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JPRS 84412 


27 September 1983 


USSR Report 


SPACE BIOLOGY AND AEROSPACE MEDICINE 


Vol. 17, No. 4, July-August 1983 








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JPRS 84412 


27 September 1983 


USSR REPORT 


SPACE Brococy AND Aerospace MEDICINE 
Vol. 17, No. 4, July-August 1983 


Translation of the Russian-language bimonthly journal KOSMICHESKAYA 
BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA published in Moscow by 
Izdatel'stvo "Meditsina”. 


CONTENTS 


Some Distinctions of Medical Support of Aviation and Space Missions ... l 


Principles of Organization of Rational Schedules for Crew Work and 
Rest During a Long-Term Spaceflight “ener eeweeweeewee#eeneenreeneeeneeneenerteeee eeeeeee g 


Optokinetic Nystagmus and Optokinetic Stability of Cosmonauts 
in Preflight and Postflight Periods *eeeeeeeeeeeneeeeeeeeeeeneer eee eree ee 14 


Effect of Hypokinesia in Antiorthostatic Position on 
Pulmonary Circulation and Gas Exchange ...esccccccceseseesecsssessses 20 





Contrast Temperatures in Sauna as a Means of Enhancing 
Man's Orthostatic Stability *eeeeeeeveeeeeeeeeeeeeeeeeeneeneeeneeeeeereeee 25 


Effect of Seven Days Without Gravity Load on Velocity and 
Strength of Human Skeletal Bones eevee eveeeeeeeeewve eevee wvneaeeneeenenenenewereneeeee 29 


Morphometric and Gravimetric Study of Rat Heart 
During Long-Term Hypokinesia *eeeeeeneeeeeeeeeeeeeeeeeeneeeaeeee wer eeereeee 36 


Lymphoid Organs of Monkeys Submitted to Antiorthostatic 
Hypokinesia (Experimental Morphological Study) .cccescccssecsessseces 41 


Effect of Spaceflight Aboard Cosmos-1129 Biosatellite on 
Enzyme Activity in Rat Liver *eneeeaeeeeeeeneeeeeeeeeeeeeeeeeneeweewneeemcemhlUcemhUm hm 48 


Role of Gravity in Early Embryogenesis of the Teleost, Brachidanio Rerio 54 


Effect of Centrifuging on Early Embryogenesis of the Teleost, 
Brachidanio Rerio eeeeeveeeeweeneeneneeeeeeneeneneeeneeeneeneeeeneeneeneeeneeee#ee ef vr © 60 


-a- [III - USSR - 20H S&T} 











Influence of Addition of Nitrogen to Inhaled Oxygen 
on Efficacy of 2-Hour Denitrogenation Before Decompression 
from 760 to 220 mm Hg ee ee ee ee ee ee 


Free and Protein-Bound Plasma Corticosterone in White Rats in the 
Presence of Hypoxia and After Administration of Adrenocorticotropic 


Hormone ee 


Some Biological Effects of High-Voltage Stationary Electric Fields . 


Variation Pulsimetry in Evaluating the Effects of Stationary 
Magnetic Fields on Cardiac Function ..ccccccscccccesccsceccscsecece 


Some Distinctions of Nutritional Status When Consuming 
Canned Meat on Emergency ‘Survival’ Diets ....cccccccccccccccccecs 


Optimization of Development of Housefly Larve for Utilization of 
Organic Waste in Biological Life-Support Systems for Man ......... 


Effect of Working in Shifts on Circadian Pattern of Body Temperature 


Measurement of Stroke 2 id Minute Volumes in Monkeys by 
Means of Thoracic Tetrapolar Rheography ....ceccsccccccvcesessccess 


Adsorptivity of Sulfur-Containing Radioprotective Agents .......s.-. 
Effect of Phenibut on Orthostatic Stability *eneeenenenereeneneeneneneeneneenenetee 
Rat Thyroid Hormones Following Flight Aboard Cosmos-936 Biosatellite 


Effect of Long-Term Spaceflight on Catecholamine Content 
of Isolated Nuclei of Rat Brain *reeeeeeneneeneeneneneneneeneneneneneeneneneneneeeneee 


Chromosome Aberrations in Bone Marrow Cells of 
Rats Submitted to Hyperbaric Oxygenation *enerineeeneteneeneerneeeeseee#e#efee#e#e#fee#eee 


Effect of Long-Term Administration of Obsidan on Rat Resistance to 
Hypoxia and Thrombocyte Aggregation During Adaptation to 
Moderate Altitude (1600 Meters) *enereeeneneneneneeneteeneneeneneneneeneeneeneeere#ee#ee 


Role of Central Nervous System in Changing Organ and Tissue Iodine 
Content During Exposure to Variable Magnetic Field ....cecesseseves 


Vasiliy Vasil'yevich Parin (on 80th Anniversary of Birthday) ....... 


66 


70 


75 


81 


88 


100 


107 


113 


118 


123 


126 


129 


133 


136 


140 


144 





English title 


Russian title 


Ed itor 


Publishing house 


Place of publication 


Date of publication 


Signed to press 


Coptes 


Copyright 


PUBLICATION DATA 


SPACE BIOLOGY AND AEROSPACE MEDICINE, 


Vol 17, No 4, Jul-Aug 83 


KOSMICHESKAYA BIOLOGIYA I 


AVIAKOSMICHESKAYA MEDITSINA 


O. G. Gazenko 


Meditsina 


Moscow 


July-August 1983 


10 June 1983 


1428 


"Kosmicheskaya biologiya i 
aviakosmicheskaya meditsina", 1983 








SURVEYS 
UDC: 613.693 
SOME DISTINCTIONS OF MEDICAL SUPPORT OF AVIATION AND SPACE MISSIONS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESVYAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 30 Aug 82) pp 4-9 


[Article by N. M. Rudnyy and I. D. Pestov!] 


[English abstract from source] Comparison of the specific 
features of the environment and human activities in aviation 
and space flights allows us to distinguish the major relations 
in the system man-vehicle-environment as related to their 
medical support. It is concluded that in the aviation flight 
the man-vehicle interaction plays the i.eading role while in 
the space flight the man-environuent interaction comes to the 
foreground. Having in view these differences, medical and 
professional selection, prediction, medical monitoring and 
medical support of pilots and cosmonauts are discussed. 


[Text] Along with recognition of the fact that there is a similarity 

between aviation and space medical problems [1], it should be borne in mind 
that each have their own specifics, in particular with ~* ard to medical 
support of flights. In general, manned air¢raft and spac: craft (FV [flight 
vehicles]) can be viewed as man-machine systems that function in a unique 
environment [2, 3]. Medical support, which is intenced to increase reliability 
of man, as an important element of the system, is an ‘mportant means of optim- 
izing such systems with respect to flight efficiency asd safety criteria. 
However, the environmental factors, living conditions ano activities of man 

in aircraft and spacecraft differ, and they require di’;«.ent approaches to 
medical support of aviation and space missions (see Tr] 


The data in this table enable us to single out the main correlations, from 
the standpoint of medical support, in the man-FV-environment system, as 
related to the distinctions of aviation and space flights. For example, 

the man-FV correlation is relatively more important for an aviation flight 
[2], whereas the man-environment correlation is more so for a spaceflight [3]. 


