous difference for p02 in the presence of 
hyperoxia could also be attributed to affinity of hemoglobin for oxygen, 

as a result of which delivery of oxygen by blood to tiss:*: is associated 
with significant decline of p02 in blood plasma. 


It could be assumed that increased aifinity of hemoglobin for oxygen should 
lead to increased association of hemoglobin with oxygen in the lungs. How- 
ever, expressly in the range of high levels of hemoglobin oxygenation 
(starting at 90%), there was unreliable increase in affinity of hemoglobin 
for oxygen. Moreover, regulation of rate of association of hemoglobin 
with oxygen is less significant than regulation of rate of dissociation of 
oxyhemoglobin. Indeed, while the rate of delivery of oxygen by blood is 
not high (50% oxygen given off by erythrocytes in 0.75-0.9 s) and affinity 
of hemoglobin for oxygen has an appreciable effect on it, association of 
oxygen and hemoglobin occurs 10 times faster, and 50% oxygenation of erythro- 
cytes requires 0.08-0.09 s [12]. This rate is quite adequate for normal 
oxygenation of erythrocytes, and change therein within a certain range 
would not affect the process. 


Thus, in the presence of hyperoxia there is an increase in affinity of hemo- 
globin for oxygen, which is manifested by a shift to the left of the curve 
of dissociation of oxyhemoglobin. The increase in affinity of hemoglobin 
for oxygen is one of the causes of the distinct increase in arteriovenous 
difference for pQ2 and significantly lower increment of p02 in venous 

blood than the increment of p,02 during the oxygen test. 


BIBLIOGRAPHY 


l. Zhironkin, A. G. “Oxygen: Physiological and Toxic Effects,” 
Leningrad, 1972. 


2. Comroe, J. H.; Dripps, R. D.; Dumke, P. R.; et al. J.A.M.A., Vol 128, 
1945, pp 710-717. 


3. Dolezal, V. PHYSIOL. BOHEMOSLOV., Vol 11, 1962, pp 142-158. 


58 








li. 


12. 


Matthys, U., and Buhlmann, A. A. SCHWEIZ. MED. WSCHR., Vol 100, 1970, 
pp 1313-1316. 


Krogh, A., and Leith, J. J. PHYSIOL. (London), Vol 52, 1919, 
pp 288-300. 


Ivanov, L. A. PAT. FIZIOL. [Pathological Physiology], No 5, 1976, 


Korkushko, 0. V., and Ivanov, L. A. KOSMICHESKAYA BIOL. [Space 
Biology], No 2, 1976, pp 45-50. 


Bishop, J. M.; Harris, P.; Bateman, M.; et al. CLIN. SCI., Vol 22, 
1962, pp 53-63. 


Agadzhanyan, N. A., and Kalinichenko, I. R. in "Gory i sistema krovi" 
[High Altitudes and the Blood System], All-Union symposium, Frunze, 
1969, pp 3-6. 


Zhironkin, A. G.; Panin, A. F.; and Sorokin, P. A. “Effect of High 
Partial Oxygen Tension on Man and Animals," Leningrad, 1965. 


Sorokin, A. A. in “Funktsii organizma v usloviyakh izmenennoy gazovoy 
sredy" [Body Functions in an Altered Gas Environment], Moscow-- 
Leningrad, Vol 2, 1958, pp 46-60. 


Rapoport, S. M. “Medical Biochemistry," Moscow, 1966. 


59 





UDC: 612.2+612.121.3]-06:612. 766.2 


EXTERNAL RESPIRATION AND ACID-BASE BALANCE OF HUMAN BLOOD DURING LONG-TERM 
ANTIORTHOSTATIC HYPOKINESIA AND IN THE RECOVERY PERIOD 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 42-46 


[Article by A. P. Golikov, V. Ye. Vorob'yev, V. R. Abdrakhmanov, L. L. 
Stazhadze, V. V. Bogomolov and S. G. Voronina, submitted 3 Feb 78] 


{Emglish abstract from source] 


The study of external respiration and acid-base equilibrium of blood of 35 test 
subjects exposed to 49-day head-down (—4) tilting and of 6 test subjects exposed to 
[82-day head-down (—4) tilting demonstrated a trend for a decrease in the —— 
rate, lung ventilation, oxygen consumption, and a relative increase in the exhalation 
time With respect to the arterialized blood gases, a significant decrease in Pao. an 
increase in Page and in the O, alveolar-arterial difference were seen during the 49-day 


head. down tilting During the 182-day head-down tilting a further increase in the CO, 
arterio-alveolar difference was noted. These changes suggest shilts of the ventilation- 
perfusion ration in the lungs and, probably. disturbances of central regulation of fes- 
piratior. icduced by head-down tilting. During the recovery period the above changes 
dimini-ived gradually and disappeared by the 14th and 30th day after the 49- and 182-day 


head-cown tilling, respectively. 


[Text] Studies have established that hypokinesia combined with anti- 
orthostatic [head down] body position (simulation of one of the most im- 
portant elements in the mechanism of effects of weightlessness on the 
body) induces changes in metabolic activity of tissues and gas exchange 
[1-5]. At the same time, the nature and severity of these deviations 
with increase in time of head-down position and hypokinesia have not 
been definitively determined. 


Our objective here was to make a comprehensive study of external respi- 
ration and acid-base balance (ABB) of blood in a series of tests involving 
prolonged antiorthostatic hypokinesia (ANOH) and studies in the subse- 
quent recovery period. 


60 











Methods 


We studied externai respiration and ABB in two series of studies involving 
49- and 182-day ANOH (-4°). 


In the first series with 49-day ANOH there were 35 essentially healthy 
males, ranging in age from 24 to 36 years. External respiration and 

blood ABB were examined at rest, in the morning of the background period 
(prior to ANOH), on the 30th and 49th days of ANOH, on the Ist, 7th and 
14th days of the recovery period. No preventive measures were used during 
the period of ANOH, and such rehabilitation measures as therapeutic 
physical culture, massage, regulated motor activity and hydrotherapy 

were used in the recovery period. 


Six essentially healthy men ranging in age from 33 to 39 years participated 
in the second series of studies; they were not submitted ‘> any special 
preventive treatment during the 182-day period of ANOH. * ‘ternal res- 
piration parameters and blood ABB at rest in the backg’ ».; d period, on the 
50th, 100th and 150th day of ANOH were used for analys « f the obtained 
data. 


Lung volume was examined on a META-1-25B spirograph; gas composition of 
exhaled air was determined with a capnograph and paramagnetic oxygen 
analyzer. Oxygen uptake was calculated by the open system method. 
Ventilation parameters were adjusted to the BTPS system. ABB and gas 
composition of arterialized capillary blood were examined by the Astrup 
micromethod. The difference in CO) and 0» tension for arterialized capil- 
lary blood and the last portion of exhaled air was considered as the 
respiratory gas gradient. 


The results of the studies were submitted to statistical processing. 
Results and Discussion 


In the background studies, all of the parameters used were in the normal 
range (see Table). On the 30th day of ANOH we found slowing and reduction 
of minute volume of respiration, relative increase in expiration phase, 
decreased oxygen uptake and coefficient of oxygen utilization (CU02). 


With reference to gas composition of alveolar air, there was a tendency to- 
ward decline of 02 tension and reliable increase in CO2 tension. Con- 
currently, a substantial decline of oxygen tension (P<0.01) and retention 
of carbon dioxide (P<0.05) were demonstrable in arterialized capillary 
blood. The arterioalveolar gradient for 0, increased by a mean of 6 mm Hg. 
Against this background, several subjects presented deviations in rhythm 
of respiration. 


In the first seiies of studies, by the end of the 49-day period of ANOH 
there was some tendency toward stabilization and even attenuation of the 


61 





demonstrated deviations of gas exchange and metabolism, which is probably 
related to emotional factors due te ~earing of the end of the ANOH 
period. 


Dynamics of some parameters of external respiration and acid-base 
balance in the course of long-term ANOH (Mtm) 
















































































os 
™U 
@ 
om | P s “ 

i a So S = 83 - 
a S a a 5 0 7 7 = 
41 7,9 .7 | 89.913.7 |40.2 |7,390] 23.9] ~0.5 

0.28 .22 | 0.89 10,2011.38 0. 0,14] 0.02 

35 7.3 9°82, 8°°13.1 33, 4°17,287] 24.4) 0.5 

0.26 61 | 1,09 10.31 11,54 10,009) 0.97! 0.03 
4] 7.5 40.9 | 8313.5 137.5 |7.390123.1)—1.2 
6,22 62 | 1,05 | 9.41 ]1,26 10,010) 0,20) 0,09 
6 7.1 7.5°1 85.3 13.2 136,0°17.376) 24.9| ~0.7 
0.27 45 | 3.07/0.19/2.32 }0,010) 0.41) 0.44 
6 7.8 8 | 82.7°13.2 |32.8°7.385) 24.7) --0.4 
0,19 19 | 1.66|0.16/2,07 |0,0101 0,56! 0,39 

Key: 


RR) respiratory rate (per min) 
MV) minute volume (2/min) 
PACO2, PAO2) CO2 and O02 tension in alveolar air (mm Hg) 
PaCO2, PaO2) CO2 and 02 tension in arterialized capillary blood (mm Hg) 
exp/insp) ratio of expiration phase to inspiration phase 
UO2) oxygen uptake (mi/kg/min) 
CU02) coefficient of utilization of oxygen 
SB) standard bicarbonates (meq/2) 
BE) base excess (meq/2) 


*Reliability of differences from background with P<0.05. 
**Reliability of differences with P<0.01. 


On the 100th and 150th days of ANOH, against the background of slower res- 
piration and decline of 02 tension in arterialized bleod, there was a 
tendency toward decline of oxygen uptake and CU02), concurrently with 
increase in CO» tension. Analysis of alveolar air revealed worsening of 
conditions for exchange of gases, as manifested by decline of CO2 tension, 
as compared to the 50th day of ANOH, with a tendency toward increase in 02 
tension. This was better Jemonstrable with retention of CO2 in arterial- 
ized blood and furthe cdc '‘ne of blood 02 tension. At this stage, there 
was an unbalanced exchange of gases, as indicated by the progressive 
increase in alveolar-arterial gradient and arteriolar-alveolar C02 
gradient (Figure 1). While exchange of carbon dioxide (according to 
equilibrium of CO) tension in alveolar air and blood) was adequate and 
adjusted to new conditions in the period up to the 50th day of ANOH, when 


62 








tested on the 100th and 150th days of ANOH there was a distinct tendency 
toward diminished efficiency of alveolar ventilation, as indicated by the 
significant difference in CO2 tension in blood and alveolar air. Figure 2 
illustrates the typical dynamics on the capnogram of subject P-v during 
prolonged ANOH. While there was c’ ose conformity of COz2 in alveolar air 
and blood (PACO2 46.0 mm Hg, PaCO2 47.6 mm Hg) on the 50th day of ANOH, 
which was indicative of efficient exchange of gases for C02, with increase 
in duration of ANOH there was dissc.iation of CO2 tension in blood and 
alveolar air (PACU: 40.6, PACO2 58.0 mm Hg on 100th day of ANOH; PaCO2 
40.0 and PaCOz2 53.0 mm Hg on the 150th day of ANOH), which was indicative 
of unbalanced exchange of gases. 


Figure 1. 
Dynamics of O2 and CO2 tension in 
blood under the unfluence of ANOH 


PaO2, PaCO2) O2 and CO2 tension in 
arterialized blood 
(solid iines) 
APAa02) alveolar-arterial gradient 
for 02 
SPaACO2) arteriolar-alveolar 
gradient for CO2 (dash 
f | line) 





P mas 
t I 
[ 


+ 







a 
is 
wa 


bad / 
$4 ---4 


ground ANOH, days 





It should be noted that these changes in gas composition of blood were not 
associated with substantial shifts of pH, which is attributable, to some 
extent, to compensatory change in blood buffer systems and, in particular, 
retertion of bicarbonates. We demonstrated a direct correlation between 
elevation of CO2 tension in blood and compensatory retention of standard 
bicarbonates (coefficient of correlation +0.77). As maintained by L. L. 
Shik [6], an increase or decrease in pulmonary and alveolar ventilation, 
with unchanged level of metabolism, could be of adaptive significance 
under a number of conditions, and may be indicative of a capacity to 
control respiration in accordance with the needs of the body as an integ- 
ral entity, even if this is related to deviations from stable PACO2, 
rather than a flaw in respiratory reguiation. 








The deviations in gas exchange 
under thei ifluence of prolonged 
ANOH are indicative of impaired 
ventilation-perfusion relations in 
the lungs. The gravitation factor 
has a substantial effect on the 
level of ventilation-perfusion 
relations, since the distribution 
of blood flow in the lungs changes 
substantially with change in body 
position [7]. Upon scrutinizing 
tue genesis of disturbances in 
ventilation-perfusion relations 
under the influence of prolonged 
ANOH, we can detect an increase 

in specific weight of inadequately 
perfused alveoli (nonperfused com- 
ponent or alveolar gas shunt), as 
well as functional atelectases of 
part of the lung parenchyma (un- 
ventilated component or vascular 
alveolar shunt [8]). At the same 
time, we cannot rule out a decrease 
in alveolar-capillary diffusion of gases, particularly in cases of hemo- 
stasis in the lungs. However, in view of the high diffusion capacity of 
CO2, it would be more correct to consider this a secondary mechanism in 
the genesis of deviations in gas exchange under the influence of prolonged 
ANOH. 





Figure 2. 
Capnogram of subject P-v during 
ANOH with slow (25 mm/min) and 
rapid (750 mm/min) recording. 
Explained in the text. 
1) background 
2-4) 50, 100 and 150 days of ANOH 


It is also important to mention the fact that there was no correlation be- 
tween minute ventilation and the main stimulus of respiration, CO2 

tension in blood (coefficient of correlation ranging from 0.162 to +0.134) 
on the 100th and 150th days of ANOH. This could be indicative of diminished 
sensitivity of the respiratory center to elevation of PaCO2 or of other 
mechanisms of deviation of central regulation of respiration. 


Thus, the observed deviations in exchange of gases under the influence of 
prolonged ANOH, being a special manifestation of functional adaptation to 
new living conditions, are apparently due to gravitational redistribution 
of body fluids [4], changes in central regulation of respiration and a 
change in conditions of pulmonary circulation [9], which leads to a change 
in ventilation-perfusion relations inthe lungs and, perhaps, decline of 
their diffusion capacity. The maintenance of relatively stable ABB under 
these conditions is indicative of adequate compensatory and adaptive 
capabilities of the body with gradually developing changes in exchange of 
gases. 


On the first day of the recovery period after 49-day ANOH with restriction 
of motor activity and orthostatic factors, the parameters of external 


64 








respiration and ABB of blood did not demonstrate appreciable dynamics, with 
the exception of a tendency toward increase in respiration rate and ventila- 
tion indices. On the 7th day of rehabilitation, we observed a decline of 
Oz and COz tension in arterialized blood, against the background of lower 
COz tension in alveolar air. With persisting tendency toward increase in 
gradient for 02, the gradient for CO2 was within the range of initial 
levels. At this time, the indices of O02 uptake and CUO2 remained low at 
rest, as compared to the background. Blood ABB at rest did not change 
appreciably. On the 14th day of the recovery period after 49-day ANOH, 

the indices of gas composition of blood and alveolar air were close to 

base levels. 


It should be noted that physical loads at the early stage of the recovery 
period after 49-day ANOH were associated with strained respiration for 

the purpose of maintaining adequate exchange of gases, and this was mani- 
fested by an increase in ventilation indices with decline of blood 02 and 
COz tension, as well as appearance of blood ABB change in the direction of 
mixed acidosis. Thereafter, at the next stages of rehabilitation, physical 
loads induced a more adequate reaction with reference to blood ABB and 
external respiration. 


At the early stage of the recovery period after 182~day ANOH, there were 
more marked disturbances referable to gas exchange and blood ABB, as 
manifested by low O2 tension in arterialized blood (75.0%2.46 mm Hg), as 
well as changes in blood ABB in the direction of metabolic acidosis. The 
metabolic disorders were probably due to hemodynamic, circulatory distur- 
bances at the early stage of readaptation. Under these conditions, we 
observed compensatory increase in pulmonary ventilation and increased 

CO2 output (PACO2 45.5%1.37 mm Hg). The high gradient for O2 (mean of 
18.4 mm Hg) was also indicative of diminished efficiency of ventilation 
during this period. The demonstrated changes gradually regressed there- 
after. However, low PaO2 levels were observed up to the 14th day of the 
recovery period. The parameters of external respiration and blood ABB 
virtually failed to differ from base values on the 30th day after ANOH. 


Thus, prolonged ANOH was associated with changes in external respiratory 
function. Extension of hypokinetic period ied to deterioration of con- 
ditions for exchange of gases. The dynamics of the parameters studied 

in the recovery period were indicative of reversibility and functional 
nature of the deviations in gas exchange under the influence of prolonged 
ANOH. 


BIBLIOGRAPHY 


1. Kovalenko, Ye. A. KOSMICHESKAYA BIOL. [Space Biology], No 4, 1977, 
pp 3-8. 


2. Katkov, V. Ye.; Kauricheva, V. V.; Chestukhin, 0. Kh.; et al. Ibid, 
No 5, pp 51-5/. 


65 





Kotov, A. N. KOSMICHESKAYA BIOL., No 2, 1977, pp 85-86. 
Belkaniya, G. S. Ibid, No 2, 1975, pp 3-8. 


Fedorov, I. V., et al. in “Aviakosmicheskaya meditsina™ [Aerospace 
Medicine], Moscow--Kaluga, Vol 2, 1975, pp 93-96. 


Shik, L. L. in “Fiziologiya dykhaniya" [Physiology of Respiration], 
Leningrad, 1973, pp 44-62. 


West, J. B. in “Advances in Respiratory Physiology," Baltimore, 1966, 
p 17l. 


Zil*ber, A. P. “Clinical Physiology for Anesthesiologists," Moscow, 
1977, p 15. 


Trushinskiy, Z. K.; Bogolyubov, V. M.; Anashkin, 0. D.; et al. 
KARDIOLOGIYA [Cardiology], No 12, 1977, pp 90-94. 


66 








UDC: 612.57-06:612. 766.2 


DISTINCTIONS IN DEVELOPMENT OF PYROGENAL FEVER IN ANIMALS FOLLOWING 
PROLONGED HYPOKINESIA 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 46-50 


{Article by P. V. Vasil'yev, G. D. Glod, S. I. Sytnik, N. N. Uglova and 
Y. P. Mel'nikova, submitted 22 May 78] 


[English abstract from source] 


The experiments on rabbits with pyrogenal fever and amidopyrine injection have 
demonstrated that their 15- and 30-day exposure to hypokinesia produces changes in 
the reactivity of thermoregulating centers, their overexcitation and depletion. These 


changes are more distinct after 15-day hypokinesia. 


[Text] Concrete data must be obtained about the distinctions of develon- 
ment of pathological processes in order to deal with the practical aspects 
of the problem of developing methods of diagnostics and medical care 

of diseases occurring during space flights. 


We have obtained some data on the effects of long-term restriction of 
movement on the course and development of inflammation [1] and hyperthermia. 


In this work, our objective was to investigate the distinctions of develop- 
ment of experimental fever in hypokinetic animals. It is known that 

fever, like inflammation, is among the typical pathological processes 
associated with many diseases, and it reflects the state of reactivity 

of the bouy as a whole and thermoregulation in particular. 


Met hods 


We used 48 male rabbits weighing 1.5-2 kg in our experiments. We produced 
15- and 30-day hypokinesia by putting the rabbits in special cages [2]. 
Fever was induced immediately after removing the animals from the cages. 
Standard pyrogenal [purified protein-free pyrogenic of bacterial origin] 
from a culture of S. typhi was injected in the lateral vein of the ear, 


67 





in a dosage of 1 MPD/kg. 





The state of heat regulation and sensitivity to 


pyrogenal were evaluated by the changes in rectal and ear temperature, 


heart and respiration rate. 


thermometry with an accuracy of *0.05°C. 


A copper-constantan thermocouple was used for 
In addition, we used in some 


experiments the indices of the EKG, EMG of lumbar muscles and peripheral 


blood. 


The obtained material was grouped and submitted to statistical processing. 


Results and Discussion 


The rabbits tolerated well the restricted mobility. 
constituted a mean of 129 and 171 g on the 15th and 30th day, respectively, 
The physiological parameters recorded 
at rest prior to inducing the fever did not differ appreciably from 

normal in experimental animals [Table 1). 


of hypokinesia in control animals. 


The lag in weight gain 





























Table 1. Physiological indices (Mtm) of rabbits at rest prior to injection 
of pyrogenal 
lumber | Temperature, °C Pulse | Respi- 
Group of | rate, | ration, 
animals | rectal {| oa per min | per min 
Contre: | 13 38,740.16 | 27,.92-0,.5 23947 132+17 
| 
| 
15th day of hypokinesia, 13 | 38,€-+0 16 | 27, 8+0.6 | 243+10 13629 
Control | 1 | 38,040.15 | 27,340,9 | 2337 127 +17 
: | | | — 
| ! | 
30th day of hypokinesia it ness] 27 ,7+1,1 249+10 i918 














The pyrogenal injection induced the febrile reaction that is typical for 


a single injection of this product [3]. 


For the first 30 min after the 


injection, the majority of rabbits presented a 0.1-0.3°C drop of rectal 


temperature, after which heat began to accumulate in the body. 