From the standpoint of medical and professional screening, the priority of 

the man-FV relationship increases the role and significance of psychophysio- 
logical methods and criteria for assessing menory, attention, ability to 
switch attention, speed and precision of responses, resistance to interference 
and other traits required in an operator (visual and auditory acuity, clarity 














irticulation, dark adaptation, binocular vision, etc.). This does not mean 


hat, when screening flight personnel, one can disregard evalustion o! 
resistance to flight factors, which depends on health status. f course, sucl 
resistance is also important to the pilot profession, but it acquires critical 
significance expressly in connection with operator work. The danger of stress 


factors is expressed by pilot error in a more serious form than simply worsen- 
ing of his well-being. 


fhe priority of the man-environment relationship means that attention must be 
focused on safeguarding health during a long-term spaceflight, which 

(neludes screening of cosmonauts with high individual resistance to flight 
factors. Of course, professional, operator qualities are very important per 
se to a cosmonaut, and they must be taken into consideration in the screening 
process; but a good operator can work efficiently, especially in extreme 
situations, if he is not asthenic. 


Ulrimately, pilot and cosmonaut screening based on the above-formulated 
oriorities amounts to concluding that they are "fit" or “unfit” for the 

work to be done in their chosen profession. Since a statement addressed to 
the future constitutes a prediction, it is expedient to assess the specifics 
»f forecasting in aviation and space medicine. The general rule is that 

the closer the subject's state is to the fitness or unfitness standards 
tested in practice, the more accurate the forecast. As applied to aviation, 
such standards are rather reliable, since they are based on a large number of 
observations and long-term experience. At the same time, considering the 
fact that there are many people involved in flight occupations, one should 
consider development of methods of forecasting professional longevity of 
flight personnel on the basis of comprehensive examination of ris! factors 
fraught with the possibility of long-term sec -lae, as well as fitness 
criteria, as an extremely pressing problem ot .viation medicine that requires 
further elaboration. 


The standards of fitness for spaceflights are characterized by less certainty, 
fue to the limited number of cases and wide diversity of missions with regard 
to duration, living conditions, work done by crews, work load and other 
variable factors. At the same time, we know that there are differences in 
osmonaut endurance of spaceflight conditions, which affect his efficiency, 
and for this reason they should be determined as much as possible in the 
course of medical screening. Let us discuss some of these differences and 
to what extent they are predictable on the basis of preflight medical and 
linitcophysiological examinations. 


bifferences in speed at which adaptation to weightlessness occurs have been 
described repeatedly in the literature [4]. They are quite important in 

the practical respect, since they have a serious effect on crew efficiency 
during short-term (up to 3-5 days) missions. Studies of vestibular resistance 
in the preflight period failed to demonstrate a predisposition to a given 

form of adaptation to weightlessness [4, 5], although it appeared that ex- 
pressly vestibular disorders prevail in a state that is not adapted to weight- 
lessness. The correlation between indicators of antiorthostatic [head-down} 
stability demonstrable in the preflight period and severity of disorders that 








ire inherent in the first stage of a spaceflight [6, 7] was foun 
distinct. This made it really possible to classify the form of 
of adaptation to weightlessness on the basis of results of pref] 
of antiorthostatic stability. 


development 


1 te pe more 
ight testing 














Conditions and distinctions of man's habitat and activities during aviation 
a ———2_space missions LS eT 
Compared parameter, ____Aviation flight 0.) ss Spaceflight 00 
Flight dynamics Controllabic course, altitude Ballistic in altitude, velocity 

speed and attitude of air- and plane of orbit; control- 
craft _ lable attitude of spacecraft 
and change in elements of 
orbit 
Duration 'Up to several hours Up to several months 
Recurrence Frequent Speradic 
Intervals between |Hours, days ‘Months, years 


flights 
Main flight factord#Accelerations, load factors, |Weightlessness, isolation, de- 


affecting man noise, vibration, changes in! synchronosis; "housekeeping," 
| barometric pressure, hypoxia, hygienic, sociopsychological 
hypodynamia, heat and emo- | restrictions, psychological 
tional loads, contrasts in | and emotional loads; exposure 
| light, etc. to dynamic factors in powered 
stages of flight 
Functional tasks Control dynamics of flight ‘Control and maintenance of on- 
for crew and onboard systems on the | board systems, research, 
basis oi analysis of ex- | self-care. Periodically: 
terior [outside of cabin] | manual control of flight 
situation, indirect (instru-| dynamics on the basis of 
' ment) information and | analysis of instrument infor- 


| instructions from director mation and instructions from 
of flight | MCC (mission control center) 
Work place ‘Cockpit furnished with arm- j|Working compartments outfitted 


| chair, controls, information! with consoles, means of 
display and communication | immobilization [retaining, 
systems, etc. | holding}, communications; 


| other habitable modules with 
| scientific equipment, as well 
as open space, surface of 








planets 
Elements of Under uncomplicated condi- ‘Under uncomplicated conditions: 
professional tions: performance of oper- performance of monitoring 
activity ator functions in a changing! [inspection] and analytical, 
situation (piloting, naviga-| adjustment, repair-restoration 
tion, monitoring onboard | and other operator, research 
| systems, communications, | and executing functions over 
etc.) _awide professional range 
‘Under complicated conditions: Under complicated conditions: 
| assessment of situation, | detection of malfunctions, 
forecast, making and imple- emergency situations; fight 
menting nonstandard deci- for survival end rescue 


sions with limited time 
and base data 














mtinued) 








—- = 


ared parameter 


Aviation flight 





Fatigue due to nervous- 

| emotional tension, 

| effects of dynamic flight 

| factors, discomfort due | 
to contrived position 

| and use of protective 

| gear 

‘The following may occur in 

_ the course of piloting: 
illusions of spatial 

_ position, vestibulo- 

_ vegetative disorders, im- 

| paired vision and con- 

| sciousness. Probability 

| of altitude-decompression 

disorders, hypoxia, impair- 

ment of heat state in routine 

flight conditions is elimin-— 

ated by using life-support | 

| system and protective gear 


= 


_— _—-- — - — 2 


Canara lL. > 
DAaACeL LI Pi 


_—- — ae ° - - _— -< _ 


Sensory, motor and autonomic 


disturbances when not adapted 
to weightlessness; develop- 
ment of asthenization, de- 
conditioning, diminished 
resistance to stress factors 
as a resulc of "atrophy due 
to inactivity" in weightless- 
ness (deconditioning, des- 
tructive changes in muscles 
and skeleton, changes in hemo- 
poiesis, metabolism, neuro- 
humoral regulation, etc.). 
Additional asthenization is 
possible under the influence 
of habitat and work conditions. 
During pewered flight: func- 
tional changes due to effects 
of accelerations, vibration, 
emotional stress. [In the 
postflight period: sensory, 
motor and autonomic disorders 
related to readaptation to 
terrestrial conditions 





conditions on the ground 
| in periods between flights. 
_ They should be provided in | 
| part aboard the craft during. 
long-distance flights | 


‘Met by creating appropriate | 


= 


Providing comfortable condi- 


tions aboard the spacecraft 
is a mandatory prerequisite 
for assuring vital functions 
and maintaining the crew's 
work capacity 





‘Rapid development of easily 
_ reversible changes; rapid | 
(in hours, a day) recovery | 


' 


ln 
‘Gradual development of adaptive 


changes; slow (weeks, months) 
recovery of initial state 





ii_.iii¢ me 
Changes in funce- 
tional state of 
rew under the 
‘ffect of face 
tors in routine 
‘uncomplicated } 
flight 
jt create 
mfortable con- 
ditions for 
rest and 
recover 
mics of 
inctional 
iange 
} e of 
diminished 
efficiency of 


man-FV syst om 


Inconsistency between char- | 
acteristics and onboard 
systems of aircraft to 
professional training or 