The 


maximum elevation of temperature was the same in experimental and control 


animals constituting 1.2°C on the 15th day of hypokinesia and 1.3°C on the 
30th day. However, the rate of development of hyperthermia varied. 

Thus, when inducing fever after 15 days of restricted movement the maximum 
temperature increment occurred on the average within 82*4 min and after 30 
days of immobility, within 109220 min. The fever developed more slowly 

in control animals, and the temperature peak occurred in the i5lst*l3 

and 130th*t19 min, respectively. The postpeak phase of the [rile 

cycle in experimental rabbits was characterized by a slower, sluggish 
course (Figure 1). The period of normalization of rectal temperature 


68 














constituted a mean of 72.4 and 63.8% of total time of temperature reaction 
in experimental animals, versus 49.8 and 55.5% in the control. 











2 Figure 1. 

e 124° P Dynamics of temperature reaction 

3 4 of experimental (15th day of hypo- 

3 os G2 kinesia) and control rabbits during 

2 0 Eo febrile period. Arrows point to 

E- ~ zt time of pyrogenal injection 

afte .- 1, 2) change in rectal and ear 

s° Pe —i_i_i_i_i— temperature, respectively 

8 Back ~/0 50 909010 20280290 in experimental rabbit 
ground minutes 3, 4) the same for control 

animal 


The results of thermometry of the ear are of some interest, as they were 
indicative of the functional state of physical heat regulation in the 
rabbits. Im the presence of fever on the 15th day of hypokinesia, maximum 
drop of ear temperature occurred simultaneously in both groups, reaching 
a mean of 3.7°C in the experimental group and 4.3°C in the control. On 
the 30th day, there was the same degree of decline (5.1°C) in ear tempe- 
rature, but there was faster inclusion of physical heat regulation in 
the febrile reaction in control animals. It is remarkable that the 
interval between minimum ear temperature and maximum rectal temperature 
was almost 3 times shorter in experimental animals than controls on the 
iSth day of hypokinesia and 1.8 times shorter on the 30th day. The 
changeover to heat transfer by ear vessels during the febrile cycle 
after 2 weeks of hypokinesia also occurred much sooner (in the 59th min) 
than in the control. By the 30th day this difference diminished sub- 
stantially. 


In order to assess the functional coordination of different elements of 
thermoregulation, we analyzed the correlation between changes in rectal and 
ear temperature. The febrile cycle was arbitrarily broken down into three 
periods: elevation (first), stabilization (second) and restoration (third) 
of rectal temperature. Table 2 lists the results of processing the data. 


Table 2. Coefficients of correlation between rectal and ear temperature 
of rabbits during fever 














| L5eday 30-day 
Period 
of fever | hypo- Contral; hypo-}|Control 
kinesia kinesiq 





| 0.9358 | —0. 7501 
| —0,3106 | —0,8347 
| —0,6374 | 0, 7981 


0.9279] ~0, 8704 
—) 2970! —0, 3.398 
—0 4365 | —0 8775 





whe- 








69 





Analysis of these data indicates that there was a closer correlation be- 
tween ear and rectal temperature during the period of temperature stabili- 
zation and restoration in control rabbits. In experimental animals, 

this function is less marked, which may be indicative of distinctive 
imbalance, of a change to another functional level of the mechanisms of 
heat regulation under the influence of hypokinesia. 


Analysis of the dynamics of heart 














beats/min and respiration rate (Figure 2), 
20} EKG and EMG during the access of 
2770+ fever led us to conclude that 

260+ the prior hypokinesia had no appre- 
250+ ciable effect on the above para- 
aso} meters. It should only be noted 

: that the level of cardiac contrac- 

a tions and respiration during the 
220 fever was usually somewhat 
cycles/min b higher in experimental animals 

130 F P than the control, i.e., injection 
"0 F of pyrogenal induced greater 

90 F strain on the cardiovascular system 
70 2 and less deviation of respiratory 
SOF rate from the base level. 

= oe ae ee | a cow 

Bone 10 a We know from the literature that 


heightened sensitivity to pyrogenal 
under the influence of any factors 
[4, 5] is usually associated with 
increased sensitivity of the heat- 
regulating center to antipyretics. 
In our experiments, hypodermic in- 
jection of amidopyrine in a dose 
of 100 mg/kg on the 15th and 30th 
days of restricted movement in- 
duced a substantial drop of body temperature (Figure 3). In experimental 
animals the maximum drop constituted a mean of 2.3°C and in controls 1.7°C, 
which could be indicative of heightened sensitivity of the former to 
antipyretics. 


Figure 2. 
Dynamics of pulse rate (a) and respi- 
ration (b) in rabbits during fever on 
l5th day of hypokinesia (mean data). 
Arrow indicates pyrogenal injection. 
1) experimental rabbits 
2) control animals 


Thus, under the influence of prolonged restriction of movement, there is 
shortening of the phase of temperature elevation and extension of the 
postpeak period of experimental pyrogenal fever. After 15 days of hypo- 
kinesia, these distinctions in development of the access of fever were 
more marked than after 30 days. Consequently, certain changes in func- 
tional state of the heat-regulating center develop in the course of im- 
mobilization: increased reactivity at the early stages of fever, mani- 
festation of torpidity and hyporeactivity of thermoregulation in the post- 
peak period of development of the process. There is impairment of coor- 
dination of function of different elements of this system, which apparently 


70 








leads to attenuation and, perhaps, depletion of functional capabilities of 
the center for heat regulation. The change in reactivity to pyrogenal under 
the influence of hypokinesia was associated with increased sensitivity of 
the centers to antipyretics as well. 


Figure 3. 
Dynamics of temperature reaction of 
rabbits after injection of amido- 
pyrine (15th day of hypokinesia). 
Arrow shows time of amidopyrine 
injection 





1, 2) change in rectal and ear tem- 
perature of experimental rabbit 
3, 4) same for control animal 


Rectal temp., 4% 





i i i .' a s. i -. = = 


“Back 10 5090139010 21025029030 
ground Minutes 





The works of P. N. Veselkin et al. [3] have demonstrated convincingly that 
development and course of the febrile reaction are determined primarily by 
the functional state of the central nervous system, correlation between 
excitatory and inhibitory processes in its higher branches. 


Yet it is known that hypokinesia worsens the functional state and adapta- 
tional capabilities of the central nervous system [5-7], and that inhibi- 
tory processes begin to predominate in the cerebral cortex [8-10]. 


In view of the foregoing, it may be assumed that, by virtue of the law of 
negative induction, there is “disinhibition” of subcortical vegetative 
centers, which cause increase in sensitivity of thermoregulatory systems, 
in the experimental rabbits. Moreover, under the influence of hypokinesia, 
the increased excitability is apparently combined with ready depletion 

of reactions, when maximum excitation of thermoregulatory centers is 
rapidly followed by inhibition thereof. 


In spite of the dominant role of neural mechanisms in formation of the 
febrile reaction, disturbances in the endocrine system in the presence of 
hypokinesia [11-13] may also change appreciably the reactivity of the 
heat-regulating system and, consequently, the body's capacity to induce 
fever under new and unusual conditions [3, 14]. 


Further investigations will definitely be needed for deeper study of the 
pathogenesis of the effect of prolonged restriction of movement on develop- 
ment of fever. 





13. 


l4, 





BIBLIOGRAPHY 


Vasil’yev, P. V.; Belay, V. Ye.; Gaydamakin, N. A.; et al. 
KOSMICHESKAYA BIOL. [Space Biology], No 4, 1977, pp 41-46. 


Savel’yev, T. P., and Krotov, V. P. Author Certificate 278291, USSR. 
Veselkin, 0. N. “Fever,” Moscow, 1963. 


Bystrova, L. N., and Kalinina, N. A. PAT. FIZIOL. [Pathological 
Physiology], No 3, 1973, pp 72-73. 


Medvedeva, G. I. FIZIOL. ZH. SSSR [Physiological Journal of the 
USSR], No 5, 1972, pp 750-753. 


Krupina, T. N.; Vedorov, B. M.; Benevolenskaya, T. V.; et al. 
KOSMICHESKAYA BIOL., No 2, 1971, pp 76-81. 


Ioffe, L. A. "Circulation and the Hypokinetic Syndrome," author 
abstract of doctoral dissertation, Moscow, 1971. 


Kareva, T. A. in “Aktual'nyye voprosy kosmicheskoy biologii i 
meditsiny" [Pressing Problems of Space Biology and Medicine], Moscow, 
1971, pp 129-131. 

Khruleva, L. N. KOSMICHESKAYA BIOL., No 6, 1969, pp 75-78. 
Reushkina, G. D. Ibid, No 2, pp 86-88. 


Kalandarov, S. in "Gagarinskiye chteniya" [Gagarin Readings], 
Moscow, 1973, pp 191-200. 


Fedorov, B. M., and Nevstruyeva, V. S. in “Predbolezn'" [Premorbid 
States], Moscow, Pt 2, 1969, pp 258-261. 


Lazarev, N. V., and Grachev, A. M. in “Voyen.-med. akad. im. 
S. M. Kirova. Vovyen.-nauch. o-vo slushateley. Itogovaya konf. 
Materialy" [Proceedings of Reporting Conference of the Military 
Scientific Society of Students, Military Medical Academy imeni 
S. M. Kirov], Leningrad, 1975, pp 105-106. 


Gurgenashvili, N. I. PAT. FIZIOL., No 3, 1974, pp 67-69. 


72 

















UDC: 613.155/.157:678.5/6 


RAPID LABORATORY METHOD FOR TESTING OUTGASING OF THERMOSTABLE PLASTICS AND 
RUBBER 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 50-54 


[Article by V. D. Yablochkin, G. D. Solomin, V. A. Shchirskaya, N. A. 


Glazkova, Ye. A. Demchenko, N. Ye. Ostasheva and E. I. Chukhno, submitted 
23 Jan 78) 


{English abstract from source] 


Time-temperature dence of concentrations of outgasing products of polymers 
and rubbers aa cuted pplyirg the principle of time — temperature equilibriuny, \- 
exposure time for a laboratory rapid study of polymers at 100 C was estimated - 
| br for enamels, lacquers and dyes, 1.5 hr for block and sheet polymers, 2 5 hr vd 
sealants and rubbers, and 4 br for textile materials, measured from the time when ¢ 

reassigned temperature was achieved The rapid method can be recommended for pre- 
Sieninats chemical study of polymers at the stage of their laboratory testing 


[Text] The migration of volatile substances in polymer materials and 
emission thereof into the environment is a diffusion process that is not 
governed by Fick's law [1], in which equalization of concentration of 

a substance that is nonuniformly distributed in the polymer follows the 
relaxation principle [2]. The previously expounded hypothesis [3] that 
relaxation of stresses in a polymer has an appreciable effect on the 
concentration of volatiles substances they emit subsequently gained 
experimental confirmation [4]. 


The study of relaxation processes in polymers made it possible to for- 
mulate the principle of equivalence or, as it is also called, temperature- 
time superposition [5], which means that the elevation of temperature 
affecting the polymer is equivalent to reduction of frequency of 

action of force or time of exposure to it. As shown by studies [6}, 
relaxation time is exponentially related to temperature, while the 
logarithm of relaxation time is a linear function of absolute reciprocal 
temperature. 


73 








The principle of time-temperature equivalence, which has been used in a 
number of cases for accelerated studies of the process of “aging” of 
plastics [7], can apparently also be applied (in view of the similarity of 
various relaxation processes) for rapid study of gas emission by polymers. 
However, as it has validly been noted [7], experimental methods for 
accelerated “aging” cannot provide for complete reproduction of natural 
“aging” of plastics, and for this reason any express method can be re- 
commended only for tentative evaluation of a group of similar materials 

in order to select the one with the best properties. 


A previous study [8] demonstrated the possibility of using a rapid method 
for examining th products of outgasing of polymers used for ornamental and 
finishing purposes. Our main objective here was to develop a method for 
rapid examination of thermostable polymers and rubber used in construction. 


Methods 


This study involved the use of metal containers that could be sealed, 

0.6 and 3.5 “in size, equipped with sleeves and rubber thermo- 
stable membranes to collect air samples with a syringe. The containers 
were kept in an incubator, in which there was automatic regulation of 
temperature (with an accuracy of *2°C) by means of electric heat through 
a water or air jacket. The temperature in the containers and incubator 
cabinets was measured and monitored by means of XA thermocouples connected 
to an cPP-09 potentiometer, and laboratory thermometers. We examined 
outgasing at temperatures of 40 to 100-120°C at 20°C intervals. At 

each temperature, we repeated the measurements every 30 min during an 
exposure period of up to 4 h (60-120 C) and every 1-3 days in the case 
of exposure for 10-15 days (in some cases up to 18-40 days; temperature 
of 40°C). We took 3-5 parallel readings at each point on the temperature 
curve. 


We selected for our study 29 samples of thermostable polymers and 
(including four textile fabrics, nine enamels and varnishes, seven 
samples of plastics in blocks and sheets, five sealers and adhesives and 
4 samples of rubber) manufactured on the basis of polysulfonimide, 
pyromellitimide, epoxy, melamine-formaldehyde and polyester resins, 
siloxanes and fiuvorine-containing elastomers. These materials contained 
organic solvents referable to the groups of alcohols, ketones, aliphatic 
and aromatic hydrocarbons, as well as esters, as volatile impurities. 
We used commercial samples that had been manufactured 3 months to 3 years 
prior to the study, containing different amounts of residual iow 
molecular components. 


In developing the conditions for rapid examination of polymer materials, 
we applied the principle of time-temperature equivaience, for which 
purpose we plotted summary graphs reflecting the concentration of pro- 
ducts of outgasing as a function of exposure time at different 
temperatures, until they conformed with the selected equilibrated level. 


74 





This procedure enabled us to evaluate the entire range of exposures at 

the selected temperature. In this regard, previously described methods 

of gas chromatography [3] were used to analyze the qualitative and quanti- 
tative composition of the products of out gasing of thermostable polymers 
and rubber at standard saiuration (1 kg/m or 1 m’/m*’). The objective 

was to choose optimum temperatures and exposure times, with which the 
qualitative and quantitative composition of outgasing would not differ 
appreciably from the composition of equilibrated concentrations at a 
temperature of 40°C. 


Results and Discussion 


It was established that there is an increase in concentration of volatile 
substances with increase in temperature and exposure, and the nature of 
outgassing is graphically described by a linear or exponential function 
(Figures 1-4). At a temperature of 60°C and exposure time of 4 h, the 
concentrations of volatile substances did not usually reach the equili- 
brated levels obtained at 40°C (exposure time 10-15 days), while at 120°C 
the initial concentration of volatile substances after exposure for 30 min 
was considerably higher than the equilibrated. Such patterns were 

noted when we tested polymers referable to most of tie groups studied; 
for this reason, although the products of thermal oxidative destruction 
could not be demonstrated, even with the top temperature of 120°C, we 
could only select the range of 80-100°C for rapid testing of most of 

the materials. However, at a terperature of 80°C, exposure of the 
samples to “sealing” constituted more than 4 h in many cases, therefore 

a temperature of 100°C was the most common and convenient condition for 
testing materials from different groups. 


C, mg/or 


no \- Figure 1. 
Cencentration of volatile sub- 
stances emitted by enamel based on 
epoxy resin as a function of 
exposure time 


1, 2) butylacetate (100 and 120°C, 
3 respectively 
3) ethylbenzene (100°C) 
1*-3') respective levels of equi- 
. librated concentration 
—— at 40°C 
ht 


— 7 = ee a “a * 


- 





ss8eQs8s8 


~ 
>) 
Te 








>) 


IS LOL! 20253,0354¢0T, h 


a ’ 








Exposure time was chosen in the time interval of 40 min to 4 h, and it 
was defined as the result of intersection of the curves of outgasing 
at 100°C on the curve of concentration of volatile products as a func- 
tion of exposure time [to sealing] with a base line corresponding to an 
equilibrated level of concentrations of the component in question at a 
temperature of 40°C, which was usually established in the sealed con- 
tainers on the 7th-15th day. 











C, ng / nt | Figures 1-4 illustrate the re- 
$0 sults of studying outgasing of 
oS some materials as a function of 
40 their exposure to sealing. As 
2s can be seen from the submitted 
20 data, the time the outgasing 
25 curves reach an equilibrated 
level is related not only to the 
co type or group to which a material 
S belongs, but chemistry of the vo- 
10 volatile component, and it is the 
5 latter circumstance that presented 
3 difficulties in selecting the 
OS 1,0 5 2.0 2.530354,0T,h exposure time for rapid testing 
of materials in different groups. 
Figure 2. Evidently, under such conditions, 
Concentration of acetone discharged one could only choose some average 
from carbon-containing plastic as a or maximum exposure time, with 
function of exposure time due consideration of possible 
1-3) 60, 80 and 100°C temperatures, variations in chemical composition 
respectively of the complex of products of 
Dash line refers to level of equili- outgasing from polymers in a given 
brated concentration at 40°C group. Evidently, the differences 


in time of attainment of an equi- 
librated level could be attributed to the distinctions in diffusion of 
chemicals in the materials and their quantitative content in the tested 
samples. Model samples of polymers and rubber with a specific amount of 
volatile impurities (0.25 to 1%) were prepared for experimental verifica- 
tion of the distinctive features of the effect. As a result, it was es- 
tablished that there was no appreciable difference in time of attainment 
of equilibrated level with increase to 1% in styrene content in a 
rubber sample based on butadiene-styrene rubber at 100°C. The same was 
observed in the case of rubber based on fluorine-containing elastic (see 
Figure 3) at temperatures of 80 and 100°C, with 0.5 to 1% hexane content; 
however, in the range of 0.25 to 0.5% at a temperature of 100°C, we ob- 
served some increase in exposure. It should be noted that the concentra- 
tion factor was very important in the case of low levels of vo’atile 
products in the material. Thus, sealing time constituted up to 4 h 
for fabrics containing trace amounts of volatile products, whereas for 
enamels, where the residual level of volatile substances reached several 
percentage points, it did not exceed 1 h. 


76 








C,mg/m°* Figure 3. 











12 + 3’ Concentration of n-hexane discharged 

"wt by samples of rubber based on 

10 + s2' fluorine-containing elastic con- 

gt taining different amounts of vola- 

at tile components as a function of 

> | 43 exposure to sealing 

6 | 2 1, 1°) 0.25% concentration at 80 and 

4 ao 100°C, respectively 

4 ee = 2, 2") 0.5% concentration at 80 and 
' ’ A 100°C 

J 7 3, 3°) 1% concentration at 80 and 

eT 4 VE of - 100°C 

’ or 1"-3") corresponding levels of equi- 





9 


librated concentration at 


ID 1.5 2.025 3, 40T, 
05 10 1.5 20253,035 h 40°C 





C, mg/m; 
700 
600 ' 
Figure 4. 
500 Concentration of volatile substances 
discharged by plexiglas based on 


polymethyl methacrylate (at 100°C) 
as a function of exposure of sample 
to sealing 


2 1) methanol (D = 0.24°107* cm*/s) 
2) ethanol (D = 0.24°107* cm*/s) 
3) benzene (D = 5.50°107° cm*/s) 
i'-3') corresponding levels of 
4 equilibrated concentration at 
= a =? 40°C temperature 


0510 1,5 20253.035¢0T,h 








Another factor that has some influence on exposure time is the rate of 
diffusion of substances in the material, which is determined by coeffi- 
cients of diffusion that have been studied experimentally for a small 
number of chemicals as related to widely used polymers. We tracked the 
significance of this factor on the example of a model sample of plexiglas 


i7 








based on polymethyl methacrylate containing as impurities methanol, eth-nol 
and benzene, for which the values of coefficients of dif.usion are known 
[9]. As can be seen from the curves illustrated in Figure 4, the time 

of attainment of an equilibrated level constituted 15-20 min for methanol 
and ethanol (coefficient of diffusion D = 0.24°107* cm*/s) and 4 h for 
venzene (D = 5.5°10-" cm/s); for this reason the chioce of exposure time 
for rapid testing of this material could be made only on the basis of 
calculation of the mean time of attainment of equilibrated levels of 
components of outgasing inherent in a given sample. Calculation of mean 
sealing exposure times for materials referable to different groups yielded 
the following values (in min): 225°15 for fabric, 49°15 for enamels and 
other varnishes, 84°15 for block and sheet plastics, 85250 for adhesives 
and sealers, 109°41 for rubber. 


Thus, the rapid testing of thermostabie polymers and rubber can be done 
at a temperature of 100°C and exposure time of 1 to 4h for different 
groups, which reduces significantly the time required for laboratory 
testing, which is currently performed at a temperature of 40°C and 
requires 10-15 days. Exposure time should be counted from the moment 

a specified temperature has been reached for the material, while the con- 
centration of volatile substances formed in the gas environment and 
demonstrated at that time should be considered as background and deducted 
from the final results. It is quite obvious that this procedure implies 
the use of high-speed instrumentation for analysis, which is highly 
sensitive aid specific and does not require large volumes of air for 

the analyses. When running rapid tests, the choiceof other experimental 
parameters (temperature and exposure time) can be made on the basis of 
the logarithm of exposure time of a sample as a graphic function of the 
reciprocal of absolute temperature, which is linear, as was shown by the 
results of experiments with various materials. 


in conclusion, it should be noted that the findings from testing samples 
1t materials referable to each of the groups do not serve as sufficient 
grounds to derive a categorical conclusion concer:.ing the time required 
for rapid ["express”] testing thereof. For this reason, as experimental 
data are accumulated in the course of work dealing with sanitary and 
chemical testing of new polymers, there may be some adjustment and 
further definition of exposure time [for sealing} for materials referable 
to different groups. 


BIBL LOGRAPHY 


4 


i. Reytlinger, S. A. “Permeability of Polymers," Moscow, 1974. 


2. Vasenin, R. M., and Chernova, I. V. VYSUOKOMOLEKULYARNYYE SOYEDINENIYA 
High Molecular Compounds], No 11, 1966, pp 2006-2011. 








3. Jablochkin, V. D., et al. REV. MED. AERONAUT., Vol 12, 1973, 
pp 305-308. 


4. Khofbauer, E. I.; Bebchuk, T. S.; et al. ZH. PRIKLADN. KHIMII 
[Journal of Applied Chemistry], No 2, 1976, pp 391-396. 


5. Aleksandrov, A. P., aud Lazurkin, Yu. S. ZH. TEKHN. FIZIKI 
[Journal of Industrial Physics}, Vol 9, 1939, p 1249. 


6. Lazurkin, Yu. S. Ibid, pp 1261-1266. 


7. Pavlov, N. ©. in “Pererabotka plasticheskikh mass" [Processing of 
Plastics], Moscow, 1966, pp 249-253. 


8. Demchenko, Ye. A.; Glazkova, N. A.; Chukhno, E. I.; et al. in 
"Aktual'nyye problemy kosmicheskoy biologii i meditsiny" [Pressing 
Problems of Space Biology and Medicine], Moscow, Vol 1, 1977, 
pp 8-9. 


9. Zhurkov, S. N., and Ryskin, G. Ya. ZH. TEKHN. FIZIKI, Vol 24, 1954, 
pp 797-810. 


79 








UDC: 612.112.94.014.24.014.482.2 


EFFECTS OF 25 AND 50 MeV PROTONS ON HUMAN PERIPHERAL BLOOD LYMPHOCYTE 
CHROMOSOMES IN VITRO 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 54-60 


[Article by A, M. Totseva, N. I. Ryzhov, V. N. Gerasimenko and Ye. 
Dermendzhiyev, submitted 21 Feb 78] 


{English abstract from source] 


The frequency and type of chromosomal abberations in human lymphocytes induced 
by 25, 90, 645 MeV protons and 200 ky x-rays were studied. It was shown that the vield 
of one-hit acentric iragments increased linearly and that of double-break aberrations 
increased ¢xpomentialiy with the irradiation dose. It was demonstrated that under the 


influence of radiations with high linear energy transfer the number of paired fragments 
increased and that of dicentrics and rings decreased. The test of total yield of chromo- 
somal aberrations and their specific types helped to derive coc ‘fictents of relative biolo- 
gical effectiveness of the above irradiations. There was a qua..titative correlation bet- 
ween the dose and vield of individual aberration types This suggests that lymphocytes 
can be used as a biological dosimeter jor dose measurement. 


{Text} In our preceding report [1] we submitted the results of a study 
of radiation damage to the chromosome system of human lymphocytes under 
the influence of 645 MeV protons. We demonstrated the nature and main 
parameters of yield of different types of chromosomal aberrations as a 
function of dosage. It was shown that the coefficients of relative 
biological effectiveness (RBE) are close to 1 for protons, according to 
incidence of single and double breaks, as well as total yield of aberra- 
tions. The fact that these studies were conducted on human lymphocytes 
and that there was a clearcut quantitative identity of effects of in vitro 
and in vivo irradiation of lymphocytes enabled us to extrapolate, with a 
nigh degree of reliability, the data obtained for the RBE of 645 MeV 
protons to the integral human body, and to use them to set standards for 
radiation exposure during space flights [2]. 


The presence of protons with lower energy in space radiations served as 

the grounds to continue these studies in order to obtain information about 
the biological effects of such radiation on the chromosome system of human 
lymphocytes. 


80 








In this work, we analyzed the results of studies involving exposure in 
vitro of cultures of human lymphocytes from peripheral blood to 25 and 
90 MeV protons. Some of the preliminary results of the studies were 
reported in previously published works [3, 4]. 


Methods 


Lymphocytes trom human peripheral blood were cultured by the method of 
Moorhead et al. [5] with some modifications [6]. The cultures were 
exposed to radiaticn in doses of 25, 50, 100, 200 and 400 rad 3-6 h after 
addition of phytohemagglutinin. X-rays were delivered at 200 kV, 15 mA 
and dose rate of 0.95 rad/s. The synchrocyclotron of the Joint 

Institute of Nuclear Research (Dubna) was used to deliver protons. The 
dose rate of 50 and 25 MeV protons constituted 0.40 and 0.35 rad/s, res- 
pectively. Culturing lasted 2 days at 37°C. The cultures were treated 
with colchicine in a concentration of 5 g/m after 48 h and they 

were fixed 3 h later. The preparations were stained according to Giemsa. 


We selected for analysis metaphase plates with well-dispersed chromosomes. 
We analyzed the quantitative chromosomal changes and structural aberra- 
tions of chromosomes. Chromatid and paired acentric fragments were 
classified as singie-hit aberrations, while double-hit ones included 
dicentrics and rings with one paired fragment, interstitial deletions and 
translocations [7]. Genes were not taken into consideration in the 
analysis. 


Results and Discussion 


The results of our study of radiation-induced genome mutations revealed 
that the yield of aneuploid cells depended little on dosage and did not 
substantially exceed 10% of the cells examined (Table 1), within the 
error margin of the experiment, under the influence of all tested levels 
of proton energy. It is believed [8, 2] that the presence of such cells 
in the first mitosis is related primarily to the technique used to make 
the preparations. We believe that one should also not rule out the 
possibility of induction of aneuploid cells as a result of the effect of 
radiation. We base this conviction on the presence of a tendency common 
to proton of all tested energy levels coward approximately twofold in- 
crease in yield of cells with altered chromosome number (referable to 
polyploidy and endoreplication) with increase in dosage from 25 to 

400 rad (Figure 1). 

Table 2 lists the results of the study of chromosomal aberrations of dif- 
ferent types and forms thereof as a function of dosage of radiation and 
energy of protons. For the sake of comparison, data are given on struc- 
tural chromosomal aberrations of lymphocytes when exposed to 645 MeV pro- 
tons and x-rays. We must call attention to the low yield of chromatic 
aberrations, as well as the fact that it is independent of radiation dose, 
proton energy or type of radiation. 


81 








Table 1. Quantitative chromosomal changes 





% 


Type of 
radiation 


Dose, 

rad 

Total | 
© janeuploid 
w |cells, 





w 


X-rays | 
Protons, MeV: 
64 
50 
25 
X-rays ~ _ 
Protons, MeV: 
b49 


50 
25 — 
Xerays | —j— 
Protons, MeV: 
645 


Control 
| | 
; | 

| S| 
uv 


o 





to 
uw 
to 
—) 
, QDy 
uw 


“te oO oo aw 


Progons, MeV: 
64 
50 100 —_ 1.0 
25 -- 0.5 
X-rays - _— 
Protons, MeV: 
H45 


1,5 
50 200 | 1.0 

! 

l 


euUocoeo FOO Www oO 


NW Ul a 














“cr 


at 
~— 


' 
-~ so) 1 
ou 


Jt 


- 


A~rays 
Protons, MeV: | 
645 2.0 | 


' 
; | 

50 4% oe | 2.0 10.5 
| | 


- 
- 
. 
“Le 


—_ 


° 
S 


25 








The yield of paired acentric fragments as a function of radiation dosage 
is clearly linear (Figure 2), for both the three energies of protons and 
X-rays. Data processing by the least squares method revealed that the 
dose-effect function for paired fragments is well approximated by the 
equation Y = 2D", where Y is the yield of paired fragments (%), D is the 
radiation dose (rad), @ is the coefficient of proportionality and ” is 
the hit index. For paired acentric fragments, we obtained the following 


equations: 


Y25 MeV = 2,08.10-2. pi®. 98 20,09 (I) 
Pen ue gs | £9 1h- (1,034+0,09 

¥50 MeV 1 ,42-10~3 D . (2) 

‘645 MeV = 0,93-10-3.p{-06 £0.22), (3) 


| 


y = 1,0620, 
roentgen 0,85. 10-9.pr-™ aa (4) 











‘iby 
. “ 











Aiwa R 
200 400 D rad 
Figure |. 
Yield of aneuploid cells as a function Q jap 8 rad 
of radiation dose. Here and in Figures , 
2 and 3: triangles--x-rays; squares-- 
protons with energy of 25 MeV; black Figure 2. 
and white circles--protons with Yield of paired acentric fragments 


energy of 50 and 645 MeV, respectively as a function of radiation dose 


We can interpret the linear correlation between yield of paired acentric 
fragments (single-hit breaks) and radiation dosage on the basis of the 
classical conceptions of quantitative radiobiology [9]. A comparison 

of equations (1-3) also indicates that there is an increase in yield of 
single-hit aberrations with decline of proton energy. It is quite diffi- 
cult to provide a satisfactory explanation for this effect, in wiew of the 
Significant complexity of the intimate mechanism of developmert of chromo- 
somal damage. Evidently, the increase in proton-proton interaction and 

in linear energy transfer (LET) are responsible for the demonstrated 
changes in yield of single-hit aberrations. The significance of LET of 
radiation in induction of the above aberrations has been discussed rather 
comprehensively in previously published works [10, 11}. 


Figure 3 illustrates the dose functions referable to double-hit chromosomal 
aberrations for x-rays and protons differing in energy. We determined the 
overall yield of dicentrics and rings. The yield thereof as a function of 
dosage of radiation for protons and x-rays can be described by the follow- 
ing equations: 


Yos mey = 1.01. 10-4. pl!. 9520.16), (5) 
Ys0 Mev = 1.53-10-4.pt.#20,14), (6) 
Y645 MeV = 1.80.10~4 pit 4020.08), 7) 
ae 0.98. 10-4 pl!.50 +0. 10) (8) 


83 



















































































Table 2. Incidence of chromosomal aberrations 
" 7 7 . 
Type of chromosomal 
= 19% om is 
* 
z Co +y 5x” 55 o” 2 
fe Be B5) eI" [ea] 52 3a . 
wee OS fede 2 | 8 S835ltaisels [oeSies 148 142 
radiation Vieciod Se volauloulm |oeelas ek aa 
S/S Eo¥esianigcis |zcelea [5s |e x 
SIOUOD j on So lobi55 re |526 Saean |E5 
X-rays 300} 2.3) — |}—|;—|—|]—] — | 
pestane, tel 2.3) 2.3) 2.3 
645 200| 3 —j|/—j|—|j—| — | 3 3 
50 0 | 200) 2 — |}—-|—|—-|—/| — | 2 2 > 
25 200; 2 —_i- dl bes —_j— 2 2 2 
X-rays 200} 2.5 | _ _ _ 
Protons, MeV: . om | ' ’ ’ ° 
645 200) 3 3 j-j2];— 7.5) 8 
50 25/200} 2.5) 45'—/!2 |—-|-—| —]| 8 9 "1 
25 200 3 5.5 |0.5) 0.5, —| * 9.5) 10.5 
X-rays 
Protons, MeV: | 200) . s |! aoe oe ee ee an ae ld 
645 /200) 2 5.5/0.5) 45/—/0.5) — |11,5/ 13 | 185 
30 50/2001 4 | 9 |~13'5 —/0.5); — [13 17 | 2 
25 }200; 2 | 9.5/0.5) 2 | — (0,5 12,5) 14,5) 17.5 
\-rays > 5! a | | | - 
rotons, MeV4 (260) 2.7 | 12 it 73 — {1,5} 0.7 [23 | 25.7) 36,7 
645 200, 3 =| 11,5 ),2,5/)9 l i 25 28 $1 
50 y00]200) 1 15° {1} 7 | — | —1 9.5 | 17,8] 24.5) 3 
25 | [200) 2,5 | 18 ' 6 | —j-) os | ae | 38 «35,5 
A-rays 900 | 3.5 | 24 17.598 _— 5 
Protons, mv | | 5 | | - 3 1, 48 64.5) 101.5 
645 500) 2.6 | 29.4°7.531 |— 12,5) 1 | 52 | 73.5) 115 
50 }200/200/ 2:5 [38° [2.54 |—)2] 1 | 30,5] 56° 73.8 
2 | }200) 5 137) [2 0,5) - 12,5) 1 | 46,5) 58 | 74 
awrays lead a 42,5 |15 '65 islia | as | 79 5.5/2 
Protons, Mev i* >. | ) ’ . ‘ 146.5 249.5 
645 | jroo} 2 | si [20 leo |2 tag ta fas fas9 | 269 
50 | 400 | 200. 3 {7i | 7 | = 6 | 3 68 |135 | 196 
25 100) 4 | 74 SO j—)} 412 | 8 | 122 | 166 











Analysis of equations (5-7) shows that there is a decline in yield of di- 
centrics and rings with increase in LET. The overt nonlinear nature of 
yield of aberrations as a function of dosage and obtained values of n<2 
are consistent with the data of other authors [12, 13]. Since intra- and 
inter-chromosomal exchanges are double-hit aberrations, one should have 
expected the correlation to dosage to be quadratic in equations (5-8). 
However, in view of the fact that a certain share of the exchanges 

occurs in the presence of two injuries induced by passage of one particle 
(9), as well as the result of postradiation repair of some chromosomal 


lesions [14], there occurred the deviation that we observed in » from 2 





84 








in the direction of a decline. 


As to the correlation we observed in the 


experiment between overall yield of dicentrics and rings, on the one 
hand, and proton energy, on the other, we can concur with the authors 
[9, 15] who assume that the yield of interchromosomal exchanges depends 
on the mean distance between rather closely situated segments of chromo- 
somes which, in turn, is determined by the range and LET of protons, and 


secondary ionizing particles. 


We cannot rule out the possibility that 


there is also a change in nature of damage to chromosomes with decrease 
in proton energy, as a result of which the probability of expression of 


exchanges diminishes. 


* / 
wo! , 
al 
| / 
40: | 
P 
20 - oo 





oe 


200 





Figure 3. 
Overall yield of dicentrics and rings 
as a function of radiation dosage 


that is required for practical purposes. 


As previously indicated, the sensi- 
tivity of chromosomes to radiation, 
prolonged retention of cytogenetic 
«ffects, approximately the same 
cuantitative and qualitative 
effects of in vitro and ir vivo 
irradiation of human lymphocytes, 
as well as a number of other fac- 
tors, have resulted in using human 
lymphocytes as a “biological dosi- 
meter.” Dose-effect functions 
were obtained for different types 
of ionizing radiation over a wide 
range of doses and energies, and 
they make it possible to define the 
radiation dose and, accordingly, 
severity of radiation lesion to 
man according to yield of chromo- 
somal aberrations of different types 
types with the degree of accuracy 
There are different opinions as 


to the type of chromosomal aberration that should be used to determine the 


radiation dose. 
and rings, the yield of aberrant cells, 
number of aberrations per aberrant ceil 
most 
the total yie d of 
our experiments, parameters of the dose 


In essence, these are single-hit aberrations, dicentrics 


total number of aberrations and 
[16-18]. Ewvtdently, one of the 


important criteria for assessing the severity of radiation damage is 
chromosomal aberrations. 


According to the results of 
function for this criterion were 


obtained, and they are represented in the following equations: 


"25 MeV = 2,89.10-3.pl.94 20.09). @) 
Y50 MeV =. 2,20.10-3 D'' 0020, 10) (10) 
1645 MeV = 1.90. 10-3. p!!.02 20,10) (i!) 
‘roentgen 1,70. 10-3. pli.02 20,08) (12) 








Analysis of these data demonstrates the significant resemblance of the 
dose function, in essence for all radiations studied, the great closeness 
to 1 of the values of “hit” coefficients, and this enables us to use the 
equations for determination of dosage according to magnitude of the bio- 
logical effect. At the same time, it should be noted that the significant 
concentration of initial segments of the dose curves together, correspond- 
ing to the effects of relatively low doses of radiation, will most 
probably contribute substantial difficulties in identifying the type 

and energy of radiation. However, in the case of high doses, identifica- 
tion of proton energy could be made easier with availability of informa- 
tion about the ratio of single-hit aberrations to double-hit ones, which 
differ significantly in the range of tested proton energy. 


Table 3. RBE coefficients for 25, 50 and 645 MeV protons 











Proton 
energy, 
Mev 








645 
530 
25 








Equations (9-12) also make it possible to obtain the RBE coefficients for 
25, 50 and 645 MeV protons. in principle, equations (1-8) can also be 
used for this purpose. However, analysis of the data in Table 2, Figures 
2 and 3 indicates that the RBE coefficients for 25 and 50 MeV protons 

are different for different chromosomal aberrations; moreover, the 

values of RBE are also different in different doses ranges for dicentrics 
and rings, the yield of which is a nonlinear function of dosage (Table 3). 
For this reason, it is preferable to use the data on total yield of 
aberrations in order to determine the RBE for 50 and 2° “+«V protons. 
According to this criterion, the RBE for 25 and 50 MeV ons constituted 
1,0*0.1 and 0.9820.07, respectively. 


Thus, our studies revealed that exposure of human lymphocytes to 25, 50 and 
545 MeV protons in vitro induces various types of chromosomal aberrations 
in them. In all cases, we observed a linear increase in single-hit 

and gradual increase in multihit aberrations with increase in dosage. It 
was also shown that there is an increase in paired fragments, as well as 
a decrease in vield of dicentrics and rings, under the influence of 
radiation with high LeT. There was a quantitative correlation between 
dosage and overall yield of aberrations, which suggests that lymphocytes 
could be used as a biological dosimeter for determination of dosage. The 
RBE coefficients for 25 and 50 MeV protons were determined from the 
criterion of total yield of aberrations, and they were found to equal l. 


86 








15. 


16. 


l/. 


18. 


BIBLIOGRAPHY 


Ryzhov, N. I., et al. KOSMICHESKAYA BIOL. [Space Biology], No 3, 
1973, pp 79-83. 


Bechkov, N. P. “Human Chromosomes and Radiation,” Moscow, 1971. 
Totseva, A. M. in “Bolgarskaya natsional'’naya konf. po med. genetike 
i biologii” [National Bulgarian Conference on Medical Genetics and 
Biology], Varna, 1972, p 55. 

Idem, “First Worldwide AMIE Congress," Varna, 1972, p 167. 

Moorhead, P. S., et al. EXP. CELL. RES., Vol 20, 1960, pp 613-618. 


Gol’dman, I. L., and Levina, L. Ya. BYULL. EKSPER. BIOL. [Bulletin 
of Experimental Biology], No 11, 1964, pp 103-107. 


Bochkov, N. P., et al. GENETIKA [Genetics], No 5, 1972, pp 133-141. 


Antoshchina, M. M. RADIOBIOLOGIYA [Radiobiology], No 1, 1968, 
pp 89-91. 


Li, D. Ye. “Effect of Radiation on Living Cells," Moscow, 1963. 


Sevan'kayev, A. V., et al. in “Radiatsiya i organizm"” [Radiation 
and the Organism], Obninsk, 1975, pp 93-94. 


Lloyd, D. C., et al. INT. J. RADIAT. BIOL., Vol 28, 1975, pp 75-90. 


Sevan'kayev, A. V., and Bochkov, N. P. GENETIKA, No 5, 1968, pp 130- 
137. 


Todorov, S., et al. MUTAT. RES., Vol 15, 1972, p 215. 
Dubinin, N. P., and Tarasov, V. A. in “Sovremennyye problemy 
radiatsionnoy genetiki" [Current Problems of Radiation Genetics], 


Moscow, 1969, pp 7-78. 


Wolff, S., et al. J. BIOPHYS. BIOCHEM. CYTOL., Vol 4, 1955, 
pp 368-374. 


Bender, M. A., and Gooch, P. C. RADIAT. RES., Vol 29, 1966, 
pp 568-582. 


Norman, A. in “Human Radiation Cytogenetics,” Amsterdam, 1967, p 53. 


Sasaki, M. S., and Miyata, H. ‘ATURE, Vol 220, 1968, pp 1189-1193. 


5/ 




















UDC: 574,682:621.398 


DEVELOPMENT OF PROGRAM FOR THE CONTROL OF THE AUTOTROPHIC COMPONENT OF 
AN ECOLOGICAL SYSTEM THAT IS CLOSED WITH REGARD TO EXCHANGE OF GASES 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 60-63 


[Article by A. S. Nasonov and V. S. Toroptsov, submitted 3 May 77] 
[English abstract from source] 


The requirements for the programmed control and performance of autotrophic and 


heterotrophic components of a closed ecological system were determined. Stability of 
the system can be assured. if these requirements are met. The paper gives examples of 
pertinent computations 


[Text] This work completes the study of programmed control of the auto- 
trophic element, which we began previously [1]. We have defined the 
set of requirements that must be imposed on the parameters of programmed 
control and productivity of components in order to create a system that 
would be stable in exchange of gases. 


Definition of the Control Program 


in order to define the control program within the range of a specified 
cycle for system operation, T. = Ti +T2, let us estimate the time Tt; and 
tg of operation of the autotrophic component in each of modes I; and I>. 