_ capabilities of man to 

| receive and analyze infor- 

| mation, make forecasts, 

| make and implement deci- 

| sions in a changing situa- 

| tion within the required 

| time with the required 
precision 


Instability of initial charac- 
teristics of system due to 
instability of properties of 
man whose functional state 
does not n constant, 
but changes at different 
Stages of flight under the 
effect of weightlessness, 
habitat and professional 
working conditions 


remai 








lable (end) . eS ee ee ee aaa 
Compared parameter’ ss Aviation flight | Spaceflight 0 


} 








Means of improving |Optimization of ergonomic Preserving health and maintain- 


efficiency of | characteristics of air- | ing the necessary level of 
system | craft, refinement of pro- | work capacity in flight by 
| fessional training of | means of a system of preflight 
| flight personnel; preven- | (screening, special training 


| and conditioning for a con- 
cline of pilot work | crete mission) and inflight 

| capacity by methods of | measures: life-support, 

| expert medical evalua- | medical monitoring, thera- 

| tion of pilots, setting | peutic and preventive measures, 

| standards for flight | psychological support; refine- 

| work load, medical moni- | ment of ergonomic character- 

| toring, regulation of | istics of space FV 


| tion of diseases and de- 


schedules for work, rest, 
| nutrition, physical train- 
ing, therapeutic-preventive 
| and health-improving 
' 








measures | 
— — = eens | _ a 
Factors affecting |Reliability of equipment, lReliability of equipment, sta- 
flight safety | professional training of | bility of initial indicators 
(in order of ' crew, stability of initial | of health and work capacity 
decreasing | indicators of health and | of man in flight, professional 
importance) | work capacity of man in | training of crew 
| flight | 
aE a © 4 = " 





Dirferences were periodically found during flights in condition and well-being 
of cosmonauts due to adherence to or infraction of schedules for work, rest, 
sleep, nutrition, exercise, and they were the consequence of objective and 
subjective factors that are difficult to take into consideration [3, 8]. Yet 
it is obvious that any medical recommendations aimed at safeguarding cosmo- 
nauts’ health and work capacity in flight could be beneficial if they are 
followed at the proper time. Otherwise, the state of cosmonauts gets out of 
control, and this creates a situation that does not correspond to plans and 
cannot be predicted. 


The differences in inflight morbidity among cosmonauts indicate that there 
are limited possibilities of predicting diseases in tie course of medical 
screening [9, 10]. Changes in health status of cosmonauts attributable to 
the effect of weightlessness, habitat conditions and nature of professional 
activities could be manifested by development of asthenia, deconditioning, 
diminished constitutional resistance, which creates acditional conditions for 
onset of diverse diseases [9]. It is known that chronic foci of infection, 
with latent course, have a tendency toward exacerbation under conditions that 
simulate weightlessness [il]. This makes it imperative to detect such foci 
also in the course of medical screening of cosmonauts. Considering the pro- 
bability of development of some disturbances during a spaceflight, which are 
referable to the cardiovascular system (in particular, dystonia, extrasystole, 





tunctional changes in the myocardium [12]), as well as digestive system [13] and 
nervous and mental functions [9], it is desirable to Investiy ie predict 
bllity of such disturbances on the basis of indicators of the initial state 


ifferences in readaptation to terrestrial conditions are often manifested 
ifter termination of spaceflights, and they depend on diverse causes. They may 
be based on individual distinctions of the cosmonauts’ organism, as well as 
presence aboard the craft of specific means, adherence to medical recommenda- 
tions for work, rest, nutrition and exercise schedules. For this reason, the 
correlation between disturbances demonstrable in the postflight period and 
distinctions of the cosmonauts’ initial state could be substantially deformed 
by adverse reactions occurring, for some reason or other in flight and 
aggravating its course [3, 8, 9]. Prediction of severity of postflight dis- 
turbances can be made on the basis of in-depth medical examination of cosmo- 
nauts during the flight. This involves, in particular, functional tests with 
sraded physical exercise and lower body negative pressure [9, 12]. Moreover, 
jome rather justified and quite fruitful efforts are being made to predict the 
intensity of postflight orthostatic disturbances in cosmonauts according to 
heir preflight orthostatic stability [14, 15], and degree of bone atrophy 

nm the basis of initial mineralization of osseous tissue [16]. 


lhus, making an expert medical decision as to the flight fitness of cosmonauts 
involves the difficulties of forming a prognosis as to endurance of spaceflight 
conditions. Nevertheless, there are several valid prerequisites for making 
such forecasts, and they could acquire the significance of objective criteria 
in cosmonaut screening as more data are accumulated and determination is made 
of statistically significant functions, thus improving reliability and 
effectiveness of screening. 


At the same time, maximalism of medical screening, which was warranted at the 
early stages of development of cosmonautics, should give way to rationalism. 


it 1s hardly expedient to use the same criteria for screening crew commanders 
ind scientists, researchers, who often present age-related distinctions, 
ome deviations or other in health status, inadequate physical training and 
t always high endurance of stress factors. The requirements of cosmonaut 


lt status may also vary, depending on flight conditions: type of FV, 
its equipment, duration of flight, nature of flight assignment, intensity of 
work load, duration of sleep-waking periods, etc. Taking the above into 
yisideration, it can be considered warranted to advance some general and 
pecial requirements concerning the health status of cosmonauts. 
The following should probably be included in general requirements: absence olf 
conditions that could be instrumental in contracting a disease in flight; 
sychoemotional stability of cosmonauts, their psychological compatibility 
is part of a crew; good (for a commander) or satisfactory (for researchers) 
endurance of extreme factors. One must take into consideration the possibility 
of improving tolerance of such factors by means of ground-based conditioning 
and as experience is accumulated in participation in actual flights. 


The special health requirements for short-term missions include che 
following: high vestibular, antiorthostatic stability; flexibility, 


adaptability and capacity in cosmonauts of mobilizing themselves for highly 











efficient performance, overcoming discomtort, as well as various deprivations 
and restrictions. 


As applied to long-term tlights, the special requirements with respect to 
health status of cosmonauts are: absence of chronic, latent sites of infection; 
high initial mineralization of the spine and orthostatic stability; set of 
specific personality traits (positive aitect for Long-term mission, confidence, 
calm, self-control, ability to distribute strength "over long distances,” 
endurance of deprivation). 


There are also distinctions in medical support of aircraft and spacecraft 
missions with regard to solving such problems as medical monitoring and 
implementing therapeutic-preventive measures during flights. While in avia- 
tion practice such measures are effected under ground-based conditions with 
participation of medical personnel, who use both traditional and special 
diagnostic and therapeutic methods, in the case of manned spaceflights this 

{s done remotely, by means of a limited set of onboard medical apparatus and 
equipment. Expressly thts specific circumstance prompted engineers and 
scientists to develop ways and means of testing and controlliny the state of 
cosmonauts that would meet the contradictory requirements of portability, 
convenience in use and high efficiency, and would also have broad functional 
capabilictes. In particular, development of the means of rendering medical 
care during spaceflights [10] is based on combining a high degree of effictency 
and absence of undesirabic side-effects. All this was, in essence, not only 
an expression of success in medical support of spaceflights, but the condition 
for progressive development of cosmonautics, 


The prospects for further refinement of wa,s and means of medical support ot 
aircraft and spacecraft missions are related to a significant extent to 
progress in the area of research on the distinctions of pilot and cosmonaut 
habitat and activities, and they are governed by the objectives of greater 
safety and effectiveness of flights. 


BIBL LOGRAPHY 


1. Rudnyy, N. M. and Gyurdzhtiav, ». A., KOSMICHESKAYA BIOL., No 2, 1981, 
pp 79-84. 


2. Rudnyy, N. M. and Ponomarenko, V. A., VOYEN.-MED. ZH., No 10, 1975, 
pp 54-60. 


3. Rudnyy, N. M. and Pestov, I. D., in "Chteniya, posvyashch. razrabotke 
nauchnogo naslediya i razvitiyu idey K. KE. Tsiolkovskogo. 10-ye. Trudy. 
Sektsiya ‘Problemy kosmicheskoy meditsiny i biologii'’ [Tenth Lecture 
Serles Dedicated to Development of Sctentific Legacy and Ideas of K. E. 
Tsio'lkovskiy. Transactions. Section on "Problems of Space Medicine and 
Biology], Moscow, 1977, pp 3-10. 


4, Yakovleva, I. Ya., Kornilova, L. N., Tarasov, I. kK, et al., 
KOSMICHESKAYA BIOL., No 1, 1982, pp 20-25. 











LQ). 


fakovleva, I. Ya., Kornilova, L. N., Syrykh, G. D. et al., KOSMICHESKAYA 
BIOL., No 1, 1981, pp 19-22. 


Znernavkov, A. F., Ibid, No 3, 1979, pp 67-71, 


Yarullin, Kh. Kh., Gornmago, V. A., Vasil'yeva, T. D. ect al., Ibid, No 3, 
1950, pp 48-54, 


Rudnyy, N. M., Gazenko, 0. G., Gozulov, S. A. et al., Ibid, No 5, 1977, 
pp 93-40, 


Rudnyy, N. M., Gozulov, S. A., Pestov, I. D. et al., in "Nauchnyye 
chteniya po aviatsil 1 kosmonavtike, 1978 g." [Scientific Lectures on 
\viation and Cosmonautics, 1978], Moscow, 1980, pp 100-112, 


Neumyvakin, I. P., Krupina, T. N., Polevoy, L. G. et al., KOSMICHFSKAYA 
BIOL., No 3, 1978, pp 27-31. 


Genin, A. M., Sorokin, P. A., Gurvich, G. I. et al., in "Problemy 
kosmicheskoy biologii" [Problems of Space Biology], Moscow, Vol 13, 1969, 
pp 247-253. 


Pestov, I. D. and Geratevol', Z. Dzh., in "Osnovv vosmicheskoy biologii 


? 


i meditsiny"” [Fundamentals of Space Biology and Medicine], Moscow, 


4 


Vol 2, Bk 1, 1975, pp 324-369, 


Smirnov, K. V., Syrykh, G. D. and Legen’kov, V. I., KOSMICHESKAYA BIOL., 
No 2, 1982, pp 19-22. 


Kalinichenko, V. Ve>s Asyamolov, B. F. and Zhernavkov, A. F., Ibid, No 5, 
L976, pp 18-23. 


Kalinichenko, Vv. Ve» Ibid, No J, 1977, PP 31-36. 


ttupakov, G. P., Volozhin, A. I., Polyakov, A. N. et al., MEKHANIKA 
KOMPOZIT. MATERIALOV, No 2, 1982, pp 315-321. 








EXPERIMENTAL AND GENERAL THEORETICAL RESEARCH 


UDC: 629.78:612.766.1-08 


PRINCIPLES OF ORGANIZATION OF RATIONAL SCHEDULES FOR CREW WORK AND REST 
DURING A LONG-TERM SPACEFLIGHT 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 28 May 82) pp 9-12 


[Article by A. N. Litsov and V. I. Bulyko] 


[English abstract from source] The work-rest cycles of Salyut-6 
crews were investigated. Several modifications were detected: 
24-hour static regimens (65-70%) and altered regimens (35-30%) 
wiith longer or shorter work-rest cycles. It is concluded that 
in prolonged space flights two regimens are allowed: principal 
regimens (normal static regimens of work and rest) used through- 
out the flight, and operational regimens (differing from 24-hour 
ones) used no more than once every 7-10 days. 


[Text] The present etage of development of cosmonautics is characterized 
by the constant increase in duration of manned spaceflights (MSF) and, 
consequently, increased requirements as to reliability and efficiency of 
crew performance [1-5]. 


Under such conditions, the question arises of organizing rational [optimum] 
work and rest schedules (WRS) for cosmonauts, which are aimed at maintaining 
professional work capacity and safeguarding health status [6-9]. 


Of course, the optimum schedule for the day during a spaceflight is a WRS 
with the customary alternation of sleep and wakefulness in a 24-h day. How- 
ever, in actual spaceflights, it can always become necessary to use not 

only 24-h days, but other cycles, which is related in particular to 

the possibility of occurrence of irregular and emergency situations. 


For this reason, as it applies to space conditions, one should consider it 
possible to use both stationary WRS with 24-h sleep-waking cycles and 
others that differ from the 24-h ones [10]. 


Experimental checking of different versions of WRS on the ground revealed 
that their suitability depends on the extent of the initial shift in 
phase of the sleep-waking cycle, degree of adaptation to them by man, 
frequency and duration of following them. 





Variants of schedules of daily activity of crews as related to 
durationof sleep-waking cycles (7%) 


Table l, 


2s ee ee en ee te me ee se - oe - _ 





A TT 























EXPEDITION (| bAYS) 
SCHEDULE SECOND THIRD FOURTH rirTy 
(140) (175) (185) (75) 
5 94,8 G44 97,2 
5 4 AWAKE AND 9 4 SLEEP 95 94, 4, 
+ M4 AWAKE AND 6 H SLEEP 5 4,1 19 1.4 
\7 4 AWAKE ANDO 7 WH SLEEP 0 1,1 1.7 14 








—— 




















Table 2. Variants of operational schedules for main expeditions to Salyut-6 
station 
wuz EXPEDITION 
OfeRAT ONAL SrconD THIRD FOURTH FIFTH 
pateanteine (140 Davs)|(175 oavs) |(185 oays) (75 pays) 
| 46,2 40 39,1 27,3 
i 23 33,40 26,1 36,4 
at 15,4 13,3 17,4 18,1 
IV 15,4 13,3 17,4 18,2 

















The total number of operational schedules on each expedition 
was taken as 1002. 


Note: 


The feasibility of using the proposed WRS in an actual spaceflight was 
issessed from data obtained during the main (2d-5th) expeditions to the 
Salyut-6 station. 


Analysis of flight data shows that the cyclograms of crew activities con- 
sisted primarily of WRS with 24-h alternation of sleep-waking cycles. 

At all stages of the flight, there was prevalence of schedules with 15-h 
waking periods and 9-h sleep period (95.4%). Other 24-h schedules were 
encountered relatively seldom. For example, a schedule consisting of 16 h 
of wakefulness and 8 h of sleep occurred in 3.6% of the cases, one with 

17 waking hours and 7-h sleep occurred in 1.0% (Table 1). 


[In addition to 24h static schedules, the cyclograms of crew activity 
showed schedules (in 26-30% of the cases) characterized by 1-9-h shifts 

in sleep and waking cycles. The main distinction of these schedules, which 
we arbitrarily called operational, was that they were followed for short 
periods of time for 2-4 days, with subsequent return to the original sleep- 
waking schedule. 