From system (2) [1], with consideration of the expressions for mean 
volumetric rates of oxygen output and carbon dioxide uptake by the auto- 
trophic component in time T,, we obtain: 


rs “ = - - 
ve'iy) be Vy, ~ve'(y) ~ Ve, 
t, iS). Se )6=—|l (1) 
iG) ve (=v iy) VG) * 
% I. ~+ Ty. (2) 


88 











In viewof the fact that 0<1,< 7T,, we shall have: 


vig) Novy - vide) S va, 
0< . _— ; - oo . «il, ® 
ve' ty) ver) — ve) 





which can be transformed to the following appearance: 


* 

> Vz,-(Re—e") (4) 
0<y= = : - <i, ; 
vet ig). (re? —r"") 





where Y is the share of autotrophic element operating time in mode I>, 
within the range of the set cycle, and Rr is the coefficient of respira- 
tion of the sum of heterotrophic components: 


r°'~-photosynthet ic coefficient of autotrophic componen* in mode I, 
| veiw) 
es “OTT |e 
ve &) 
r° *--photosynthetic coefficient of autotrophic component in mode I, 


vi? (y) 
\ = VIG)’ 


The share of operating time for the autotrophic component in mode I;, 
within the range of the set cycle is 8 = 1 = y. 


Thus, equation (4) is a mandatory and sufficient condition for creating 
a stable system, closed for gas exchange, for two modes of operation. 


The above proof of stability will also be valid for the case when the 
second mode Il? is referable to darkness: 


const<<O u V8? (y jx VO? = const. 


89 











In this case, condition (4) can be written down in the following form: 


0? 

Re—™ Ve 
o> —a > : 

>: 

i=] : 


In this case, if functions y*'(y)& vo'(y) are submitted in the 
following form [2]: ve" (9) : v*! G— 4): 


Ve'(y) = ar -(y— Ad =v (y—A), 


where ¥°'>0,v°'>0 54>0. the operating time of the autotrophic com 


ponent {n each mode is determined as follows: 


- 

vy > Ve, = ‘ 

iel ioel 
Ai .A2 Ai 2 
Ve -V, = Ve Vy 


7 
,O1 \, , 
= 4 > Vy, 





Determination of Mean Stationary Concentrations 


Let us now consider the mean stationary values that the concentrations 
of carbon dioxide will assume, y; (i = l, n). 


From (3b) [1] we have: 


~ = Vyly)—Vy, /o 
Tr hn 4 i (6) 





Here, y is determined from the mandatory stability [stationary] conditions 
tb) {i}. 


us, the mean stationary values of carbon dioxide concentrations are un- 
related to their initial values yo9;, but are determined only by the 
Sarameters of the closed ecological system. If the second mode I>, is 

inthe dark, the concentration of CO2g in the general collector is determined 
Sy the equation: 


90 











Let us now turn to determination of mean stationary values of oxygen 
concentration, xj (i = 1, n). 


In che general case, systems (la) and (1b) [1] must be solved together. 


However, if the concentration of carbon dioxide is close to its mean 
stationary level, i.e., conditions (3b) [1] are virtually met, one can 
use the following approach. 


Accotding to eiai‘on (la) [1], the concentration of oxygen in compartments 
can be estad «iv only after the concentration of carbon dioxide in them 
is establishei. For this reason, in order to deti.rmine the stationary 
concentrations of oxygen we shall examine equation (la) [1] with already 
stationary levels of carbon dioxide. 


Adding up the (la) [1] for all "i" and considering the conditions of 
stability (3a) [1], we shall obtain: 


tence: 
n 4 
v Wik; s W, Xj ~ const 
i j ‘ l 
and 
S - 
v v, (x, — Ses) - 0, (8) 


i=] 
-_-_ 


where x 4 refers to initial conditions for oxygen concentrations 
in inhabited compartments. 


We have from equation (3a) [1]: 





V.( y) > Vx, tel 2 
ae A =I,an- 
Q Q-w; 
Therefore, we can write down: 
- Vx, a Vy - Vy 
x, 4 =X,+ = + A. , 
Q-w, , QW, ™ Q-@, ” 


By solving equations (8) and (9) together, we obtain the equa- 
tions for determination of stationary values: 


“ I 4 V ; 
Vwi gS ( Ys1— Yet |v, 


a= n : ’ (10) 





91 








We see from equation (10) that the stationary concentrations of oxygen x; 
depend on the initial conditions. 


Thus, with 7 = 1, the mean stable concentration x) will be its initial 
level, xoi. With ”>2, the stable concentrations xj will be different from 
their initial values in the general case. 


Let us mention that the results obtained above for = 1 are entirely con- 
sistent with the conclusions in [2], in which a system with one compartment 
is studied. 


First example: Let us consider an ecological system, closed with regard 
to exchange of gases, with one habitable compartment and an autotrophic 
component that operates in light and darkness, with the following para- 
meters corresponding to the data submitted in [2]: 


V,,= 0,012 3h; VE! = 0,0625 m°/h; rt = 0,85; 
r°? 4; vi? —0,0074 wh; V)' = 0,0531 m*h; 
vo? = —0,0074 m¥/h; W = 20 mw; T, = 23h. 


in order to satisfy the necessary and sufficient conditions for stability 
of a closed ecological system, let us take ('.82 as the coefficient of 
respiration of the heterotrophic components [3]. Then the rate of 0, 
uptake by the heterotrophic components will be Vy, = 0.0146 m°/h. For 

this system, we have to define the parameters of programmed control that 
would provide for stable, periodic changes in concentrations of 0, and CO, 
as well as the mean stable value for CO>. 


The control parameters T,; and T2, which were calculated using formulas (1) 
and (2) constitute 14.7 and 8.3 h, respectively. 


fhe meen stationary value of C02 is 0.682. 


For the sake of comparison, let us mention that the values for control 
parameters defined in [2] are very close to the ones we calculated, 
constituting T; = 15 h and T> = 8 h. 


Second example: Let us consider an ecological system with two habitable 
compartments and the same autotrophic component as in the first example, 
which operates in the light and darkness, with the following parameters: 
V,, = 0,004 43 /h, Vz, = 0,008 wh V) = 0.00328 wh: V) = 0.00656 x?/h; 
v2! -- 0,0625 w?/h; V2? = —0,0074 wt/h; V9! = 0.0531 wh; vy == 0.0074 wh; 
VW, = 5 Wy = 15 M8; w, = 0,333; wy ~ 0,667; Xo, = 21.5%: Fog = 21%; 
Yor -_ 08%; Yor = 0.3%; T. 2 h. 


92 








We need to calculate the program for control of the autotrophic component. 


Accordiug to (10), the stationary values for oxygen, xi and x2, are the 
same and equal 21.1252. 











xt). % a b 
08s 24 
} vr! ¢) 
z. (et) a4 
220° 
| 151 ‘ 
| MSN 5/t) Ble) 








0 © © 60 50 Stmingd 0 © © SO St min 


Concentrations of carbon dioxide yi(t) and y2(t) (a) and oxygen 
x, (t) and x2(t) (b) as a function of time after turning on the 
programmed control system 


The stationary values for carbon dioxide (7) are yi = y2 = 0.68%. 


Taking into consideration formula (1), operating time in mode [2 is 
T2= 0.716 h, and in mode I; T; = 1.284 h. 


The Figure illustrates the curves of changes in oxygen and carbon dioxide 
concentrations after turning on the system of programmed control. 


BIBLIOGRAPHY 


l. Nasonov, A. S., and Toroptsev, V. S. KOSMICHESKAYA BIOL. [Space 
Biology], No 6, 1979, pp 63-68. 


2. Shabel'nikov, V. G. Ibid, No 6, 1975, pp 36-40. 


3. Smirnov, I. V. in "Problemy kosmicheskoy biologii" [Problems of Space 
Biology], Moscow, Vol 19, 1972, pp 90-180. 


93 














UDC; 612.858.2/.,5+612.886] .014.46:546. 33 


EFFECT OF SODIUM BICARBONATE ON REAC:IVITY AND TROPHICS OF VESTIBULAR 
ANALYZER 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 64-68 


[Article by N. I. Arlashchenko, submitted 20 Jan 77] 


{English abstract from source] 


Prevention of motion sickness by intravenous injections of sedium plenroenine Gane 
direct result of trophic changes or effect of the chemical on the functional activity 


pe a 
[ entral termations 


[Text] Hasegawa was the first to demonstrate on rabbits and man [1], in 
1949, that sodium bicarbonate prevents signs of motion sickness when 
injected intravenously to animals and man; this was confirmed in subse- 
quent studies [2-4]. However, the mechanism of preventive action of 
sodium bicarbonate is not clear to this day. At any rate, dissolution 
of otoliths in the labyrinthine vestibulum, as assumed by Hasegawa [2], 
does not occur, and this was proven [5] by means of an original tech- 
nique for making a preparation of the vestibular system, which precludes 
the use of decalcification, which is inevitable with the usual techniques 
for making preparations of the inner ear [6]. Perhaps, depression of 
autonomic reactions occurs as a result of elevation of threshold of 
stimulation of chemoreceptors of the trigger zone in the vomiting center, 
demonstrable by the increase in threshold of apomorphine vomiting in dogs 
after administration of sodium bicarbonate [7]. Some authors [4] believe 
that prevention of signs of motion sickness (nausea, vomiting, hyper- 
hidrosis and other manifestations of motion sickness) after administra- 
tion of sodium bicarbonate is attributable to normalization of hemodynamics, 
increase in alkaline reserve of blood and improved tissular oxygenation. 


Our objective here was to study the mechanism of the effect of sodium 
bicarbonate on the vestibular analyzer. 


94 











Methods 


The presence of a barrier mechanism in the inner ear, which provides for 
relative stability of chemical composition of labyrinthine fluid, has 
been proven by several researchers, who observed limited penetration 

of various dyes and radioactive tracers from blood into the lymph of 

the ear [8-9]. Experiments on dogs and cats [8] proved that such 
specialized vasotissular barriers as the hematolabyrinthine (HLB), 
hematoophthalmic (HOB) and hematoencephalic (HEB) barriers are equally 
permeable to labeled phosphorus. Experiments on rabbits [9] established 
that there is equally limited permeability of the same barriers for 
fluorescein. As a rule, studies of barrier function of the HLB are 
conducted in the form of acute experiments, with collection of perilymph 
from the labyrinth. For this reason, we tested permeability of the HOB as 
a model that would enable us to make a judgment about disturbances in 
permeability of specialized vasotissular barriers in the course of a 
chronic experiment. The transparency of the internal media of the eye 
makes it possible to directly observe and objectively record penetration 
of intravenously injected fluorescein (0.5 cc 5% solution per kg weight) 
into the lymph of the anterior chamber of the eye. The intensity of 
fluorescence of fluorescein in the humor of the chamber was measured in 
relative units with a luminescence microphotometer for 3.5 h after in- 
jection of the dye [10]. In our experiments, permeability of the HOB in 
rabbits examined under normal conditions and 2 h after total-body y- 
irradiation from a cesium source, in a dose of 700 R at the rate of 

37 R/min, served as an indicator of normal "physiologically adequate" 
[11] and pathological “physiologically inadequate" permeability of the 
vasotissular barrier. We gave the rabbits intramuscular injections of 
ethaperazine, in a dosage of 1 mg/kg weight, 10-15 min prior to exposure 
to radiation, in order to determine the nature of changes in permeability 
of the vasotissular barrier under the influence of factors aimed at the 
reticular formation. 


We tested vestibular function by means of a VU-2 type device [12] with an 
electronic control console. We rated the hystagmic and respiratory reac- 
tions to stop stimuli of 5, 7, 10, 2C, 30, 40, 60 and 90° per second, 

in several background studies and 20-30 min after intravenous injection of 
sodium bicarbonate (15 m& 5% solution). After this, to enhance the 
quality of histological treatment and demonstration of early morphological 
changes in the labyrinth, we performed in vivo fixation of the labyrinths 
based on replacement of the animal's blood with Vitmak fluid. The 
temporal bones with fixed labyrinths were extracted from the skull and 
submitted to histological treatment (fixation in Vitmak fluid for 3 weeks 
at a temperature of 37°C, decalcification in 5% nitric acid solution to a 
specific degree of softening, neutralization in 10% sodium sulfate, 
flushing, dehydration in alcohols, embedding in celloidin, preparation of 
serial sections and staining thereof with hematoxylin-eosin). 


95 








Figure 1. Histology of the labyrinth after intravenous injection 
of sodium bicarbonate. We see the collapse of the walls 
of the membranous labyrinth (n) on the level of the 

utricular sac (y) and ampulla of the semicircular duct (a). 

Normally, the membranous labyrinth has the same shape as the 

osseous (k); hematoxylin-eosin stain; magnification 3,5*7 


ak) ampullar crista ym) utricular macula 


In all, we used 42 rabbits in different series of experiments. The data 
obtained in the experiments were submitted to statistical processing. 


Results and Discussion 


The morphology of the inner ear after injection of sodium bicarbonate 
(Figure 1) indicates that there is some degree of compression of the menm- 
brano.s labyrinth, collapse of the walls of the utricular sac so that they 
are in contact with the sensory receptor epithelium of the crista. 


Figure 2 illustrates the levels of normal permeability of the HOB before 
and after injection of sodium bicarbonate and pathological permeability of 


96 











the vasotissular barrier as a result of exposure to ionizing radiation. 
Injection of sodium bicarbonate 10-15 min before irradiation altered the 
Signs of radiation destruction of the vasotissular barrier, leading to 
slower migration of fluorescein into the humor of the chamber. Delayed 
passage of the tracer into the lymph of the anterior chamber of the eye 
was also observed when the animals were given ethaperazine 10-15 min 
before irradiation. 


Depression of the @ystagmic reac- 














ps | tion was somewhat more marked 
wor | after administration of sodium 
ISO bicarbonate than as a result of 
a conditioning by means of back- 
130+ ground rotation. Processing by 
asl \ the differential method revealed 
| TN reliable differences in reactions 
to stop stimuli of 30, 40 and 90° 
| 4 per second before and after admi- 
ZL 3 nistration of sodium bicarbonate. 
y There were also appreciable 
§ changes in respiration reaction 
| to stop stimuli of 40, 60 and 90° 








per second under the influence of 
sodium bicarbonate (see Table). 


It can be assumed that the endo- 
lymph is a nutrient medium for 
labyrinthine receptors, since the 
5 latter have no direct contact with 
10 30 60 90 120 150 WO the system of blood vessels [13]. 
. Fer this reasor, the slightest 
change in electrolyte composition 








Figure 2. of ear lymph, due to impairment 
Permeability of HOB for intravenously of the vasotissular barrier, 
injected fluorescein. X-axis, time should affect the function of ves- 
after injection of fluorescein (min); tibular receptors. The possibility 
y-axis, intensity of fluorescence of of using HOB indices to test the 
fluorescein in chamber humor (in barrier function of the HLB is based 
relative units) on the coincidence of levels of 
1) normal permeability of both vasotissular 
2) against the background of sodium barriers to intravenously injected 
bicarbonate fluorescein [8, 9]. Penetration of 
3) 2 h after irradiation fluorescein and sodium salt of 
4) after irradiation, against the fluoresceinic acid is indicative 
background of sodium bicarbonate also of the possibility of passage 
5) after irradiation, against the through vasotissular barriers of 
background of ethaperazine very small amounts of other sodium 


salts under normal conditions, 
including sodium bicarbonate. 





97 














Respiratory reaction to stop stimuli (10-s interval) in background 
studies and 20-30 min after injection of sodium bicarbonate (% of 
number of respiratory excursions before stop stimulus) 








Magnitude of stop stimulus, degrees/s 
Nature of rotation —— — 





20 30 40 f0 90 | $20 
| | 
Background, first | 101+2) 190+2 e+! | $8+-3 | ac+?2 | &e+8 
Background, second; 100+! | WG+? 92-4 | S84 | Ra+4 0 | O11 
Background, third | 100+! | i0i1+2 Ga+}3 9e+3 192+5 | 109+6 
After injection of 


sodium bicarb. | 99+7 1084-4 12i+5 | 12847 | «612147 | ll 
| | 





The endclymph has the same proportion of electrolytes as intracellular 
fluid, in particular, there is an exceptionally high potassium content. 
The perilymph, in which there is prevalence of sodium ions, is closer to 
blood in composition of electrolytes. For this reason, the appearance of 
an excess of sodium cations in perilymph after administration of sodium 
bicarbonate could increase eiflux of fluid and endolymph, and it could 
lead to elevation of OSmotic pressure of perilymph and compression of the 
membranous labyrinth. Evidently, compression of the latter after intra- 
venous injection of sodium bicarbonate is indicative of normally present 
osmotic equilibrium of endolymph and perilymph. We observed even more 
marked compression of the membraneous labyrinth after exposure of animals 
to total-body ‘radiation [14]. It is known that ionizing radiation 
destroys specialized vasotissular barriers [15-17]. Along with drastic 
increase in permeability of the vasotissular barrier, which is observed 

2 h after exposure to ionizing radiation [18, 19], there are also marked 
changes in excitability and reactivity of the vestibular analyzer, as 
manifested by elevztion of threshold of ,erception of angular accelera- 
tions, attenuation and rec :ction of duration of nystagmic reaction to 
stop stimuli [20-22]. Eviuently, both a change in electrolyte composition 
of ear lymph and a change in intralabyrinthine pressure of liquid media, 
which occurs as a result of impairment of the HLB, may be the source of 
peripheral afferent influences capable of altering the sensitivity of the 
vestibular analyzer to vestibular stimuli. It is also possible that 
these trophic disorders attenuate the vegetovestibular manifestations of 
motion sickness under the influence of sodium bicarbonate. 


The change in nature of radiation damage to the vasotissular barrier 

against the background of sodium bicarbonate is manifested by slower 

passage of the dye into the humor of the chamber, appearance of a "flat" 
curve of dynamics of pathological permeability of the vascular barrier. 
Preliminary administration of ethaperazine had exactly the same effect on 
the nature of pathologically increased permeability of the vascular 

barrier with exposure to radiation. In view of the fact that ethaperazine 
affects the same structures of the central nervous system as aminazine [23], 


98 





and in view of the fact that the shape of the curves of pathological per- 
meability was the same under the influence of sodium bicarbonate and etha- 
perazine, it may be assumed that sodium bicarbonate influences the func- 
tional state of the brain stem. In particular, the shift of blood pH as 

a result of administration of large amounts of anion of carbonic acid, as 
indirectly indicated by changes in the respiratory reaction to stop scimuli 
after injection of sodium bicarbonate, could be the active factor. Evi- 
dently, tue so-called extralabyrinthine nature of effect of sodium bicar- 
bonate on the vestibular analyzer consists of the above mediated influence 
on the central stem formations of the nervous system. 


Thus, as a result of these experiments, it was established that intra- 
venous injection of sodium bicarbonate has an appreciable effect on func- 
tional activity of the vestibular analyzer, attenuating nystagmic and 
distorting respiratory reactions to stop stimuli. On the basis of the 
obtained deta, it can be assumed that, when injected intravenously, sodium 
bicarbonate influences primarily the liquid media of the labyrinth, dis- 
rupting osmotic equilibrium of endolymph and perilymph, and leading in 
some cases to compression of the membranous labyrinth. Aside from its 
direct effect on labyrinthine trophics, sodium bicarbonate also affects 
the body via the vegetative centers, as indicated by the analogy of 
effects of pathologically increased permeability of the vasotissular 
barrier after administration of sodium bicarbonate and ethaperazine. Thus, 
the changes in vestibulosomatic and vestibulovegetative reactions to stop 
stimuli, which occur after intravenous injection of sodium bicarbonate, 
could be the result of both the direct trophic influence on the peripheral 
part of the vestibular analyzer and the extralabyrinthine effect via the 
higher vegetative centers. The described mechanisms probably explain the 
distinctions of the effect of sodium bicarbonate on vestibulovegetative 
manifestations of motion sickness. 


BIBLIOGRAPHY 
1, Nasegawa, T. ARCH. OTOLARYNG., Vol 50, 1949, p 708. 


Be Idem, ARCH. OHR.-NAS. U. aCHLK.-, HEILK., Vol 166, 1955, Pp 319, 


3. Barnatskiy, V. N., and Kuznetsov, A. G. KOSMICHESKAYA BIOL. [Space 
Biology], No 1, 1968, p 49. 


4, Barnatskiy, V. N.; Bryanov, 1. I.; Volosevich, R. M.; et al. Ibid, 
No 6, 1972, p 70. 


5. Vinnikov, Ya. A.; Lukashevich, T. T.; and Zhinkin, I. L. VESTN. 
OTORINOLAR. [Vestnik of Otorhinolaryngology], No 5, 1964, p 72. 


6. Vinnikov, Ya. A., and Titova, L. K. ARKH. ANAT. [Archives of 
Anatomy], No 4, 1959, p 82. 


99 

















ll. 


23. 





Syabro, 0. I. “Studies of Pharmacology of Antiemetics,™ author 
abstract of doctoral dissertation, Leningrad, 1965. 


Zayko, N. N. DOKL. AN SSSR [Reports of the USSR Academy of Sciences], 
Vol 102, No 4, 1955, p 831. 


Yershov, V.I. TRUDY VOYEN.-MORSK. MED. AKAD. [Works of the Naval 
Medical Academy], Vol 34, 1952, p 36. 


Gromov, V. A., and Nakhil'nitskaya, Z. N. in "Sbornik referatov po 
radiatsionnoy meditsine za 1958 god" [Collection of Abstracts on 
Radiation Medicine for 1958], Moscow, 1959, p 154. 

Rosin, A. Ya. in "Fiziologiya i patologiya gistogematicheskikh 
bar'yerov" [Physiology and Pathology of Blood-Tissue Barriers], Moscow, 
1968, p 10. 


Grigor'yev, Yu. G., and Bokhov, B. B. VESTN. OTORINOLAR., No 6, 
1961, p 85. 


Mayerovich, I. M. "The Hematolabyrinthine Barrier,” Leningrad, 1973. 