10 





The operational schedules were subdivided into the following subtypes, in 
accordance with the nature of the initial change in sleep-waking cycles: 
[--with initial shortening of waking period (shift to the left of sleep period); 
[I--with initial extension of waking period (right shift of sleep period); 
[II--with initial shortening of sleep period; 1V--with initial extension of 
sleep period (Table 2). 


Subtype I was characterized by initial snortening of waking period from 1 to 
8 h, and it was used during docking and undocking of cargo transport space- 
craft, during rendezvous with visiting crews, refueling of spacecraft. 


Subtype II was characterized by initial extension of waking period to 16-19 h. 
This schedule had to be used to perform operations that were "coordinated" 
with specific flight orbits (orientation of spacecraft, radiocartography, 
taking motion pictures, etc.). 


With the third subtype of operational schedule, there was insignificant 
reduction in sleep period by no more than 1 h. This variant was used to 
perform such dynamic operations as stabilization, correction of orbit, 
pressurizing and bleeding the main hydraulic lines, geophysical experiments. 


Subtype IV, which was characterized by initial extension of sleep period by 
3-4 h, was used during docking and redocking of Soyuz type spacecraft with 
the Salyut-6 station. 


It is apparent from the foregoing that the nature of initial change in 
sleep-waking cycles depends on specific operations, the performance of which 
is directly “tied in" with specific orbits [passes] of flight, and most often 
the waking period was submitted to initial change (shortened or extended), 
the sleep period being changed less often (Table 2). 


Analysis of operational schedules according to degree of shift in sleep-waking 
cycles revealed that it was distributed as follows during the main expeditions 
to the Salyut-6 station (Table 3). 


Table 3. Frequency (%) of operational schedules with different shifts of 


‘ 


gsleep-waking cycles 


—= ee eee ese ee 


EXPEDITION 


_-—— - — _—- ee om —— SCO 
. 
344 SECOND THIRD FOURTH FIRTH 
(140 oavs) (175 pays) (185 pay | (75 oays) 
op TO 3 ' 70 | 55,5 63,3 | 66.6 
3 7064 17,6 7,4 | 26,7 25 
6TO 9W 12.4 3,8 10 R 4 





Consequently, significant shifts of sleep-wakin, cycles (from 6 to 9 h) were 
rarely encountered during actual flights (8.7%). In essence (/4Z% of the 
cases) the shifts were insignificant--up to 3h. 


1] 











Thus, analysis of flight data shows that there is a wide diversity of sleep- 
waking schedules used by the principal crews of Salyut-6 station. However, 
one can distinguish in this diversity a rather clear pattern, namely, that 
two types of schedules were used, one of which (static 24-h sleep-waking 
schedules) was used over the entire flight, while the other (differing from 
static operational schedules) was used for 2-3 days and was followed by 
return to the principal schedule. 


As we know [6, 11, 12], the greater the shift of the sleep-waking schedule 
used, the less acceptable it is and, conversely, the more stable the work and 
rest schedule in relation to 24 h, the more beneficial to the human body. 

The experience with space expeditions revealed that short-term use, for 2-3 
days, of cycles longer or shorter than 24 h does not lead to visible 

decline of professional work capacity and health status of crews on missions 
lasting up to 185 days. 


The foregoing allows us to understand that, in spite of the relative high 
percentage (30%) of use of operational work and rest schedules, these variants 
of daily schedules, when used for 1-3 days, are tolerated by the human body 
without decline of work capacity. 


To sum up our findings, it can be concluded that use of two types of sleep- 
waking schedules, one of which (basic) is a 24=h schedule and the other 
differs from the latter but is used for a short time, can be utilized in 
the 24-h cyclograms of spacecraft crew activities. 


BIBLIOGRAPHY 


1. Alyakrinskiy, Bb. S., "Fundamentals of Scientific Organization of 
Cosmonauts’ Work and Rest," Moscow, 1975. 


2. Ashoff, Yu., in "Chelovek v kosmose" [Man in Space], Moscow, 1971, 
pp 26-28. 


3. Gurovskiy, N. N., in "Ocherki psikhofiziologii truda kosmonavtov"” 
(Essays on Psychophysiology of Cosmonaut Work], Moscow, 1967, pp 5-13. 


4. Nefedov, Yu. G., in "Aktual'nyye problemy kardiologii, klinicheskoy 
fiziologii i kosmicheskoy meditsiny" [Pressing Problems of Cardiology, 
Clinical Physiology and Space Medicine], Moscow, 1979, pp 45-61. 


5. Khrunov, Ye. V., Khachatur’yants, L. S., Popov, V. A. et al., 
"Chelovek-operator v kosmicheskom polete" [Human Operator in Space- 
flight], Moscow, 1974. 


6. Alyakrinskiy, B. S., KOSMICHESKAYA BIOL., No 1, 1980, pp 3-8. 


/. Gazenko, O. G. and Alyakrinskiy, B. S., VESTN. AN SSSR, No 11, 19/70, 
pp 40-46. 


12 











ll. 


12, 


Litsov, A. N. and Sarayev, I. F., in "Psikhologicheskiye problemy 
kosmicheskikh poletov” [Psychological Problems of Spaceflights], 
Moscow, 1979, pp 101-105. 


"Chelovek v dlitel'nom kosmicheskom polete" [Man in Long-Term 
Spaceflights], Moscow, 1974. 


Stepanova, S. I., "Aktual'nyye problemy kosmicheskoy bioritmologii" 
[Pressing Problems of Space Biorhythmology], Moscow, 1977. 


Litsov, A. N., in "Vsesoyuzaoye fiziologicheskoye o-vo im. I. P. 
Pavlova. S"yezd. 13-y, posvyashch. 150-letiyu so dnya rozhdeniya 

I. M. Sechenova. Referaty dokladov na simpoziumakh” [Abstracts of 
Symposium Papers, 13th Congress of the All-Union Physiological 
Society imeni I. P. Pavlov Dedicated to the 150th Birthday of I. M. 
Sechenov], Leningrad, Vol 1, 1979, p 439. 


Alyakrinskiy, B. S. and Stepanova, S. I., in "Kosmicheskiye polety na 
korablyakh ‘Soyuz’. Biomeditsinskiye issledovaniya" [Spaceflights 
aboard Soyuz Series Craft. Biomedical Studies], Moscow, 1976, 

pp 161-183. 


13 














UDC: 617.761.24-02:612.014.477-064) :629.7% 


OPTOKINETIC NYSTAGMUS AND OPTOKINETIC STABILITY OF COSMONAUTS IN PREFLIGHT 
AND POSTFLIGHT PERIODS 


Moscow KOSMICHESKAYA BIOLOCLYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 33 (manuscript received 10 Nov 82) pp 12-15 


[Article by L. N. Kornilova, Yu. V. Kreydich, I. K. Tarasov and I. Ya. 
Yakovleva] 


(English abstract from source] The influence of space flight 
factors on optomotor reactions and optokinetic resistance of 
17 cosmonauts after prolonged (75 and 185 days) and short- 
term (4, 7, 14 days) flights is discussed. 


[Text] Interrogation of cosmonauts and results of tests revealed that opto- 
kinetic factors have some influence on the process of adaptation to weight- 
lessness. It was established that optokinetic interferences not only impair 
tracking and gaze fixation function [1], 2], but could elicit symptoms of 
motion sickness with long-term exposure [3-6]. 


A comparison of resistance of a healthy subject to development of motion 
sickness with exposure to optokinetic and vestibular stimuli revealed that 
even subjects with vestibular stability can develop optokinetic motion sick- 
ness [6], which impairs professional work capacity [7]. 


Our objectives here were to obtain data about the influence of spaceflight 
factors on resistance to optokinetic stimuli and nature of optokinetic 
nystagmus. 


Methods 


We examined 17 cosmonauts (commanders--CDR, flight engineers--FLE and 
scientist-cosmonauts--SC) who had participated in 4-, 7-, 14-, 75- and 135- 
day flights aboard spacecraft of the Soyuz type and Soyuz-Salyut orbital 


complex. 


All of the cosmonauts were deemed to be in yood health according to the 
results of otorhinolaryngological, ophthalmological, physical and neurolo- 
gical examinations, as well as endurance of expert functionai load tests 
on the program of the clinical and physiological examination. 


14 











Optokinetic stability and nature of optomotor reactions to optokinetic stimuli 
were assessed 7 days before the flight, on the 2d and /th days after short 
missions and on the 2d, 7th and 14th days after long-term missions. 


Optokinetic stimuli were created by moving alternating vertical tlack and 
white bands, 3 cm wide, over a semicylindrical screen, from left to right, 
at the rate of 48-50°/s. The distance between the subje 's eyes and screen 
was 30 cm. Stimulation involved the visual field 110° horizontally and 60° 
vertically. Stimulation lasted 6 min. 


The electrooculographic method was used to record eye movements in a horizontal 
lead, on a fluid ["jet'"?] recorder with a time constant of 5s. Optokinetic 
nystagmus was graded in the classification of G. Bado [8]. We determined 

the speed of the slow phase, frequency and amplitude of optokinetic nystagmus. 
In the visual evaluation of the optonystagmographic curve, we paid attention 

to the form of beats, direction of phases and rhythm. We analyzed 10-s 
intervals of the tracing in the lst, 3d and 6th min of exposure to optokinetic 
stimuli. In accordance with their instructions, the cosmonauts had to look 
Straight at the screen, at an "arbitrary" point and mentally count the 

bands traversing it. 


The motion sickness symptoms under the effect of optokinetic stimulation 
were assessed on the basis of intensity of autonomic reactions. The sub- 
jects also gave information about sensory responses. 


Subjects who endured optokinetic stimuli with O grade aut nomic reactions 
were classified as resistant to such stimuli, whereas with grade I or I-II 
vegetative reactions (pailor, perspiration, intensified salivation) and 
complaints of vertigo they were classified in the group who were sensitive 
to optokinetic stimuli. 


Optokinetic resistance and characteristics of optokinetic nystagmus were com- 
pared to the results of testing vestibular function [9] on the same cosmonauts. 


Results and Discussion 


Before the flight, 13 out of 17 subjects presented distinct optokinetic nys- 
tagmus under the effect of optokinetic stimuli; its characteristics were 

in the range of physiological standards: amplitude constituted 5.9+1.7°, 
frequency 3.2+0.6 Hz, slow phase velocity 18.9+2.8 °/s. Four cosmorauts 
presented low-amplitude nystagmoid movements under the effect of optokinetic 
stimulation (FLE of Soyuz-35, CDR and SC of Soyuz-37 and CDR of Soyuz-36). 


Determination of preflight endurance of optokinetic stimulation enabled us to 
arbit.arily divide the subjects into 2 subgroups: resistant (8 subjects) and 
sensicive (9) to optokinetic stimuli. In the latter, we recorded grade I and 
I-II autonomic reactions in the 6th min of optokinetic stimulation: perspira- 
tion, pallor, intensive salivation (in CDR of Soyuz T-2, Soyuz-35, Soyuz-38, 
Soyuz-39, Soyuz T-3 and Soyuz T-4; in the FLE of Soyuz T-3, Soyuz T-4, in SC 

of Soyuz-38). Four of them (CDR of Soyuz T-2, Soyuz-35, Soyuz-38 and Soyuz-39) 
reported vertigo and "heaviness of the eyes due to flickering of bands" 
during the test with optokinetic stimulation. 








Development of MS [motion sickness] symptoms in cosmonauts under the 


influence of vestibular, optokinetic and spaceflight factors 



























































- — “FESTED PARAMETER & ~~ a 
PREFLIGHT POSTFL IGHT 
° *OTOLITH 
SPACECRAFT cosmo & bd . v CAUNCT ION 
T > rk > INFLIGHT 7 r > 
eaeid j F Wi “Ss 3 ¢ wb e 
- z- SYMPTOMS| 3 ~- z- z ‘kh « 
o 4 = J o J - J - x -O Jn 
-_ - x — —_ — x — — wW r ema 
- 2 0 a r @ 0 8 J a Ur-Ue 
n< r< n «< r «< Oo & <rEaZ 
w F af u r a - wW W=Ww-< 
1) ) 7) om j0¢ g>HUU 
oe R ~ - NONE 0 4 (—) | 0 
SOYUZ T.2 ag } » dp ok " 0 0 ' 0 
SOYUZ-35 CDR 4 - 0 ' 0 
FLE - + +- ‘ 0 ' 
SOYUZ- 36 COR , be be 8 , ‘ , 
FLE db 4 = ‘ 0 ‘ 
SOVUZ-37 COR -~+4 ~ 4 ty) 0 0 ( 
SOvYUZ-38 COR ; , " ; , ) 
sc > ‘ " j ’ 
SOYUZ T-3 coR " : ae 
FLEe l ; ; ; 
sc ++ | +4 NONE 0 ¢ | 6 ; 
sovuz T-4 coR ~+ | + " ‘ ‘ | 0 7 
FLE | - PRESENT ; ; f(y é 
SOYUZ-39 COR ro | , NONE 0 ‘ ' ( 
sc - -+ + | PRESENT f 0 0 
| | 
Key: +) average level 
++) high level of vestibular stability achieved after conditioning 
(sensitive) 


+++) high level (resistant) 
) no changes 
(~) nega.ive reflex 
parameter increase 
+) parameter decrease 


Vestibular stability was assessed as high before the flight in 3 (CDR of 
oyuz-35, Soyuz-39 and Soyuz T-4) of the 9 subjects sensitive to optokinetic 


The Table lists data on endurance of vestibular and optokinetic stimuli, as 
well as spaceflight by the tested cosmonauts. 


Interrogation of the cosmonauts on the lst postfligh: day revealed that 

? of them developed sensory and vegetative discomfort and spatial disortenta- 
tion varying in severity and duration during the: flight: in 2 cosmonauts 

(SC of Soyuz-37 and Soyuz-39) of the 8 who were resistant to optokinetic 
stimulation and 5 (SC of Soyuz-38, Soyuz T-3, SC [sic] of Soyu2z-38, FLE of 
Soyuz T-3 and Soyuz T-4) out of 9 who were sensitive to such stimuli, and all 
of them were sensitive to vestibular factors Three cosmonauts (SC and FLE 
of Soyuz-33 and FLE of Soyuz T-3) related ap»earance or intensification of 
motion sickness symptoms in flight to the effect of optokinetic stimuli 
during observations through the window (flickering of light and shade, clouds, 
visible outlines of station and earth). 