Shikhodyrov, V. V.; Arlashchenko, N. I.; and Grigor’yev, Yu. G. 
RADIOBLOLOGIYA [Radiobiology], No 4, 1971, p 560. 


Kiselev, P. N. “Effect of X-Rays on Permeability and Barrier Func- 
tions of Body Tissues," author abstract of doctoral dissertation, 
Leningrad, 1951. 


Shtern, L. S.; Rapoport, S. Ya.; Gromakowskaya, M. M.; et al. 
BIOFIZIKA [Biophysics], No 2, 1957, p 18/7. 


Kassil', G. %. “The Hematoencephalic Barrier," Moscow, 1963. 


Arlashchenko, N. I. MED. RADIOL. [Medical Radiology], No 3, 1956, 
p 29. 


Idem, OFTAL'MOL. ZH. [Ophthalmological Journal], No 4, 1961, p 233. 
Sveshnikov, A. A. MED. RADIOL., No 9, 1963, p 48. 


Sevan'kayev, A. V. in “Aviatsionnaya i kosmicheskaya meditsina”™ 
[Aviation and Space Medicine], Moscow, 1963, p 431. 


Grigor'vev, Yu. G.; Farber, Yu. V.; and Volokhova, N. A. "Vestibular 
Reactions,” Moscow, 1970. 


Mashkovskiy, M. D. "Drug Products,” Moscow, 8th edition, Vol 1, 1977, 
p Sl. 


100 




















CLINICAL STUDIES 
UDC: 616.85-057:613,693] 650, 311.44 


EVALUATION AND FORECASTING OF MENTAL FITNESS OF FLIGHT PERSONNEL IN THE 
PRESENCE OF NEUROSIS 


Moscow KOSMICHESKAYA BIOLOGIYA I ..VIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 68-72 


[Article by K. K. Ioseliani, submitted 23 Jan 78] 


{English abstract from source] 


Features of psychic functions and mental performance of flight personnel sufier- 
ing irom various neuroses were examined by clinical and psychological methods The 
Most severe and persistent changes in mental performance were found in neurasthenics. 
Higher mental productivity was detected in 80 % of subjects with other neuroses (neuro- 
tnx states and reactions, asthenic state, emotional-vegetative instability) (P<0.00))- 
These findings can be regarded as important diagnostic and prognostic criteria e\per- 
tise and performance evaluations 


[Text] Adverse flight factors lead, in some cases, to disruption of the 
correlation between excitatory and inhibitory processes in the central 
nervous system (CNS) and are instrumental in development of neurosis [1]. 

A number of Soviet researchers [1-4] have reported that in 40-50% of 

the cases development of neurosis among flight personnel is related to the 
most dangerous and stressful segments of flight (worsening of well-being, 
illusions, accident situations, erroneous actions, loss of spatial orienta- 
tion, etc.). Some of the characterological personality traits (impression- 
ability, anxiety, accentuated self-confidence, stubornness), which prevent 
overcoming difficulties and complicate vital situations are also instru- 
mental in development of neurosis [5-8]. 





There has been no general recognition of methods of clinicopsychological 
testing (CPT) in diagnostics and expert evaluation of fitness for work 

in the presence of neurosis, and in some cases they are even disputed, 
although prominent specialists in medical psychology believe that they 
can be used to obtain important information that supplements the findings 
of clinical examination [5, 9, 10]. 


101 








In the last few years, psychologists, psychoneurologists and psychiatrists 
have shown great interest in personality tests and questionnaires that 
have been adopted from foreign practice [1l, 12]. However, it is difficult 
to use these tests, since each of them involves a certain system for 
interpreting the results, which bears the influence of the conceptions 

of personality that are developed by their authors. Moreover, the 
existing level of the technique for interpretation of results does not 
assure adequate reliability of conclusions and total independence thererf 
from the experimenters [9]. 


In our opinion, the methods of clinicopsychological testing,* which 

make it possible to demonstrate the structure, nature and extent of mental 
disturbances, individual psychological distinctions and functional capabi- 
lity of flight personnel under model conditions, best meet the pressing 
need for psychological determination of fitness in the presence of 
neurosis for purposes of expert medical flight certification (EMFC). 


Neuroses are in first place among all diseases of the nervous system in 
flight personnel, and they are the most frequent cause of occupational 
disqualification [1-4, 13]. For this reason, it is an important task 

for psychologists and expert neuropathologists to study the nature of 
functional disturbances in these individuals (including mental functions, 
fitness for work and behavioral reactions) in order to predict professional 
reliability. 


It should be noted that the early stages of functional diseases of the CNS 
are seldom associated with marked impairment of mental fitness, and this 
is what causes difficulties in diagnosing them and making an expert 
judgment [1, 14]. Im such cases, the results of CPT could play an import- 
ant role as a diagnostic and prognostic criterion of performance reserve 
of flight personnel. 


We failed to encounter such data about flight personnel in the available 
literature, and this served as grounds to conduct special stud‘es in this 
direction. 


In this work, we submit the results of our study of the dynamics and struc- 
ture of the main mental functions and mental fitness of flight personnel 
suffering from neurosis, for the purpose of predicting professional 
reliability. 





*In essence, psychological examination of flight personnel for EMFC pur- 
poses is also the content of clinicopsychological examinations, since 
they constitute one of the components of a comprehensive work-up that 
is conducted for diagnostic and expert certification purposes. 














Methods 


We used the following techniques: “continuous counting in a specified 
tempo” to test emotional stability during performance; “retrieval of 
numbers, with switch-overs” (modification of F. D. Gorbov [2]) to test 
noise stability [resistance to interfer:nces] during performance of 
differentiated, complex activity; "determination of patterns" to test 

some aspects of thinking (sharpness, activity and flexibility of thinking, 
critical attitude, capacity to establish consistent correlations, etc.); 
“compasses” for testing reproductive thinking and capacity to operate 
with spatial conceptions; “text reproduction" to test logical memory. 

This route of examination of individual psychological distinctions of j 
the pilot's personality, which is being developed primarily by aviation 
psychologists [1, 2, 13, 14], is based on creating a model situation 

that reproduces different aspects of the difficult conditions of flight 
work. 


The conclusion about the fitness level (high, average, low) was made only 
after summarizing the results of all of the methods used according to 
specially developed criteria on a 9-point scale [14]. 


A total of 100 people (81 pilots and 19 navigators) were submitted to 
the testing; they had been referred for in-hospital examination and 
to settle a question of expertise due to diminished performance, 
fatigability during flights, irritability, sleep disorders, depressed 
affect, pain in various organs, etc. For the sake of comparison and 
analysis of CPT results, we also examined essentially healthy flight 
personne! (100 people) who made up the control group. 


Results and Discussion 


Experimental data obtained on the control group served as the base cri- 
terion in analyzing the CPT results. 


The control group of subjects gave the impression of being collected, 
concentrated and sharp [quick-witted] people (88 of them had a high 

level of performance and 12 an average level). Yheir mental fitness was 
characterized by the following features: high initial readiness, manifested 
by good productivity at the first stage of a long work period; rapid adjust- 
ment, manifested by finding an adequate work procedure; transition from 

the elementary stage of coping exogenously specified rules to interiorized 
procedures, rapid development and readjustment of mental work skills; 
uniformity and stability of rate and rhythm of performance; commensurate 
interaction of voluntary and automated elements of performance and ade- 
quate change in procedures; smooth change from visual to mental level 

of performance and use of the latter as the refined work procedure; 
creative thinking; clearcut performance of intensive mental work when 

there is a shortage of time and exposure to informational interference; 


103 








fine differenriation of performance at the difficult stages of an assign- 
ment; critical attitude; insignificant (latent) manifestation of fatigue 
at the end of a long work period. 


As a result of the comprehensive (clinical, instrument and clinicopsycho- 
logical) examination of individuals in the main group, the following forms 
of neurosis were diagnosed: neurasthenia in 55 cases; neurotic states 

and reactions in 16; asthenic state fn 10 and emotional vegetative 
instability in 19 people. 


In order to graphically follow some of the distinctions and relationship 
between changes in mental functions and “itness for work occurring in 
recponse to various forms of neurosis, and for the sake of convenience in 
comparing these changes, it is deemed expedient to consider them in two 
subgroups differing in findings: the first subgroup consisted of indi- 
viduals suffering from neurasthenia (55 people) and the second, all 

the rest of the individuals in the main group (45). 


The patients in the first subgroup were characterized by marked emotional 
instability, conflict, exhaustibility, fixation on their sensations, 
depressed affect, sleep and memory disorders. There was a significant 
decline in mental work fiinecs. Of this subgroup, ~/ people had difficulty 


in performing their ass snuents throughout the work period; they also 
made mistakes, particu! rly when there was a shortage of time and when 
switching to the opposite mode of work. Marked exhaustibility of mental 


functions, lack of the necessary readiness for performance of current work 
and disorganization of mental activities were found in 28 individuals, 
who scored the lowest in performance. In view of the severe worsening 

of well-being, 19 people had to stop ihe work. They usually stopped 
working after the work rate slowed down and number of mistakes, which 
became more and more flagrant, increased. Some subjects developed 
distinctive nwmory "lapses" (they forgot the instructions to follow in 
their work, current result of counting, direction [sign] of action, etc.) 
when there was a tight schedule. This was indicative of marked impair- 
ment of the elements of the complex functional structure that are usually 
related to phenomena referable to immediate recall [operative memory]. 
During complex differentiated activity ("retrieving numbers with switch- 
overs") there was more frequent perseveration, impairment of color 
differentiation and significant divergence of series. Impairment of cog- 
nitive processes was noted in the "compass" and “establishment of 
patterns” tests. 


All 55 subjects in the lst subgroup were deemed unfit for flight work by 
the VLK [medical commission for determination of tiight fitness]. 


The second subgroup of subjects was characterized by some emotional insta- : 
bility, increased fatigability and perspiration, superficial sleep. } 
Against the background oi an uneven work pace, moderate nervous tension 


104 








and heightened emotional reaction to an experimental situation (facial 
vasomotor activity, systemic and palmar hyperhidrosis, faster pulse, etc.), 
the subjects presented much better results in the CPT for mental fitness 
than the first subgroup (see Table). After generalization of the obtained 
data, it was established that 19 people had a high score, 21 average and 

5 low. The individuals in this subgroup were characterized by rather 

high degree of conditioning, which was indicative of structural integrity 
of their mental performance. It should be noted that the rather high 
productivity of these individuals was achieved at the price of enlisting 
their internal reserves. 


Comparative CPT results for individuals in the lst and 2d subgroups 




















| Performance level, % 
Subgroup _ Number of subjects | High Average Low 
} 
First 55 -- 49+9.5 51*9.5 
Second 45 42+11.3 47+10.9 11*10.3 
- 1 LL 
Totals 100 19*7.2 48+7.2 3328.1 





Note: Reliability of differences between performance rating 
for subjects in first and second subgroups with P<0.01. 


The individuals in the main group, who suffered from neurosis, presented 
a statistically reliable discrepancy in mean performance scores (P<0.001), 
as compared to the control group. 


The CPT results, along with the clinical findings and results of other 
functional load tests, made it possible to resolve the expert question in 
the affirmative in 31 cases, deeming subjects to be conditionally fit for 
flight work, thereby retaining personnel for aviation. In 69 cases the 
expert judgment was negative (see Table). 


It is important to note that ell of tae 33 individuals who had low scores 
in the CPT were deemed unfit for flight work, while all 19 who had high 
performance scores were allowed to continue with their flying activities, 
although there were some restrictions. 


These studies revealed that CPT methods m'‘.e it possible to determine the 
correlation between efficiency of solving psychological problems, on the 
one hand, and clinical manifestation of disease, on the other. This 
enables us to assess the obtained indices as important diagnostic and 
prognostic criteria of professional fitness of flight personnel. This 

set of methodological procedures may aid in more differentiated evalua- 
tion of the severity of neurosis, with respect to conformity of the 
psychological and functional capabilities of a pilot with the requirements 
stipulated by the VLK. 


105 











BIBLIOGRAPHY 
Gorbov, F. D. in "“Obshchestvo psikhologov SSSR. S"yezd 3-y. 
Materialy" [Society of USSR Psychologists, Proceedings of 3d Congress], 
Moscow, Vol 3, Vyp 1, 1968, pr 115-117. 


Idem, in “Inzhenernaya psikhologiya” [Engineering Psychology], Moscow, 
1964, pp 340-357. 


Mishurin, V. M. VOYEN.-MED. ZH. [Military Medical Journal], No 2, 
1959, pp 62-67. 


Severskiy, A. I. "Treatment and Prevention of Neurosis Among Flight 
Personnel,” Moscow, 1965. 


Myasishchev, V. N. “Current Conceptions of Neuroses," Moscow, 1956. 
Davidenkov, S. N. "“Neuroses," Leningrad, 1963. 

Bamdas, B. S. “Asthenic States," Moscow, 1941. 

Svyadoshch, A. M. “Neuroses and Their Treatment," Moscow, 1959. 
Karvasarskiy, B. D., and lovlev, B. V. in “Kliniko-psikhologicheskiye 
issledovaniya iichnosti (v svyazi s zadachami profilaktiki, 
diagnostiki i lecheniya nervno-psikhicheskikh zabolevaniy)" [Clinico- 
Psychological Personality Tests (Related to Prevention, Diagnosis 

and Treatment of Mental Diseases)], Leningrad, 1971, pp 43-47. 
Tonkonogiy, I. M. Ibid, pp 72-75. 

Karandasheva, E. A., and Kister, T. P. Ibid, pp 150-153. 
Dneprovskaya, S. V. Ibid, pp 116-119. 

Platonov, K. K. "Psychology of Flight Work," Moscow, 1960. 
Iloseliani, K. K. "Clinico-Psychological Tests in the Practice of 


Medical Flight Expertise," author abstract of doctoral dissertation, 
Moscow, 1975. 


106 

















BRIEF REPORTS 
UDC: 616-092.9-02:612.766.2 


DYNAMICS OF STRESS REACTION OF RATS DURING EXPERIMENTAL HYPOKINESIA 
VARYING IN DURATION, AND POSSIBILITY OF CORRECTION THEREOF 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 72-74 


{Article by L. Y. Kirichek, submitted 12 Jun 78] 


[Text] It is known that, along with other factors, prolonged restriction 
of muscular activity plays an important role in development of the hypo- 
kinetic syndrome [1-3]. There are indications in the literature that 
hypokinesia first leads to a stress reaction, which is then followed by 

a period of adaptation, after which a state develops that characterizes 
the effect of hypokinesia as such [4-7]. 


Our objective here was to track the dyramic intensity of the stress 
reaction in rats as a function of time of restriction of movement, to 
determine the tice of maximum manifestation of stress and demonstrate 
the nature of change therein under the influence of some central neuro- 
tropic agents. 


Methods 


Experiments were conducted on 210 mongrel white rats of both sexes, with 
an initial weight of 100 to 200 g, which were separated into groups of 6 
animals. Hypokinesia was produced by means of special box cages made of 
plexiglas, which drastically restricted movement, but did not make 
routine care of the animals difficult. All of the animals were fed the 
same diet and maintained under the natural conditions of day and night. 
Hypokinesia lasted for 1 to 24 h and 1 to 30 days, with recording of 
parameters every hour for the first 6 h, then 12 and 24 h for the first 
3 days of the experiment, on the 5th, 7th and 19th days, and every 5 
experimental days thereafter. The weight coefficients of the thymus and 
adrenals, ascorbic acid content of the adrenals [8], blood eosinophils, 
incidence and intensity of onset of an ulcerative process in the stomach 
[9]. In addition, we recorded the rats’ weight before and after hypo- 
kinesia, as well as death rate. Vivarium animals (20 rats in a cage with 
a 45x45 cm* floor) served as a control. We used psychotropic depressants 





107 











as products for pharmacological correction of stress: reserpine (1-2.5- 

5 mg/kg by mouth) and amizil (1-2.5-5 mg/kg by hypodermic injection), 
which were given once 2 h before the end of the period of hypokinesia 

and repeatedly over a 10-day period, 5 days before hypokinesia and for 

the entire period of hypokinesia (5 days). In this series of experiments, 
rats given isotonic solution of sodium chloride under analogous conditions 
served as a control. We used the parametric method of Student for sta- 


tistical processing of digital data. 





Results and Discussion 


The obtained data revealed that hypokinesia induced changes characterizing 
development of stress in the rats. This was manifested by a decrease in 
weight coefficient of the thymus, hypertrophy of the adrenals, undulant 
changes in ascorbic acid level in the adrenals, decrease in blood eosino- 
phils and appearance of trophic disturbances of the gastric mucosa, the 
incidence and severity of which also fluctuated. The severity of changes 
was dissimilar as a function of time for each of the parameters studied. 
First to change, after exposure for 1 h, was the adrenal ascorbic acid 

levei, which declined. Subsequent changes in level thereof were 

phasic and reflected fluctuation of functional activity of the adrenals 

in the course of the entire experiment. Adrenal weight increased after 

24 h of hypokinesia and then increased consistently up to the 15th day, 

after which it became stable. In the interval between the 2d h and 15th 

day of hypokinesia, there was a decline of weight coeffficient of the 

thymus. After the 15th day, this parameter increased and even exceeded 

the mean base level by the end of the experiment. On the 5th day of hypo- 

kinesia, there was a decrease in eosinophils, then their number began to 

grow again, and by the 30th experimental day it was double the control 

level. The trophic disturbances appeared early (after 1 h of hypokinesia) 

in the gastric mucosa, and they were manifested at first only by pallor 

and edema of the mucosa, distension and atonia of th gastric walls. 

Effusions of blood, erosions and ulcers appeared inthe rat stomach after 

12 h of hypokinesia and reached a maximum (mean grade of 2) on the 5th, 

15th and 20th days. A comparison of the dynamics of all parameters studied 

revealed that the maximum changes were referable to the period between the 

5th and 15th days of hypokinesia, after which restoration of parameters 

began. Accordingly, there was also a change in weight of the animals 

at these times: 19 and 18% drop, as compared to base levels, at first 

and then restoration toward the end of the experiment. There were no 

deaths of animals. 





The experiments involving the use of drugs were conducted against the 
background of 5-day hypokinesia. Under these conditions, a single in- 
dose of reserpine enhanced the stress reaction, leading to more marked 
adrenal hypertrophy, even greater drop in adrenal ascorbic acid and blood 
eosinophil content, and increase in incidence of ulcers in the stomach. 
With the second intake of reserpine, this influence was less marked, or 


108 











even combined with a decline of eosinopenia. The effect of amizil was 
manifested only when it was given repeatedly, and it was characterized 
by prevalence of attenuating influence on intensity of stress reaction 
indices. This was indicated by an increase in weight coefficient of the 
thymus, decline in adrenal ascorbic acid content, less marked decline of 
blood eosinophils and considerable drop in incidence of gastric ulcers. 


Analysis of the obtained data and comparison thereof to those in the 
literature [10-13] revealed that the model of experimental hypokinesia 
that we used induced a stress reaction in rats, the manifestations of 
which were consistent, interrelated, synchronous and characterized by 

the presence of stages. The anxiety stage under such conditions had 

two waves of manifestation, in the first 5-6 h and on the 5th-15th days, 
which corresponds to the reactions to stressors described in the presence 
of hypokinesia [14] and two-component stress as the result of primary 
emotional stress and subsequent metabolic effect of restricted movement 
{[10, 12]. On the whole, the time of maximum stress reaction coincided 
with the findings of other authors who studied the dynamics of changes in 
weight of the adrenals and thymus [13-16]. However, according to the 
Same authors, intensification of functional activity of the adrenals 
occurred for the first 5-6 days of hypokinesia, after which there was 
adaptation followed by depletion, in spite of persisting hypertrophy of 
these glands. Evidently, this must be taken into consideration when 
choosing duration of hypokinesia for the purpose of studying the possi- 
bilities of drug correction. The presence of ulcers of the gastric mucosa 
throughout the experiment was indicative of the rather great "hardness" 
of the hypokinesia model we used. The nature of the effects of reserpine 
and amizil, which coincide with data in the literature pertaining to their 
use for other types of stress [17, 18] and used in a number of cases to 
interpret the mechanisms of neurohumoral regulation of the stress reac- 
tion [19], were indicative, on the one hand, of the fact that hypokinesia 
was associated with a stress reaction, the manifestation, course and 
regulation of which are similar to those associated with various extreme 
States and, on the other hand, that it is possible to search for 
protective agents for such conditions among the known agents with central 
neurotropic action (on the example of repeated administration of amizil). 


BIBLIOGRAPHY 


1. Kakurin, L. I. in "Fiziologicheskiye problemy detrenirovannosti™ 
[Physical Problems of Deconditioning], Moscow, 1968, pp 34-43. 


2. Kraus, H., and Raab, W. “Hypokinetic Disease," Springfield, 1961. 


3. Lamb, L. E.; Stevens, P. M.; and Johnson, R. L. AEROSPACE MED., 
Vol 36, 1965, p 755. 


109 











ll. 


12. 


13. 


LS. 


16. 








Dolgun, Z. S.; Novikova, S. P.; and Shashkov, V. S. KOSMICHESKAYA 
BIOL. [Space Biology], No 3, 1971, pp 12-16. 


Tizul, A. Ya.; Sokolov, Ye. I.; Mdinaradze, Yu. S.; et al. SOV. MED. 
[Soviet Medicine], No 7, 1972, pp 147-148. 


Razin, S. N., and Rychko, A. V. VRACH. DELO [Medical Record], No 5, 
1976, pp 104-107. 