16 














(a) Many cosmonauts believed that the abrupt 


. ~& , a transition from the flickering field of 
pacltvicin (oT ow vv one window to another or to the station- 
AAAS IMNInnnl Ww ary interior of the station was the 

factor provoking development of symptoms 
eed of motion sickness. As a rule, most 
cosmonauts succeeded in suppressing 
Horizontal optokinetic nystagmus adverse reactions by means of "rigid" 
in FLE of Soyuz T-4—Salyut-6 (a) immobilization of the body and head, 
and CDR of Soyuz-39 (b). Left-- fixing the gaze on the stationary 
before flight, right--after flight. instrument panel, changing the type of 
Calibration 20°, time scale 1 s work they were doing or active use of 


auto-training exercises. The adaptation 
period lasted 2-3 days, and it was tolerated better when performing active 
professional work. 


After the flight, the optomotor reactions to optokinetic stimuli differed 
from preflight responses in 10 cosmonauts (CDR of Soyuz T-2, Soyuz-36, 
Soyuz-38, Soyuz T-3, Soyuz T-4, Soyuz-39, FLE of Soyuz-35, Soyuz T-4, SC of 
Soyuz-37 and Soyuz-33). The changes were referable to frequency and ampli- 
tude parameters of optokinetic nystagmus, and they were characterized by 
appearance of dysrhythmia (see Figure). 


The changes ir frequency and amplitude parameters consisted either of changes 

in both in tne same direction (in 5 cosmonauts after flight) or increase in 
amplitude and decrease in frequency (in 2 cosmonauts). In some subjects (SC 

of Soyuz-37 and Soyuz-38), the appearance of the nystagmic curve changed and 
dicrotic rises were recorded, against a background of changes in frequency- 
amplitude parameters, and sometimes without change in them. All of the changes 
noted in optokinetic nystagmus were usually associated with nystagmic dysrhythmia. 
It must be noted that, of the 10 cosmonauts who showed changes in nature of 
postflight optomotor reactions, 8 were in the sensitive group and 2 to the 

group resistant to optokinetic stimuli. 


The postflight changes in optokinetic nystagmus, mainly in comsonauts sensivive 
to optokinetic stimuli, were initially related by the cosmonauts to the fact 
that, because of unpleasant sensations from exposure to optokinetic interfer- 
ence, they did not follow the instructions on fixation and counting the bands 
moving through the “arbitrary” point as thoroughly and accurately as before 

the flight. The results of additional tests, in which the cosmonauts paid 
special attention to counting the bands, showed that dysrhythmia was not 
eliminated. 


Determination of optokinetic stability postflight revealed two types of reac- 
tions: either they remained identical to the background (in 6 subjects), or 
else there was a decline of resistance to optokinetic stimuli (in 10 cases). 
Increased resistance to optokinetic stimuli was observed after the flight in 
only 1 cosmonaut (CDR of Soyuz-35). We were impressed by the absence of 
completely identical changes in endurance of vestibular and optokinetic 
factors after the flight (see Table). 


17 








ymparison of the results of testing optokinetic nystagmus to vestibular 


inction postflight in the same cosmonauts revealed that there were changes 
in vestibular function and spatial perception in 8 out of the 10 cosmonauts 
who presented a change in characteristics of optokinetic nystagmus. These 
changes were characterized by appearance of a negative otolith reflex or its 


depression and change in reactivity of semicircular canals (see Table). 


The fact that the changes in parameters of optokinetic nystagmus and vestibular 
sensitivity were in the same direction enables us to assume that the impair- 
ment of frequency and amplitude parameters of optokinetic Relate 20% could 

nave some relation to the change in vestibular excitability. Appearance of 
nystagmic dysrhythmia and change in form of optokinetic nystagmus could be 

due to central regulatory changes and impairment of interaction between affer- 


os Ysctems. 


Thus, it was established that the optokinetic response is associated with 
distinct changes in impulsation of neurons of vestibular nuclei [10-12]. In- 
volvement of the vestibular system in reactions to an optokinetic stimulus 
probably causes, to a significant extent, onset of the so-called pseudo- 
toriolis effect (optokinetic motion sickness). At the same time, it was 
demonstrated [12, 13] that visual tracking reactions (reaction of fixing 
gaze) are based on vestibular afferentation in man, and already on the level 
of vestibular nuclei there is close interaction between proprioceptive and 
l afterentation. 


The changes we demonstrated in thecosmonauts in vestibular function and 
patial perception postflight were indicative of involvement, not only of 

central vestibular structures and integrative mechanisms of the brain, but 
the peripheral part of the analyzer [9]. For this reason, without ruling 

: the role of central elements in development of changes in optokinetic 

nystagmus, we believe that it is also possible that the receptor elements of 


the vestibular analyzer could be involved in these reactions. The existing 

data {14} suggest that the proprioceptive input is involved also in modula- 

tion of vestibular activity (proprioceptive deprivation is instrumental in 

"disinhibition" of vestibular reactions), and this probably affects function 
the oculomotor system. 


us, the results of our studies of optokinetic nystagmus and optokinetic 
ability of cosmonauts indicate that flight factors affect the nature of 
optomotor reactions. There is relationship between them and initial 
resistance to optokinetic stimuli. The observed changes are functional and 
transient, since they were only demonstrable for several days after landing. 
in view of the noted selective sensitivity to optokinetic stimuli and post- 
flight change in optokinetic nystagmus, it is deemed desirable to assess in- 
jividual endurance of optokinetic factors, as well as to determine the 

‘inctions of optokinetic nystagmus in response to the delivered stimuli, 
nm confunction with the set of tests of vestibular function in cosmonauts. 


r? 


BIBLIOGRAPHY 
1. Balashova, Ye. G., FIZIOL. ZH. SSSR, No 7, 1975, pp 1072-1076. 


18 











; 


LO. 


A 


t “ tr . ’ ‘ 7 : ‘ ‘ ‘ 0 « ’ , ‘ 
Kreydich, Yu. V., Repin, A. A. and Barmin, V. A., in AviarosmicheskKaya 
meditsina’ [Aerospace Medicine], Moscow--Kaluga, Pt 2, 19/79, pp 1/9160. 


Frederickson, J. M., ACTA OTO-LARYNG. (Stockholm), Vol 61, 1966, 
pp 168-188, 


Dichgans, J. and Brandt, Th., Ibid, Vol 76, 1973, pp 339-345. 


Idem, BIBL. OPHTHAL. (Basel), No 82, 1972, pp 327-338. 


Kornilova, L. N., Shakhiyeva, V. A. and Yakovleva, I. Ya., KOSMICHESKAYA 
BIOL., No l, 1982, pp 67-70. 


Kornilova, L. N., Kravchenko, S. L., Smirichevskiy, L. D. et al., Ibid, 
No 4, pp 17-20. 


Bado, G., ARTIF. SATELLITES, Vol 8, 1973, pp 93-97. 


Yakovleva, I. Ya., Kornilova, L. N., Tarasov, I. K. et al., 
KOSMICHESKAYA BIOL., No 1, 1982, pp 20-25. 


Lackner, J. &. and Teixeira, R. A., AVIAT. SPACE ENVIRONM. MED., Vol 48, 
1977, pp 248-253. 


Teixeira, R. A. and Lackner, J. R., Ibid, Vol 50, 1979, pp 264-266. 


Kurashvili, A. Ye. and Babiyak, V. 1., "Physiological Functions of the 
Vestibular System," Leningrad, 1975. 


Repin, A. A., "Investigation of Mechanisms of Cerebellar Control of 


Vestibulo-oculomotor Reactious," candidatorial dissertation, Moscow, 1981. 