Poppay, M.; Gekht, K.; and Morits, V. ZH. VYSSH. NERVN. DEYAT. 
{Journal of Higher Nervous Activity], No 2, 1974, pp 348-349. 


Birch, R. W.; Harris, L. S.; and Ray, S. N. BIOCHEM. J., Vol 27, 
1933, pp 590-594. 


Hillyard, I. W.; Doczi, J.; and Kiernan, P. B. PROC. SOC. EXP. BIOL. 
(New York), Vol 115, 1964, pp 1108-1112. 


Kovalenko, Ye. A.; Popkov, V. L.; and Kondrat'yev, Yu. I. PAT. FIZIOL. 
[Pathological Physioiogy], No 6, 1970, pp 3-9. 


Kovalenko, Ye. A.; Mailyan, E. S.; Popkov, V. L.; et al. USPEKHI 
FIZIOL. NAUK [Advances in Physiological Sciences], No 3, 1975, 
pp 110-136. 


Portugalov, V. V.; Il'ina-Kakuyeva, Ye. I.; Artyukhina, T. V.; et al. 
in “Eksperimental'nyye issledovaniva gipokinezii, izmenennoy gazovoy 
sredy, uskoreniy, peregruzok i drugikh faktorov" [Experimental 
Studies of Hypokinesia, Altered Gas Environment, Accelerations, G 
Forces and Other Factors], Moscow, 1968, pp 29-33. 


Portugalov, V. V.; Il*ina-Kakuyeva, Ye. I.; Rokhlenko, K. D.; et al. 
in "Aviatsionnaya i kosmicheskaya meditsina" [Aviation and Space 
Medicine], Moscow, Vol 2, 1969, pp 163-167. 


Sakharova, I. N. in “Povolzhskaya konf. fiziologov, farmakologov i 
biokhimikov. 4-ya. Materialy" (Proceedings of 4th Povolzh'ye Con- 
ference of Physiologists, Pharmacologists and Biochemists], Saratov, 
Vol 1, 1966, pp 158-160. 


Yurgens, I. L., and Kirillov, 0. I. KOSMICHESKAYA BIOL., No 4, 1972, 
pp 3-6. 


Brekhman, I. I.; Yurgens, I. L.; and Kirillov, 0. I. in "VNII 
fizicheskoy kul'tury. Sektor fiziologii sporta. Materialy za 1966 g." 
[Proceedings for 1966 of the All-Union Scientific Research Institute 

of Physical Culture, Sector for Physiology of Sports], Moscow, 1966, 
pp 15-25. 


110 














17. 


18. 


19. 


Vostrikov, M. S. SBORNIK NAUCH. RABOT VOLGOGRAD. MED. IN-TA 
[Collection of Scientific Papers of Volgograd Medical Institute], 
Vol 26, 1973, pp 153-155. 


Yel'’skiy, V. N. ANEST. I REANIMATOL. [Anesthesiology and Resuscita- 
tion], No 3, 19/7, pp 50-53. 


Shalyapina, V. G. PROBL. ENDOKRINOL. [Problems of Endocrinology], 
No 2, 1970, pp 60-64. 


lll 














UDC: 612,017.1-06:612. 766.2 
EFFECT OF BRIEF ANTIORTHOSTATIC HYPOKINESIA ON BLOOD IMMUNOGLOBULIN CONTENT 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 74-75 


[Article by N. N. Mukhina, V. V. Chestukhin, V. Ye. Katkov and A. P. Karpov, 
submitted 24 May 77] 


[Text] As has been previously shown [1, 2], space flight conditions induce 
a change in immunoglobulin (Ig) levels in peripheral venous blood. In 

this study, we assayed proteins with antibody activity in blood samples 
from different organs, and we tested the effect on levels thereof of brief 
antiorthostatic [head-down] hypokinesia (ANOH), which simulates the acute 
period of adaptation to weightlessness. 


Methods 


Selective catheterization, with collection of blood samples from different 
parts of the cardiovascular system, was performed on male volunteers (6 sub- 
jects) before and after 5-day bed rest in antiorthostatic position, with 
-4,5°tilt of the head end. The subjects were catheterized on a Siemens 
(FRG) unit using two catheters simultaneously, one rigit venous catheter 
(Kurnand No 7) that was introduced after puncturing the ulnar vein into 
vessels of different organs under x-ray monitoring, and a soft arterial 

one that was left permanently in the tfadial artery. 


IgA, IgG and IgM were assayed by the method of Mancini [3], using antisera 
prepared at the Institute of Epidemiology and Microbiology imeni N. F. 
Gamaleya, and the standards of the Behringwerke Firm (FRG). 


The obtained results were submitted to statistical processing by the 
method of pair-by-pair related variants of Student and Fisher, using 
Student's ¢ criterion for statistical analysis. 


Results and Discussion 


Brief hypokinesia induced certain changes in distribution of Ig in the 
blood stream, which was characterized by several distinctions even in the 
hase state (see Table). 


112 



























































Effect of ANOH (bottom row of figures) on Ig content (in mg%) in 
blood samples taken from different parts of the cardiovascular 


system (Mtm) 




















Blood IgA lgG | 1M 

Arterial 357 5+ 38.8 1% 0+ 129.0 | 136 .4+15.0 
Flowing from brain ae tiie 1253/3 198.8 's.73106 
Flowing from liver otzes | seine | esti 
Flowing from kidneys mats: | tmastaa’ | ieestes 
Flowing from lower limbs | Ss2eet | Whaz%2, | Waegee 
Mixed venous 337°53 783. ryt re : coy ty 

904.2+34.0 | 1366.6+104,3 | 127,8+9,7 

*t poose 


Before ANOH, IgM level was lower and IgA level was higher in blood flowing 
out of the brain than in the systemic circulation (mixed venous and 
arterial blood; P<0.05); IgG level was higher in blood drained from 

the liver than in the systemic circulation (P<0.05). 


After ANOH, we observed a decline of IgA content in blood flowing from the 
brain and lower extremities (P<0.05) and decline of IgG in blood draining 
from the liver and lower extremities (P<0.05). 


There were even more appreciable differences in organic dynamics of the 
parameters, and we observed some new distinctions when we analyzed the 
changes (P<0.05) in their arteriovenous difference. We were impressed 

by the increase in arteriovenous difference for IgA for the brain (from 
~71.6 to +24.2 mg%) and IgG for the liver and lower extremities (-333.3 to 
-20.0 and -200.0 to +73.3 mg%, respectively). Conversely, the arterio- 
venous difference in IgG decreased for the brain (from +76.7 to -195.0 mg%). 
In other words, after ANOH the brain began to “capture” IgA from the 

blood flowing into it and “discharge” into the systemic circulation IgG, 
which in turn began to be “captured” by the liver and lower limbs. 


Thus, this work dealt with organic distribution of the main classes of 
immunoglobulins, IgA, IgG and IgM, each of which is characterized by a 
number of distinctions. For example, IgA play the main role in protec- 
tion of the gastrointestinal tract and tracheobronchial tree, and expressly 
they are the most susceptible to the influence of various deleterious 
factors [2]. IgG, which is present in the highest concentration in blood, 
consists of antibacterial and antiviral antibodies, as well as antitoxins, 
while IgM contains not only specific antibodies, but most natural anti- 
bodies (isoantibodies of the ABO blood group, cold agglutinins, rheumatoid 


113 





factor, heterophil antibodies). We were impressed by the fact that IgM was 
the only class, the organic distribution of which was not affected by 
hypokinesia. 


It is known that the lymph nodes and bone marrow are the main regions in 
which Ig synthesis occurs. For example, IgA is synthesized in the lymphoid 
follicles of the pharyngeal and palatine tonsils, as well as cells iu the 
upper respiratory tract [4]. Im addition, there are indications that the 
lymphoid follicles of the lungs and liver participate in Ig synthenis [5]. 
As shown by the results of our study, the brain and bone and muscle masses 
of the lower extremities play some role in the metabolism of these itactors 
in healthy man; however, it is extremely difficult to assess the physio- 
logical significance of the demonstrated changes without additional studies. 


One of the factors that influences immunological resistance of the organ- 
ism is referable to changes in metabolism. If this is taken into con- 
sideration, the changes in Ig metabolism in the brain become more compre- 
hensible, since substantial metabolic changes were inherent in this organ. 
In particular, we observed compensated metabolic acidosis, increase in 
activity of aspartate aminotransferase and 8-lipoproteins in blood flowing 
out of the brain. These changes were much less marked in the lower 
extremities, or else they were completely absent; at the same time, the 
lower limbs were characterized more by changes in electrolyte metabolism 
and, first of ail, Ca*+, which plays an important role in formation of the 
immunological status [6]. 


In conclusion, it should be noted that our previous studies failed to 
demonstrate substantial changes in Ig of peripheral venous blood at such 
an early stage of bed rest. The results of the present study enable us 
to attribute this to the specifics of organic changes, which were not 
only dissimilar in extent, but in some cases in different directions. Of 
course, these differences were significantly leveled off in mixed venous 
blood, and this determined the relative stability of Ig levels in the 
systemic circulation. 


thus, brief hypokinesia induces in healthy individuals redistribution of 
levels of Ig in blood flowing out of different organs, while their levels 
in the systemic circulation did not change appreciably. Analogous 
studies, including some involving longer simulation of weightlessness, 
must be continued to confirm and provide a fuller explanation of the 
demonstrated changes, which had not been described previously in the 
literature. 


BIBLIOGRAPHY 


l. Mukhina, N. N. in “Aktual'nyye voprosy kosmicheskoy biologii i 
meditsiny"” [Pressing Problems of Space Biology and Medicine], Moscow, 
Vyp 2, 1975, pp 150-152. 


114 














Fischer, C. L., et al. AEROSPACE MED., Vol 43, 1972, pp 856-859. 
Mancini, G., et al. INT. J. IMMUNOCHEM., Vol 2, 1965, pp 235-254. 


Fudenberg, H.; Pink .; and States, D. M. “Introduction to Immuno- 
genetics,” 1975. 


Prokopenko, L. G., and Ravich-Shcherbo, M. I. “Immunoglobulin 
Metabolism," Moscow, 1974. 


Braun, W.; Ishizuka, M.; and Seeman, P. NATURE, Vol 226, 1970, 
pp 945-946. 


115 








UDC: 612.397.7-06:629.78 
RAT PLASMA AND TISSUE LIPIDS AFTER A LONG-TERM SPACE FLIGHT 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 76-78 


[Article by J. Ahlers, R. A. Tigranyan, E. Ahlers, E. Paulikova and 
M. Praslicka, submitted 21 Feb 78] 


[Text] The studies conducted aboard Cosmos-605 and Co mos-690 biosatellites 
revealed that when rats remin in weightlessness for a long time there are 
some changes in lipid metabolism [1, 2]. In view of the distinctions of 
the experiments, the studies were conducted 1 day after the biosatellites 
landed. In the experiment aboard Cosmos-782 biosatellite, the animals 
were examined directly at the landing site. In this way, we could have 
expected that there was no time for the metabolic changes inherent in 
weightlessness to become modified under the influence of returning to 
earth's gravity or during prolonged transportation. 


Our objective here was to study the lipids of plasma and certain tissues 
of rats after completing a flight aboard Cosmos-782. 


Methods 


The studies were conducted on Wistar-SPF male rats 6-10 h and 26 days 
after completion of a 19.5-day experiment aboard Cosmos-782. The obtained 
data were compared to the results of studies on animals involved in a 
synchronous experiment and the vivarium control. We assayed nonesterified 
fatty acids (NEFA) [3] in blood plasma, the liver, white (epididymal) and 
brown fatty tissue (intercapsular); triglycerides (TG) [4] and phospholip- 
ids (PL) [5] in plasma, liver, thymus and bone marrow (humerus); and 

total cholesterol (Ch) in plasma and liver [6]. The obtained data were 
processed by the method of variational statistics with the use of the 
Duncan test [7]. 


Results and Discussion 


After completion of the flight and synchronous experiments, NEFA concentra- 
tion in blood plasma was significantly higher than in intact animals; these 


116 




















changes persisted only in animals in the synchronous experiment after 26 


days. 


After completion of the experiment, plasma TG was also higher in 


aniamls of the flight and synchronous groups than the level observed in 
int ict rats, and this elevation was more marked in the synchronous group; 


virvually no changes were noted after 26 days. 


Plasma Ch did not differ 


from the control in all of the examined animal groups, while plasma Pl was 
appreciably lower in flight animals after the experiment than in the 


control, whereas in the synchronous group they were above the control 
levels after 26 days (Table 1). 


Table 1. Composition of blood plasma and liver lipids 









































| 
Time onditions of 
of ° . NEFA, TG, mgt Ch, mg PL, mot 
study experiment | 9 
Plasma 

6-10 h Intact control 668 +.98 (5) 107,6211,5 (5) 110,2+7,9 (5) 189.626,8 (5) 
after Synchron. exper. 11042 152° (6) | 366,3225,0°° (6) | 127,3213,1 (5) 215,4221,9 (4) 
—-" Flight experim. 13922233° (5) | 231,6228,3°°* (5)| 110,925,615) 155, 526,1"** (5) 
26 days Intact control 4522 103 (4) 186, 7242.8 (3) 95,74 14,1 (5) 159.6% 10,6 (5) 
after Synchr. experin. 13762133°* (5) | 156,94211,1 (5) 106,74 6,4 (S) 198, 526,9 (5) 
experim. ’ . : 

Flight experim. 11824 360 (4) 139,02 10,4 (5) 143.7 = 10,2 (5) 178, St 15,6 (5) 

Liver 

rs h Intact control 3,.7420,48 (6) | 15,7320,65 (6) 4,3320,23 (6) 33,4 20,64 (6) 
after rm | 
experin. Synchr. experim, 3,92 - 0,44 16) 26,0521 ,53°* (6) 4,292.0, 25 (6) 35,421,416) 

Flight experim. 5.9120, 75° (6) | 2,S322,00°° (6) | 4,6920,22 16) 3S 420,96 16) 
26 days Intact control 3,7620,33 (4) 12,3320,88 (6) 4, 2320, 13 (6) 34,024 2,00 (5) 
after Synchr. experim. 4,330.51 (4) | 12,6820,30 16) 4,302.0, 18 (6) 35,82 1,66 (6) 
experim, Flight exverim,. 3,2420,39 (6) | 14,3821,27 (6) 5, 21+0,44 (6) 37, 143,18 (5) 

*P<0.05 **P<0.001 eeRP<O O01 


After the experiment, there was elevation of NEFA and TC in the liver of 
flight animals, as well as of TG ir the synchronous group, as compared to 


the control; Ch and PL content did not change. 


Lipid content of the liver 


was the same 26 days after the experiment in flight and synchronous groups, 
as in control animals (the only exception was an elevated Ch level in 
flight rats; see Table 1). 


In the thymus, an elevation of TG level was observed immediately after the 


experiment only in the synchronous group; we failed to demonstrate changes 
in TG content in the other groups of animals, or changes in PL content of 


all groups examined (Table 2). 


117 














2,45+0 ,49 (5) 
10,54+2,27¢0° (6) 
18,75+ 1 ,62°* (6) 

8,3+1,14 (6) 

5 51 +0, 54 (6) 

15,754 1 ,44°* (5) 


| br 


WEFA/ meq/g 





(6) 


+0,59 (5) 
2,554. 0,17 (6) 


Fatty tissue 


white 
3,294.0 ,57 (6) 

00+40,75°** 
5,954.0 ,46°** (6) 


6, 89+ 1,15 (5) 


10, 
3, 








PL, 
mg/g 

12,94 0,94°** (6) 

12,6+ 1,66 (6) 


20 .0+ 1 ,39 (6) 
24,341 ,09 (6) 
11 ,.4+0,59 (4) 
11 ,9-+0, 46 (6) 





Bone marrow 
,2 (6) 


.9 (6) 
101 ,7+ 16,6 (6) 


117 ,4+17,9 (6) 


_ 
-_ 


’ 


mg/g 
84,7-+12,3 (6) 
103 ,34 14,0 (6) 
87,349 
99,1414 


vi 





(6) 
(6) 


14,840, 26 (5) 
14,54 0,67 


(6) 


14,440,49 (6) 


a 


13,74+0,60 


PL, 
mg/g 
13,840.19 (6) 

13.640,24 





Thymus 


(6) 


63 ,.3+9,3 (6) 


26 days [Intact control] 43,0+8,4 (6) 


(6) 


82,4+10,2 


(6) 
51 .9+12,0 (6) 


TG, 
mg/g 





43,5+8,5 
67 ,7+9,6 





Composition of lipids of the thymus, bone marrow and fatty tissues 


Conditions 
Flight exper. 
Flignt exper. 





Table 2. 
6-10 hiIntact control 


after 
after |Synchr.exper. 


exper. 


exper. |Synchr.exper. 

















TG and PL content of bone marrow of 
rats in 21l groups did not differ from 
control levels [the only exception was 
a significant decline of PL in flight 
animals immediately after the flight 
(see Table 2)]. 


NEFA concentration in white and brown 
fatty tissue was significantly above 
control levels in flight and synchronous 
animal groups, and the changes were more 
marked in the flight rats; after 26 days 
the concentration of NEFA continued to 
remain high in flight animals (see 

Table 2). 


The obtained data indicate that there 
were changec in some parameters of 
lipid metabolism ‘u rats examined 
immediately after completing a flight 
aboard the Cosmos-782 biosatellite. 
There were signs of increased lipolysis 
in fatty tissue and increased mobili- 
zation of lipids. These findings are 
particularly significant because we 
examined satiated animals. It should 
be noted that similar changes, but to 

a lesser extent, were also noted in 
animals in the synchronous ground-based 
experiment. When examined at the re-: 
adaptation stage, i.e., 26 days after 
landing, there was increase in con- 
centration of NEFA in white and brown 
fatty tissue in flight rats only, and 
in blood of the synchronous group of 
animals. As a result of increased 
mobilization of lipids, there was an 
increase in concentration of NEFA and 
TG in the liver of rats in the flight 
and synchronous groups, but it reverted 
to normal at the readaptation stage. 
There were minimal changes in metabo- 
lism of Ch, and they could be assessed 
only by examining Ch synthesis with the 
use of labeled precursors. It should 
be noted that plasma Ch of cosmonauts 
decreased during flights and did not 
change or decreased negligibly after 
them [8]. The main TG levels in bone 


118 




















marrow (humerus) were 3-4 times higher in all groups examined than the 
normal values we obtained for this tissue without significant deviations 
in different groups. The increased lipogenesis could be due to diet (high 
fatty acid, etc., content) or difference in lipid composition of rat bone 
marrow. For this reason, it would be desirable to examine animals that 
are not satiated in the future. 


The changes in spectrum of plasma and tissue lipids under the influence 
of prolonged weightlessness cover a narrow range, and they are an expression 
of insignificant stress, which is well tolerated by the animals. 


BIBLIOGRAPHY 


l. Gayevskaya, M. S.; Ushakov, A. S.; et al. KOSMICHESKAYA BIOL. [Space 
Biology], No 4, 1976, pp 25-29. 


2. Ahlers, J.; Misurova, E.; Praslicka, M.; et al. in “Life Sciences 
and Space Research," Berlin, Vol 14, 1976, pp 185-188. 


3. Dole, V. P., and Meinertz, H. J. BIOL. CHEM., Vol 235, 1976, 
pp 2595-2599. 


4, Eggstein, M., and Kreutz, F. H. KLIN. WSCHR., Vol 44, 1966, pp 262- 
267. 


5. Bartlett, G. R. J. BIOL. CHEM., Vol 234, 1959, pp 466-468. 


6. Zlatkis, A.; Zak, B.; and Boyle, A. J. J. LAB. CLIN. MED., Vol 41, 
1953, pp 486-490. 


7. Duncan, D. B. BIOMETRICS, Vol 11, 1955, pp 1-42. 


8. Balakhovskiy, I. S., and Natochin, Yu. V. "Problemy kosmicheskoy 
biologii™ [Problems of Space Biology], Moscow, Vol 22, 1973, pp 89-194. 


119 














UDC: 612.453-06:613,863).U14.40: 
612.223.1:546.262.31 


FUNCTIONAL CHANGES IN THE ADRENAL CORTEX DURING SIMULATION OF STRESS 
SITUATIONS IN THE PRESENCE OF HIGH CARBON MONOXIDE LEVELS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 78-80 


[Article by S. K. Kalandarov, V. P. Bychkov and V. P. Savina, submitted 
16 Jan 78] 


[Text] When man is confined to an airtight compartment, there is dis- 
charge and accumulation of toxic chemicals. One of the main ones ‘s 
carbon monoxide (CO). 


CO can accumulate in the air of a pressure chamber as a result of its 
constant discharge into the environment in the course of human vital 
functions. The rate of output of CO in exhaled air constitutes, 
according to the data of Sjostrand [1], 0.24 mg/h, which is considerably 
higher than the discharge of other microimpurities. 


CO can also be discharged from polymers. 


Significant elevation of CO level was noted in the case of brief mal- 
function of some elements of the life support system [2]. 


There are extremely few works dealing with the influence of CO on adreno- 
cortical function. As a rule, such studies were conducted in the form of 
brief experiments (up to 6 h/day exposure to CO). Their findings are 
contradictory. Thus, some authors report an increase in adrenocortical 
function under the influence of CO [3, 5, 6], while others, on the 
contrary, report a decrease in activity [7, 8]. 1. M. Peysakhovich [9] 
failed to demonstrate changes in adrenocortical function in animals with 
severe CO poisoning. 


No studies have been made of the functional state of the adrenal cortex of 
man during a prolonged and continuous stay in a pressure chamber with 

high CO content, although it is known that a prolonged stay in an artifi- 
cial atmosphere is a factor with independent biological significance, 
which contributes a number of distinctions to the effect of an altered gas 


120 














environment on the body [10]. Nor have there been studies of the combined 
effect of CO in a high concentration, high temperature and humidity on 

the functional state of the human adrenal cortex during a prolonged stay 
in a pressure chamber. 


We undertook this study for the purpose of preventing occurrence of such 
conditions in cabins of manned spacecraft. 


Methods 


We conducted 4 series of experiments in a 24 n° pressure chamber at 
normal barometric pressure. A total of 16 subjects, ranging in age from 
22 to 36 years (4 in each series) participated in the studies. In the 
lst and 2d series, we examined adrenocortical function with exposure to 
high levels of CO (20 and 15 mg/m°* » respectively). In the 3d series, 

we tested the effect on adrenocortical function of high CO content 

(15 mg/m°* ) and more difficult conditions in the chamber: simulation of 
temporary malfunction of different elements of the life support system 
(LSS). During this time, the temperature in the pressure chamber was 
raised to 32°C and humidity to 87%, withconcurrent increase in CO2 content 
to 3% [2]. 





The lst to 3d series of studies lasted 30 days each. 


In the 4th series, the studies lasted 90 days and CO concentration consti- 
tuted 10 mg/m*. However, in simulating malfunction of the LSS, in addi- 
tion to raising ambient temperature (to 35°C), C02 concentration (to 3%) 
and humidity (to 90%), the CO level was raised to 46 mg/m’. 


For evaluation of glucocorticoid function of the adrenal cortex, we 
assayed ll-oxycorticoids (11-OC) in blood plasma by the fluorimetric 
method of Yu. A. Pankov and I. Ya. Usvatova [11]. 


Mineralocorticoid function of the adrenal cortex was evaluated by the 
levels of sodium and potassium in erythrocytes, since one can make an 
indirect judgment about the level of aldosterone production on the basis 
of concentracion of these elements [12, 13]. Potassium and sodium content 
of erythrocytes was assayed by a unified method using an FPF-58 instrument 
[14]. 


The obtained data were submitted to processing by the method of variation 
statistics, 


Results and Discussion 
We observed an increase (P<0.01) in 11-O0C concentration in blood plasma 


on the 5th day of exposure to CO in a cocnentration of 20 mg/m° (lst series 
of studies). On the 19th day, 11-0C content dropped to the initial level. 


121 














Thereafter (16th, 22d and 28th days), there was an increase in 11-0C 
content of plasma, the maximum rise being observed on the 28th day 
(P<0.01). After the tests, the concentration of plasma 11-OC was below 
the background level (see Table). 


11-OC content (Ug%) in plasma; potassium and sodium content 
(meq/£) in blood erythrocytes of subjects kept in a pressure 
chamber with elevated CO content (M+m) 

















° |____Experimental period, days __Irecove 
Substance | © } Back- | my 
examined 4 |ground; , 10 16 22 28 peri 
~ | period 
-0C 1 | on.041.07/) 36.821.18| 29,943,6 | 32.223.4 | °5.021.9 | 621.9 | 25.021.72 
11 2 Oris | 82,222.) | M227 | 224229 145,120.9 | 29424.02) 27,021,058 
3 26.520.7 | 39.023,3 | 27.7+0.7 | 0.222.4 1023.5 | W.i28.7 | 56.522.0 
K / 83.8 =1.65!) 90.5-2.95) Wael? MG. 7Tei. 19.521,7 100.52".5 90.122.9 
91.222.75) 87.0 24.75) 45.1 = 1,2 | 94,520,863 | 98.1 20.82) B5.025.05) SIL i t8. 
i 92.94 0.67) T8.622.99, "727, 51) . 9) be 3. —_ 91,321.45 
ila 19.3 £0.91 | 17,820.98) 16,420,727) Hewett 114,.9%0.%) 14.0-0.41] 17. 821,22 
2 j 020.9 | 146200 | 15,1207 | 19.9207 [17,2208 | 15.521,7 | 1s.820.4 
3 1 a 16.9 +1.3 13,7205 = 13,120.5 - 15.820.6 























Potassium content of erythrocytes was above the base level (particularly 
on the 19th and 28th days). There was a tendency toward normalization 
of erythrocyte potassium content in the recovery period. The concentra- 
tion of sodium in erythrocytes was below the base levels at all tested 
times. 


In the 2d series of tests (CO concentration 15 mg/m’) the subjects pre- 
sented elevation of blood plasma 11-O0C level on the 4th and 10th days. On 
the 16th day, there was a decrease in 11-OC content. A second, significant 
increase in 11-O0C concentration (P<0.01) was demonstrated on the 22d day 
(see Table). There was little difference from base levels in potassium 

and sodium content of erythrocytes throughout the test period (see Table). 


The results of examining blood plasma 11-OC in the 3d series of studies 
(CO concentration 15 mg /m?*) revealed that the dynamics of changes in blood 
11-OC content were similar to those in the lst series of tests. After 
completion of the study, the concentration of 11-OC remained high (P<0.05) 
(see Table). Potassium content of erythrocytes was low on the 4th 
(P<0.01) and 10th (P<0.01) days of the test (see Table). A slight ele- 
vation of sodium level in erythrocytes was noted on the 4th day and in 

the recovery period (see Table). 


The data obtained in the course of the 4th series of tests revealed that, 
against the background of simulated temporary malfunction of the LSS, on 
the 2lst day of the test the subjects presented an increase in blood 

plasma 11-OC level (37.142.45 yg%, versus 31.5+0.59 wig% in the background 
period). There was another slight increase in plasma 11-0C (35.4+1.21 gz) 
prior to the end of the study (on the 90th day). 


122 











In those cases where normal microclimate conditions were maintained in the 
pressure chamber with CO level of 10 mg/m’, 11-OC content of plasma 
fluctuated over the background range on the 64th and 8lst days of the 
test (29.1+3.66 and 30.824.7 gi, respectively). On the 7lst day, plasma 
11-OC content was somewhat decreased (to 24.622.9 gz). 


The results of our studies indicate that a concentration of 10 mg/m? co 
(4th series) did not affect blood plasma 11-OC content in our subjects, 
whereas in a concentration of 15 and 20 ng/m* this parameter increased at 
certain times, which could be interpreted as increased activity of 
adaptation mechanisms under such conditions. The activity of adaptation 
processes also increased with combined exposure to CO, C02, elevated 
temperature and increased humidity. This was associated with increase in 
glucocorticoid function of the adrenal cortex, whereas mineralocorticoid 
function showed virtually no change. It is known [2] that an increased 
CO level in inhaled air leads to an increase in blood carboxyhemoglobin 
content. This, in turn, induces tissular hypoxia [3, 4]. It was shown 
(6) that adrenocortical hormones, particularly glucocorticoids, enhance 
nonspecific resistance of the body in the presence of hypoxia and, con- 
sequently, they are involved in the process of adaptation to unusual 
living conditions in a pressure chamber with high CO content. 


Thus, the results of our studies revealed that the body adapted to the 
environment of a pressure chamber with the active participation of the 
adrenal cortex. The degree and direction of changes were related to 
the concentration of CO in the pressure chamber. 
BIBLIOGRAPHY 
l. Sjostrand, T. ANN. N.Y. ACAD. SCI., Vol 174, 1970, pl. 


2. Savina, V. P.; Sokolov, N. L.; and Nikitin, Ye. I. KOSMICHESKAYA 
BIOL. [Space Biology], No 6, 1976, p 62. 


3. Vasil'yev, G. A.: Medvedev, Yu. A.; and Khmel'nitskiy, 0. K. 
"The Endocrine System in the Presence of Hypoxia,” Leningrad, 1974. 


4. Tiunov, L. A., and Kustov, V. V. "Toxicology of Carbon Monoxide," 
Leningrad, 1969. 


5. Shtabskiy, B. M. VRACH. DELO [Medical Record], No 7, 1961, p 101. 

6. Pukhov, V. A. "Pathogenesis, Complex Prevention and Treatment of 
Hypoxia,” author abstract of candidatorial dissertation, Leningrad, 
1964. 

7. Berka, I.; Kadlec, *.; Novotny, S.; et al. PRACOV. LEK., Vol 8, 
1956, p 4. 


123 














lj. 


12. 


Fimiani, R., and Castellino, N. FOLIA MED. (Naples), Vol 41, 1958, 
p 454. 


Peysakhovich, I. M. in “Industrial Toxic Agents," Khar'kov, 1928, 
p 147. 


Agadzhanyan, N. A., and Sergiyenko, A. V. DOKL. AN SSSR, SER. BIOL. 
[Reports of the USSR Academy of Sciences, Biology Series], Vol 191, 
No 2, 1970, p 487. 


Pankov, Yu. A., and Usvatova, I. Ya. in “Metody klinicheskoy 
biokhimii gormonov i mediatorov" [Methods in Clinical Biochemistry 
of Hormones and Mediators] by V. V. Men'shikov, Moscow, 1966, p 29. 


Men'shikov, V. V. Ibid, 2d ed., Moscow, 1969, p 145. 


Frenkel’, I. D. "“Neurohumoral Mechanisms of Regulation in Patients 
Suffering From Rheumatoid Polyarthritis and Peptic Ulcer Treated 
With Physical Factors," author abstract of doctoral dissertation, 
Moscow, 1971. 


Mikhaylova, S. P. in “Unifitsirovannyye metody klinicheskikh 


laboratornykh issledovaniy" [Standardized Methods for Clinical 
Laboratory Tests], Moscow, Vyp 6, 1974, p 77. 


124 











64-31-008 ,61]-07 616-008, 934. 55-074 


EFFECT OF HYPOXIA AND HYPERCAPNIA ON LACTATE AND PYRUVATE LEVELS IN RAT 
BLOOD AND MYOCARDIUM 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 80-82 


[Article by N. I. Mikhalkina, submitted 26 Sep 77] 


[Text] We know from the literature that activation of the process of glyco- 
lysis is observed in the heart in the presence of hypoxia, which develops 

in the presence of diseases of the cardiovascular and respiratory systems 
[1-3], significant muscular loads [4-6], as well as altitude hypoxia 

[7-9]. Such factors as increased production of lactic acid (LA) [2] and 
change in level of pyruvic acid (PA), from which LA is formed as a 

result of oxidoreduction with NAD*H2, are indicative of intensification 

of glycolytic processes. 


There is a significant number of works dealing with the study of activation 
of anaerobic processes in the presence of hypoxia [1, 2, 5, 7]. There is 
information to the effect that the combined action of hypoxia and hyper- 
capnia is more effective than their separate effects [10], and that the 
former enhances body resistance to acute hypoxia and other stress factors 
[ll]. This is related to the fact that carbon dioxide has the capacity 
to lower tissular oxygen requirements, diminish affinity of oxygen for 
hemoglobin and thereby causes oxygen to pass from blood into tissues [11]. 
There are also data indicative of the role of the hypercapnic stimulus 

in the control of pulmonary ventilation and stimulation of chemoreceptors 
[10, 12]. Data have been obtained that indicate an increase in delivery 
of blood to the myocardium and stimulation of compensatory and adaptive 
changes in the coronary circulation as a result of the use of hypoxic 

and hypercapnic loads [13]. 


Our objective here was to study the dynamics of LA and PA during recurrent 
brief exposure of rats to hypoxia and hypercapnia. 


125 








Methods 


Experiments were conducted on rats weighing 160-250 g. To obtain the 
effect of the hypoxic-hypercapnic factor, the animals were kept in an 
unventilated place for about 1.5 h daily (2 rats per 7.6 2% desiccator) 
until they developed overt signs of hypoxia. The oxygen content in the 
closed compartment at the end of the exposure period constituted 6.810.037 
and that of carbon dioxide 8.8+0.03%. Experiments were conducted on 

7 groups of rats, which were sacrificed with chloral hydrate (2 g/kg) 
after 1, 2, 3, 7, 10, 15 and 30 days of exposure to hypoxia and hyper- 
capnia. The eighth group served as a control. We assayed LA in blood 

and tissue of the left and right heart according to Barker and Summerson, 
PA by the Natelson method (inmilligram percent per 100 mg tissue or 

100 uk blood). In analyzing the material, we used the estimated value of 
LA/PA, which is also an indicator of intensity of anaerobic processes in 
the opinion of a number of researchers [3, 6, 9, 14, 15]. 


The data were submitted to statistical processing according to I. A. 
Oyvin [16]. 


Results and Discussion 


The data in Tables 1 and 2 show that already single exposure to the hypoxic- 
hypercapnic factor induced changes in lactate and pyruvate concentrations 

in ail specimens examined. These changes were more significant in the 

blood and tissue of the left heart. For example, in left heart blood, LA 
content increased by 164% (P<0.001) and PA by 418% (P<0.05). LA/PA had 

the highest value in left heart tissue (3102; P<0.02). 


We observed further increase in lactate (to 298% in right heart tissue; 

P<0.001) and pyruvate (by 508% in blood of left heart; P<0.05), with the 
exception of a few specimens, on the 2d, 3d and 7th days. LA/PA levels 

were very high (1233 mgZ% in left heart tissue; P<0.01). 


By the 19th day, there was an increase in concentration of LA and PA, 
and PA reached a maximum (the increase constituted 525% in left heart 
blood; P<0.001). In view of the more marked increase in concentration 
of PA at this time there was a decline of LA/PA. 


By the 15th and 30th days we observed a decline in lactate level, although 
it still remained somewhat above control values. There was a drastic drop 
in pyruvate level, for which reason LA/PA remained very high. 


In analyzing the obtained data, it must be noted that there was accumulation 
of lactate in all of the experiments. At the early stages of exposure to 
hypoxia and hypercapnia, this accumulation of LA proceeded with concurrent 
increase in PA, whereas at the later stages not only did the PA level 

fail to rise, it even dropped. This is consistent with data in the 
literature pertaining to two types of metabolic acidosis [14, 17]. 


126 






































































































































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Single exposure to hypoxia combined with hypercapnia induced the maximum 
changes in LA and PA concentration in the left heart. Further exposure to 
these factors led to even more significant changes in levels of the 
recorded products of glycolysis, particularly lactate in the right heart. 
Evidently, this depended on the part of the heart that was subject to 

the greater functional load at any given period of the experiment. Thus, 
under hypoxic conditions the degree of activation of nucleic acid and 
protein synthesis was much more marked in the right ventricle than the 
left [18]. 


There are some difficulties involved in interpreting the low level of PA, 
which was observed in the experiments by the 15th and 30th days of exposure 
to hypoxia and hypercapnia. According to the literature, this could be 
related either to intensification of anaerobic glycolysis [3, 6, 8], 

as indicated by the high values for LA/PA, or intensification of aerobic 
processes through which pyruvate is involved in other elements of bio- 
chemical processes. Additional studies must be conducted to answer this 
question. 


Thus, there are changes in glycolytic metabolism in the rat heart under 
the influence of hypoxia and hypercapnia. 


BIBLIOGRAPHY 


1, Tatarkin, V. M. “Activity of Lactate Dehydrogenase, Levels of Lactic 
and Pyruvic Acids in Blood in the Presence of Circulatory Insuffi- 
ciency," candidatorial dissertation, Moscow, 1966. 


2. Vollenberger, A., and Krauze, Ye. G. in "Korrelyatsiya 
krovosnabzheniya s metabolizmom i funktsiyey" [Correlation between 
Delivery of Blood, Metabolism and Function], Tbilisi, 1969, pp 271-287. 


3. Bulanova, O. N., and Zaks, I. 0. PAT. FIZIOL. [Pathological Physio- 
logy], No 1, 1973, pp 51-53. 


4. Nemirovich-Danchenko, 0. R. in "Vsesoyuznaya nauch. konf. po 
fiziologii, morfologii, biokhimii i biomekhanike myshechnoy 
deyatel'nosti. 9-ya. Materialy" [Proceedings of 9th All-Union 
Scientific Conference on Physiology, Morphology, Biochemistry and 
Biomechanics of Muscular Activity], Moscow, Vol 4, 1966, pp 64-65. 


5. Razumovskiy, Ye. A. in “Vsesoyuznaya konf. po fiziologii, morfologii,. 
biomekhanike i biokhimii myshechnoy deyatel'nosti. ll-ya. Materialy” 
[Proceedings of 1lth All-Union Conference on Physiology, Morphology, 
Biomechanics and Biochemistry of Muscular Activity], Sverdlovsk, 1970, 
p 344, 


128 

















ll. 


12. 


13. 


14, 


15. 


16. 


17. 


18, 


Brodan, V., and Kun, E. CHEKHOSLOV. MED. OBOZR. [Czech Medical 
Review], Vol 17, No 2, 1971, pp 93-115. 


Nazarenko, A. I. FIZIOL. ZH. [Physiological Journal (Ukrainian) ], 
No 3, 1975, pp 377-380. 


Barbashova, Z. 1. “Acclimatization to Hypoxia and Physiological 
Mechanisms Thereof," Moscow--Leningrad, 1960. 


Dudchenko, A. M. in “Mitokhondrii™ [Mitochondria], Moscow, 1976, 
pp 177-182. 


Breslav, I. S. “Voluntary Control of Breathing in Man," Leningrad, 
1975. 


Marshak, M. Ye. “Physiological Significance of Carbon Dioxide,” 
Moscow, 1969. 


Agadzhanyan, N. A.; Davydov, G. A.; and Spasskiy, Yu. A. FIZIOLOGIYA 
CHELOVEKA [Human Physiology], Vol 3, No 2, 1977, pp 343-354. 


Zver'kova, Ye. Ye. IZV. AN KAZAKHSK. SSR. SER. BIOL. [News of the 
Kazakh Academy of Sciences, Biology Series], No 1, 1977, pp 80-83. 


Perevoshchikova, Ye. P. PEDIATRIYA [Pediatrics], No 7, 1972, pp 69-72. 
Neil, W. A., et al. AM. J. PHYSIOL., Vol 204, 1963, pp 427-433. 
Oyvin, I. A. PAT. FIZIOL., No 4, 1960, pp 76-85. 

Huckabee, W. J. CLIN. INVEST., Vol 37, 1958, p 244. 

Meyerson, F. Z.; Mayzelis, M. Ya.; and Malkin, V. B. in 


"Dostizheniya sovremennoy kardiologii" [Advances in Modern Cardio- 
logy], Moscow, 1970, pp 277-288. 


129 








UDC: 615.847.8.017:615.849.1.015.25 


STUDY OF RADIOPROTECTIVE EFFECT OF HIGH-INTENSITY MAGNETIC FIELDS ON 
MAMMALIAN CELL CULTURES 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 83-84 


[Article by Z. Ye. Vnukova, submitted 16 Jan 78] 


[Text] Plans for magnetic protection [1, 2] against ionizing radiation 
served as the grounds for conducting experiments, the objective of which 
was to study the combined effect of fonizing radiation and stationary 
magnetic fields (SMF) on various biological objects [3-8]. There was 
improvement of hematological parameters and a higher animal survival 

rate with a certain combination of these factors [9-11]. Very few such 
experiments were conducted on unicellular organisms and cell cultures, and 
their findings were far from the same [12, 13]. 


We submit here the results of experiments used to study the 
1000 Oe SMF on the effect of gamma radiation on a mammalian cell culture 
in vitro. 


Methods 


In this study, we used two cell cultures: fibroblasts of mice (cell line 
L) and Chinese hamsters (subline 237). The cells were cultured in medium 
199 (L cells) and Eagle's medium (Chinese hamster cells) with 10% bovine 
serum and antibiotics at a temperature of 36.5°C. The radiation effect 
was evaluated according to rate of restoration of cell division, level 

of chromosomal aberrations in the first postradiation mitosis and cell 
survival. The cultures were exposed to radiation from a 137cs source, 

in doses of 200 and 400 R, at a dose rate of 38 R/min. To determine the 
percentage of chromosomal aberrations, we exposed 2-day cultures to radi- 
ation, without exposure to SMF (control) and with exposure to 1000 Oe 

SMF for 2 days, as well as cells after 6-day culturing in SMF (4 days of 
the first passage and 2 days of the second), then fixed them 8 h after 
irradiation. 


130 








We used the method of Puck [14] to determine cell survival. The cells 
were fixed after 10 days of cultivation, and they were divided into two 


equal parts: one irradiated culture was exposed to the SMF and the other 
was not. 


The radiation technique has been described elsewhere [15]. 
Results and Discussion 


There was no change in rate of restoration of cell division 6 h after ex- 
posure to radiation in a dosage of 400 R and SMF. There was also no 
difference between intact Chinese hamster cells and those exposed to 

SMF with respect to level of chromosomal aberrations (see Table). 


Chromosomal aberrations in Chinese hamster cells (%) (Mtm) 


= ooo or” S- oor SO — 























Intact 
Ex 

posure to / 200 n| oo R | cells 

eye | 5,2 0,48 
4,820,43 

- 12,221,38 | 20.421, 
Sessa | (21 |83213 
SMF-R=SiF || 14/220.85 [21,521.55 
Key: R) radiation GMP) expansion not 
SMF) stationary magnetic field known* 


The survival of L cells exposed to GMP* constituted 40.4+2.02% after 
exposure to radiation in a dose of 200 R and 9.7%1.42% after a dose of 
400 R; the figures were 42.2+4.43 and 12.5%+1.25%, respectively, with 
exposure to SMF. The differences are statistically insignificant. Long- 
term exposure of growing cultures to SMF also failed to alter cell 
survival: the survival rate was 28.3+5.11% after 4-day culturing of L 
cells in SMF and irradiation in a dosage of 400 R, versus 30.7143.8% in 
the control (SMF alone). 


These studies revealed that exposure of mammalian cells in vitro to SMF 
before or after irradiation from a source of gamma radiation did not 
alter either the rate of restoration of cell division or the number 

of chromosomal breaks demonstrated in the first postradiation mitosis. 
Different combinations of 1000 Oe SMF and ionizing radiation did not 
change the survival rate for irradiated cells. 





*Translator’s note: GMP appears more than once in this article; MP 
probably refers to magnetic fields, but meaning of G is not clear. 


131 














Similar results were obtained by other researchers [16]. The increase in 
survival rate of animals exposed to radiation after SMF, which was reported 
by Barnothy [6, 7] and Shein [11], may be related to some systemic func- 
tional changes developing under the influence of SMF. 


10. 


ll. 


12. 


BIBLIOGRAPHY 


Trukhanov, K. A.; Ryabova, T. Ya.; and Morozov, D. Kh. “Active 
Protection of Spacecraft," Moscow, 1970. 


Busby, D. £. SPACE LIFE SCI., Vol 1, 1968, pp 23-63. 


Galaktionova, G. V., and Strzhizhovskiy, A. D. KOSMICHESKAYA BIOL. 
[Space Biology], No 6, 1974, pp 25-28. 


Pozolotin, A. A. in “Voprosy gematologii, radiobiologii i 
biologicheskogo deystviya magnitnykh poley" [Problems of Hematology, 
Radiobiology and Biological Effects of Magnetic Fields], Tomsk, 
1965, pp 332-335. 


Idem, in "Vliyaniye magnitnykh poley na biologicheskiye ob"yekty" 
[Effects of Magnetic Fields on Biological Objects], Moscow, 1971, 
pp 186-187. 


Barnothy, M. F. NATURE, Vol 200, 1963, pp 279-286. 


Idem, in “Biological Effects of Magnetic Fields," New York, Vol 1, 
1964, pp 127-131. 


Barnothy, M. F., and Barnothy, J. M. NATURE, Vol 181, 1958, 
pp 1785-1786. 


Abdullayev, M. D., and Zhdanova, S. M. in "Vliyaniye iskusstvennykh 
magnitnykh poley na zhivyye organizmy. Vsesoyuznyy simpozium,. 
Materialy" [Proceedings of All-Union Symposium on the Effects of 
Artificial Magnetic Fields on Living Organisms], Baku, 1972, pp 7-9. 


Savchenko, N. Ya.; Shein, V. I.; and Grigor'yev, Yu. G. in 
"Magnitnoye pole v meditsine" [Magnetic Fields in Medicine], Frunze, 
1974, pp 116-117. 


Shein, V. I. in “Vliyaniye magnitnykh poley na biologicheskiye 
ob"yekty. Vsesoyuznyy simpozium. 3-y. Materialy" [Proceedings of 3d 
All-Union Symposium on Effects of Magnetic Fields on Biological 
Objects], Kaliningrad, 1975, pp 223-224. 


Vlasov, A. Ye. Ibid, pp /2-73. 











13. 


14. 


15. 


16. 





Sosunov, A. V., and Tripuzov, A. N. “Issledovaniya po geomagnetizmu, 
aeronomii i fizike solntsa™ [Studies of Geomagnetism, Aeronomy and 
Solar Physics}, Vyp 17, 1971, p 137. 


Puck, T. T. in “Biophysical Science,” New York, 1959, pp 433-448. 


Sushkov, F. V., and Neyman, 0. V. in "Vliyaniye iskusstvennykh 
magnitnykh poley na zhivyye organizmy. Vsesoyuznyy simpoziun. 
Materialy,” Baku, 1972, pp 125-127. 


Katola, V. M.; Chertov, A. D.; and Gordiyenko, V. P. in “Vliyaniye 
yestestvennykh i slabykh iskusstvennykh magnitnykh poley na 
biologicheskiye ob"yekty" [Effects of Natural and Weak Artificial 
Magnetic Fields on Biological Objects], Belgorod, 1973, pp 69-71. 


133 














UDC: 612.111.3.014.426 
STUDIES OF THE EFFECTS OF STATIONARY MAGNETIC FIELDS ON RAT ERYTHRON 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 84-87 


[Article by A. D. Pavlov, A. I. Solov'yev, Yu. D. Goncharenko and 
Ye. N. Pashukov, submitted 26 Oct 78] 


[Text] There are few data in the literature concerning functional changes 
in erythron under the influence of stationary magnetic fields (SMF), and 
they are contradictory [1-4]. For this reason, our objective here was to 
study the dynamics of erythropoiesis and erythropoietic activity of serum 
in rats exposed to 1000 Oe SMF. 


Methods 


Experiments were conducted on 187 mongrel male rats weighing 160-220 g and 
122 female (CBAXC57B1)F,; mice weighing 16-22 g. The animals were put in 
the SMF in plexiglas containers; the temperature, humidity and light 

were kept constant. They were exposed at the same time of day. The 
gradient of field intensity did not exceed 4% and pulsation of the 
variable component (100 Hz) did not exceed 0.05%. The working space 
between the poles constituted 120 mm and the area was 240260 mn. 


In the first series of experiments we tested the biological effect of 

1000 Oe SMF with 3-h exposure and in the second, with 24-h exposure. We 
assayed erythrocytes, reticulocytes, hemoglobin and hematocrit immediately 
and 1, 3 and 10 days after exposure. We determined erythropoietic acti- 
vity at the same times. In a separate series of experiments, we studied 
the life span of erythrocytes during exposure to SMF. 


Erythropoietin titer in serum samples, expressed in international units (IU) 
of standard B, was assayed by the percentage of incorporation of °9Fe in 
erythrocytes of polycythemic mice. To induce polycythemia, the mice were 
kept at an “altitude” of 6000 m for 18 h/day, for 21 days. We used a 
standard erythropoietin preparation to plot the dose-effect curve. The 
standard was injected intraperitoneally in doses of 0.1, 0.2, 0.5 and 

1,0 IU in two portions, in a volume of 0.5 mf, on the 3d and 4th posthypoxia 


134 














days. Sterile saline with addition of 0.1% albumin was used as diluent. 

On the 6th day, the animals were given intraperitoneal injections of 

1.0 uCi °*Fe in 0.5 m saline. The mice were sacrificed after 24 h to 
assay hematocrit and radioactivity of blood samples, which was determined 
in 0.2 m& samples with a scintillation well-counter. We counted the 
incorporation of Fe in erythrocytes on the basis of total blood volume, 
which constituted 6% of body weight. The effect as a function of dosage 
was plotted on the basis of four points (Figure 1). In our experiments, 

we used a testing system that is a modification of the method of Cotes [5]. 


% 


lér Figure l, 
Erythropoietic reaction as a function 
of dosage in a semilogarithmic system 

wr / of coordinates. 





X-axis, IU; y-axis, 2% uptake of *9Fe 
sb in erythrocytes of posthypoxic poly- 
cythemic mice; b =9,23, SD = +1.436, 
index of precision SD/b = 0.155 





: A. alk. — 


“905 0. 0? 05 70 





The life span of erythrocytes was determined in 19 female Wistar rats 
with the use of °'Cr. A solution of Na2°'Cr0y was injected intraperi- 
toneally at the rate of 7 uCi/100 g weight. Concurrently, Na2°'Cr0, was 
injected in control rats. We took blood samples twice, in a volume of 
0.1 m£, from the caudal vein after 1, 3, 6 and 9 days. Radioactivity 
was determined on an USD-1 with a scintillation counter. Samples 
taken 24 h after injection of *lcr were considered as 100%. 


Results and Discussion 


There was a 74% increase in reticulocytes immediately after 3-h exposure 
to SMF, whereas hemoglobin, hematocrit and erythrocyte count of 
peripheral blood diminished unreliably (Table 1). Erythrocyte count, 
hemoglobin and hematocrit index remained low 1, 3 and 10 days after this 
exposure. 


At these times, there was a 70 and 100% increase in reticulocytes, as 
compared to base levels (see Table 1). Immediately after 3-day exposure 
to SMF, erythropoietin titer in rat blood serum rose by 48%, constituting 
0.089+0.012 IU (versus 0.060+0.001 IU in the control). Serum erythro- 
poietin titer remained elevated 1, 3 and 10days after exposure to SMF 
(Figure 2). 


There was a decrease in hemoglobin and increease in reticulocytes by 40% 
in rat peripheral blood after 24-h exposure to SMF (Table 2). After 1 day, 


135 











there was a decrease in erythrocyte count and hemoglobin content, while 


reticulocyte count remained unchanged. 


After 3 and 10 days, essentially 


the same changes persisted in hemoglobin content, erythrocyte count and 
hematocrit index as 1 day after exposure to SMF. However, the reticulo- 


cyte count remained 60 and 33% higher, respectively at these times. 


The 


erythropoietin titer in serum rose by 22% immediately after exposure 
(0.073+0.006 I1U)and remained high at other tested times (see Figure 2). 














Figure 2. 
Changes in erythropoietic activity of 











3,0- - 
a0se rat serum at different times after 3- 
and ?4-h exposure to 1000 Oe SMF. 
“sr AN 99,087 X-axis, post-SMF time of examination; 
/ \ ee" 2 y-axis: Z 59Fe uptake in erythrocytes 
2.0+ j Se omg 40077 of posthypoxic polycythemic mice, on 
/ jf ah lJ the left; erythropoietic titer in IU, 
nse f/ l " i i 49.068 on the right 
j/ 1) control (saline with 0.1% albumin) 
. ot 1 0060 2,3) 3-h and 24-h exposure, respectively 
” Tmned: 3 0 
nedi- 
ately Days 
Table 1. Peripheral blood indices of rats after 3-h exposure to 
1000 Oe SMF Rh a - 
— Days after exposure to 
Index immedi- 
data ately 1 3 10 
Erythrocytes, 7,020,13 6.90.13 | 6,630.08} 6.2920,06° 6,14=0,07° 
millions/mm (00,0=1.86 | 98,.0=1.84 | 90=1.08 | 89.6=085 | A77=10 
. 15.50.15 | 14,8270,16%| 14.32%0.15*| 14,27 0,13°| 14.3>0,16° 
Hemogionin, 9% (00.00.97 | “95,6=1.03 | 92,4=0,97 | 924=0.84 | GOST 
46.0=0,6 44.520,3° | 44.020.32°| 44,020.32 | 44,6=0,25° 
Hematocrit 100.0=1,.3 | 96,7=0,05| 95.0=0.7 | 95.6=0,7 | 97,020.54 
' 0 27,0=2,3 48,.0=45* | 46,0—3,1 51,0~=6,0° | 54,0=-5,6° 
Reticulocytes, /o0 | [99,0=8,52 | i74,0=16.31| 170,0=11,79| 190,0=22,85) 200,0= 20,74 












































Not 


e: 


We examined 31 animals. 


Here and in Table 2, absolute values 


are given in numerator (Mtm) and % of base level in the 


denominator. 
(P<0.05). 


136 





The asterisks refer to reliable differences 








The tests with *'Cr revealed that the half-life of erythrothrocytes of 
control rats constituted 7-9 days (Figure 3). Injection of *!cr immedi- 
ately after 3-h exposure to SMF failed to demonstrate any differences in 
reduction of radioactivity of blood samples, as compared to control rats. 
Somewhat faster decline of radioactivity in blood samples, as compared 

to control levels, was observed after 24—h exposure to SMF and administra- 


tion of *'cr immediately after exposure; however, the difference was found 
to be statistically unreliable. 















































Table 2. Peripheral blood indices of rats after 24-h exposure to 
1000 Oe SMF 
Days after exposure to 
Index Base r - a 
immedi- l 3 0 
data ately : 
oo ] 
Erythrocytes, 7,00-0,12 | 6,90==0,09 | 6,66—0,i1°) 6,37=0,%6*| 6,45=0,48° 
millions/mm? (00,0 1,71 | 98,021.27 | 95,0=1.57 | 93,0=0.87 | 93,0=1.15 
, 15.00.16 | 14,.52-0,15°| 14,070,17°| 14,070,17° 14,30, 18° 
Hemoglobin, 9% (00.0= 1.06 | 97.0=1.00 | 93,021.13 | 93,021.13} 95,0=1,.2 
H , 45,02-0,36 | 45,070.56 | 45,070.43 | 44,0705 44,07-0,64 
ematocrit [00.0208 | 100,0=1.24 | i0u0=0.95 | 87.0211 | 97.0214 
. 0 27,021,7 38,07 1,28°| 37,072,6" | 43,023,3° | 35,01,3° 
Reticulocytes, /% i00.0=63 | (40.0=4.71 | 137,029.02 ine (33,024.94 











Note: A total of 32 animals was examined. 


Figure 3. 
Change in erythrocyte half-life 
(according to *Icr uptake) after 3- 
and 24-h exposure of rats to 1000 Oe 
SMF. X-axis, time of examination; 
y-axis, radioactivity of blood 
samples (% of base level) 


é 8 28« 





1) control 
2,3) 3- and 24-h exposure 








o 8 


The decrease in erythrocytes, hemoglobin and hematocrit could be attri- 
butable to at least two mechanisms: increased destruction of erythrocytes 
and decreased production of erythrocytes. The data indicative of slower 
biochemical reactions related to so-called paramagnetic molecules (hemo- 
globin, myoglobin, cyanocobalamin, catalase, cytochrome c and others), 
inhibition of active ion transport through membranes, as well as slower 
mitoses under the influence of SMF [6-10] are in favor of the assumption 
that magnetic fields have an inhibitory effect @ rat erythron. The 
normal half-life of °'Cr-labeled erythrocytes immediately after exposure 


137 











to SMF does not confirm the hypothesis that there is a direct deleterious 
effect of 1000 Oe SMF on circulating erythrocytes. However, these data 
do not rule out the possibility that the “deleterious” effect of SMF on 
erythron cells occurs on the level of nuclear erythroid cells of bone 
marrow. Perhaps, this "damaged" population of erythrocytes, which 

begins to circulate several days after exposure to SMF, is indeed differ- 
ent from normal cells in structural and functional properties and has a 
shorter life span. If the hypothesis that there are two possible mechan- 
isms of action of SMF is valid, the slow return to normal of all hema- 
tological indices, as well as dependence of recovery time on duration of 
exposure to SMF, become understandable. 


The increased erythropoietic production in response to SMF indicates that 
there is a change in metabolism of rats exposed to this factor, and it 
induces an increase in 02 requirement of tissues. Intensification of 
erythropoiesis in bone marrow and passage of reticulocytes into blood 
[11-14] should be the consequences of increased erythropoietin production. 
Indeed, an increase in reticulocyte content of blood was observed 
immediately after rats were removed from the magnetic field, and it 
possibly occurred during exposure to SMF. 


BIBLIOGRAPHY 


l. Dernov, A. 1.3; Senkevich, P. I.; amd Lemesh, G. A. VOYEN.-MED. ZH. 
[Military Medical Journal], No 3, 1968, pp 43-48. 


2. Nakhil'nitskaya, Z. N. KOSMICHESKAYA BIOL. [Space Biology], No 6, 
1974, pp 3-15. 


3. Piruzyan, L. A.; Glezer, V. M.; Lomonosov, V. A.; et al. IZV. AN 
SSSR. SER. BIOL. [News of the USSR Academy of Sciences, Biology 
Series], No 1, 1972, pp 142-145. 


4. Barnothy, J. M.; Barnothy, M. F.; and Boszormenyi-Nagy, I. NATURE, 
Vol 177, 1956, pp 577-578. 


5. Cotes, P. M. in "Kidney Hormones,” J. W. Fisher Ed., New York, 1971, 
pp 243-261. 


6. Beischer, D. E. in “International Astronautical Congress, 12th, 
Proceedings,” R. M. L. Baker and M. W. Makemson Ed., New York, 
Vol 2, 1963, pp 515-525. 





7. Gross, L. in “Biological Effects of Magnetic Fields," M. F. 
Barnothy Ed., New York, 1964, pp 74-79. 


138 











8. 


9. 


10. 


13. 


14, 


Reno, V. R., and Beischer, D. E. in “Aerospace Medical Association, 
Annual Scientific Meeting, 37th, Abstracts," Las Vegas, 1966, 
pp 84-85. 


Strzhizhovskiy, A. D., and Galaktionova, G. V. KOSMICHESKAYA BIOL., 
No 2, 1976, pp 63-67. 


Barnothy, J. M. in “Biological Effects of Magnetic Fields," 
M. Barnothy, Ed., New York, 1964, pp 93-99. 


Fisher, J. W.; Lajtha, L. G.; Butoo, A. S.; et al. BRIT. J. HAEMAT., 
Vol 11, 1965, pp 342-349. 


Gordon, A. S., et al. in “Erythropoiesis,"” L. 0. Jacobson and 
M. D. Doyle Eds., New York, 1962, pp 321-327. 


Stohlman, V. Jr.; Brecher, G.; and Moores, R. R. Ibid, pp 162-172. 


Joffey, J. M.; Smith, W. C.; and Wilson, R. S. SCAND. J. HAEMAT., 
Vol 4, 1967, pp 145-157. 


139 











UDC: 613.693:929 Isakov 


PETR KUZ*MICH ISAKOV (70TH BIRTHDAY) 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 pp 87-88 


[Article by editorial board] 


[Text] Prof Petr Kuz'mich Isakov, doctor of medical sciences, laureate 
of the USSR State Prize is celebrating his 70th birthday and 45th year 
of scientific and public activities. 


P. K. Isakov is well-known in our country and abroad as a major specialist 
and pedagogue-scientist in the field of aviation physiology and medicine. 


Petr Kuz'mich graduated from the Rostov Medical Institute in 1937. He 
became interested and showed a skill for research work while still a 
student, when he prepared and published six scientific papers dealing with 
setting physiological hygienic standards and optimizing labor. 


During the years of the Great Patriotic War, P. K. Isakov participated 
in organizing the medical back-up of long-range flights and combat opera- 
tions. He became a member of the Communist Party in 1941; he defended 
his candidatorial dissertation in 1946 and doctoral dissertation in 1959. 


Petr Kuz'mich is an excellent organizer of scientific research and a 
remarkable educator of scientific cadres. More than 20 candidatorial and 
doctoral dissertations have been defended under his guidance. He has 
performed a large amount of scientific research on various problems of 
aviation psychophysiology and medicine, and he has authored more than 

120 scientific works, inventions, textbooks, including "Velocities, 
Accelerations and G-Forces" and "Theory and Practice of Aviation Medicine” 
(coauthored by D. I. Ivanov et al.). 


P. K. Isakov has made a great contribution to the study of the effects of 
G forces on the human body, development of anti-G devices and airborne 
crew rescue equipment in emergency [accident] situations. 


140 




















The profound and comprehensive scientific training of this scientist 
enabled him to become one of the prominent specialists and organizers 
of Soviet aviation medicine. 


The great demands he makes of himself and subordinates are blended with 
Party principle-mindedness, sensitivity, attentiveness and kindness; 

he generously shares with young people his progressive ideas, encyclo- 
pedic knowledge and extremely rich experience in scientific work. 


P. K. Isakov has frequently participated in the work of international 
congresses, conferences and symposiums. His papers are always pro- 
foundly substantiated scientifically and are a worthy representation 
of Soviet aviation physiology and medicine abroad. 


Petr Kuz'mich devotes much attention and time to public service; he has 
been repeatedly elected to the board of the Moscow Society of Physiolo- 
gists; he has been a member of the Higher Certification Commission, 
chairman of the scientific board of the Committee for Physical Culture 
and Sports under the USSR Council of Ministers. 


141 





He is an ardent propagandist and popularizer of aviation medicine. He 
delivers lectures and papers regularly in the system of the All-Union 
"Znaniye” Society, to flight personnel and aviation physicians. He has 
authored scenarios for six popular science motion pictures: “Effect on 
Pilots of High-Altitude and High-Speed Flying,” "On Behalf of Mankind" 
(teaching of I. P. Pavlov on higher nervous activity), “Four-Legged 
Astronauts,” and others. 


For his services to the Homeland, the orders of the Red Banner of Labor, 
Great Patriotic War, second class, two Orders of the Red Star, and 
medals “For Combat Achievements," "For the Defense of Stalingrad," “For 
the Defense of the Caucasus" and others. 


Scientists, scientific workers, pedagogues, aviation physicians and 
specialists, who are members of the section for aviation and space medi- 
cine of the Moscow Society of Physiologists express their sincere 
congratulations to you, dear Petr Kuz'mich, on this jubilee, and wish 
you good health, happiness, long years and new creative achievements for 
the good of our beloved homeland. 


142 








FOR THE INFORMATION OF CONTRIBUTORS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian 
No 1, 1980 p 88 


[Article] 


[Text] Authors must adhere strictly to the “Rules for Conducting 
Studies With the Use of Experimental Animals” arproved by order of the 
USSR Ministry of Health when conducting experimental research: all 
painful procedures on animals must be performed under anesthesia, 

the animals must be removed from the experiments by recommended methods, 
etc. When submitting scientific experimental works for publication, the 
authors must indicate the species and number of animals used, the 
methods used to anesthetize and sacrifice animals. Works for which 

the above-mentioned data are not supplied, as well as those involving 
painful procedures on animals without the use of anesthesia, will not 

be accepted for publication. 

[4-10,657] 


COPYRIGHT: "“Kosmicheskaya biologiya i aviakosmicheskaya meditsina", 1980 


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