Ayzikov, G. S., "Role of Motor Analyzer in Manifestation of 
Labyrinthine Reactions,’ doctoral dissertation, Moscow, 1976. 


19 








UDC: 616.131-02:612.766.2 


EFFECT OF HYPOKINESIA IN ANTIORTHOSTATIC POSITION ON PULMONARY CIRCULATION 
AND GAS EXCHANGE 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 16 Jun 82) pp 16-18 


[Article by V. Ye. Vorob’yev, V. R. Abdrakhmanov, I. V. Kovachevich, A. P. 
Golikov, L. L. Stazhadze, V. V. Bogomolov, S. G. Voronina and L. G. Repenkova] 


[English abstract from source] The purpose of the study was to 
investigate gas exchange and lung p*rfusion during 14-day head- 
down tilt and immediately thereafter. During head-down tilting 
pulmonary circulation increased, as suggested by zonal rheo- 
graphy of the lungs and by ECG (increase in the Py; -y7]; amplitude 
and width by 1-2 mm and 0.01-0.02 s, respectively). A signifi- 
cant decrease in 0, tension and slight increase in CO2 tension 
of the arterial blood were detected. Immediately post-test 
pulmonary circulation declined and metabolic acidosis developed 
simultaneously. Our findings suggest that drugs reducing pul- 
monary hypertension can be recommended for emergency medical aid 
in space flight. 


[Text] As a rule, when man spends a long time under hypokinetic conditions 

in antiorthostatic [head down] position (AOH), there is change in vascular tonus 
in the pulmonary circulatory system, noticeable increase in delivery of 

blood to the upper branches of the lung and reduction of all lung volumes 

[l, 2]. According to the data of A. P. Zil'ber [3], postural factors 

have a marked effect on intraorganic redistribution of pulmonary blood flow. 
This, in turn, cannot fail to affect gas exchange dynamics. However, no 
comparative studies were made of parameters of external respiration and 
regional pulmonary circulation under AOH conditions. 


Our objective here was to conduct a combined study of gas exchange and 
regional pulmonary perfusion in subjects submitted to AOH and in the 


early recovery period. 
Methods 
We studied external respiratory function, gas composition and acid-base 


balance (ABB) of arterial blood under basal metabolic conditions in 9 
essentially healthy subjects during 14-day AOH with -8° angle of inclination 


20 





and in the early recovery period. We used Wright's electronic spirometer 

to meausre minute volume of respiration, a capnograph and paramagnetic oxygen 
analyzer to analyze the gas composition of exhaled air. Samples of arterial 
blood taken by puncturing the radial artery were immediately examined by the 
Astrup method on an AME-1 apparatus. Nonelastic respiratory resistance was 
det.cmined by the oscillation method using a "Siregnost FD-5" unit. 


Concurrently, we recorded rheograms of the superior, central and inferior 
segments of the right lung using a 4RG-lLA rheograph and encephalograph of 
the Galileo Firm. The obtained data were analyzed by conventional meth ds 
[1]. We calculated the rheographic index (RI), which reflects the intensity 
of filling of the tested region with blood, dicrotic (DCI) and diastolic 
(DSI) indexes, which characterize arteriolar and venous tonus, respectively, 
as well as the a/T ratio, which indicates the tonus of large and medium 
caliber vessels. 


The EKG was recorded from 12 leads on a Mingograph-82. All of the tests 
before AOH and in the recovery period were conducted with the subjects in 
horizontal position, during hypokinesia they were tested in head down 

, osition. 


Results and Discussion 


During AOH, the EKG showed increase in amplitude of Prrerry wave Ly 1-2 mm 
and widening by 0.01-0.02 s, as well as depression to i mm of Sy5-y6 wave 
in some subjects. 


Already on the 2d-3d day of hypokinesia, lung rheograms showed a reliable 
increase of a/T ratio in the superior (from 16.89+41.61% in the background 
period to 21.68+2.55%; P = 0.05) and central segments of the lungs (from 
21.05+2.56% in the background to 26.54+1.14%; P<0.05), as well as consider- 
able rise of DCI in the upper segments of the lungs (from 31.25+7.95% in 
the background to 60,98+15.07Z; P<0.05), which was indicative of increased 
tonus of arterial vessels in the upper and middle segments of the lungs. 
These changes did not progress subsequently. At the same time, throughout 
the AOH period, we observed a distinct tendency toward decreased delivery of 
blood to the lower segments of the lungs, which was particularly marked 

on the 10th day of hypokinesia (RI 1.67+0.29 in the background period, 
1.0+0.13 on the 10th day; P<0.05). 


The findings are an indirect indication of the fact that, during AOH, 
there was an increase in overload on the pulmonary circulation. 


Against this background, we demonstrated a drop of 0» tension, as compared 

to background levels, which was reliable on the 10th day of hypokinesia 
(P<0.05) and a tendency toward retention of CO, (Table 1). The alveolar- 
arterial gradient for oxygen rose by a group average of 8.3 mm Hg, whereas 
the arterifal-alveolar gradient for carbon dioxide rose by only 0.7 mm Hg. No 
appreciable changes were demonstrated in blood ABB. In addition, we ob- 
served a gradual increase in nonelastic respiratory resistance from 3.53t 
0.21 mbar/2/s in the background to 4.69+0.24 mbar/?2/s on the 10th day of 


21 











AOW (P60,.05). Lt should be noted that slight hyperventilation was found in 
the subjects at the early stage of hypokinesia. On the 13th day of AOH, 
the severity of changes in the parameters tested diminished, 


fable 1. Dynamics of parameters of external respiration, gas composition 
and ABB of arterial blood during AOH and in the recovery period 


oe - ™ _- 


oe: 7 | ee | 











Period | oH St | Lt P APA ~a0, | APa~—Atl 
. 
Background (before AOH) | (426 | 24 02 | 994 17.4 () 
1) O04 | : 0,25 © 0,27 » | $/ | 76 ‘- 14) 
} iY of AOH | 7,410 | 24 ) | ).4 Ky 7° ‘ Z io ] 2 
d +O 0O}) ~O 26 0,40 9 95 | 1 40 o 4] 1.09 
| | 
4 7,429 23,9 05 90 0 7 | & i? 
‘7 iaYy yf sOH ' ' 
’ 0,008 | +0,56 ~0.42 | +£2.96 | 151 2 QR | 69 
t day of recovery 7,396 22,7 2,1 R6,) 8 | 181 1,9 
oY ) 4 , f) O04 . 0.60 , 0.75 4 G4 | j | GY ’ / 1 
, ” "yt fad . ‘ 
j4 day of recovery / 404 22,4 24 93,7 | 6.5 | 5.5 04 
Y | +0,008 “0,41 | + 0,48 |i 149 | +08 1,f 
i’ | | 





Note: Here and in Table 2, the asterisk shows statistically 
reliable differences (P<0.05). 


4) active reaction of blood 
SB) standard bicarbonates (in mmol/27) 
BE) base deficit [sic, should be base excess] (mmol/?) 


» and CO» tension in arterial blood (mm He) 


20>) alveolar-arterial gradient for 0, (mm Hg) 
‘Pa-ACO,) arterital-alveolar gradient for CO, (mm Hg) 


, 


ic can be concluded that under AOH conditions, elevation of pressure in 
nonary circulation is associated with heterogeneous distribution of 
ary blood flow, manifested by a significant decrease in filling of 
rior lmonary regions. 


the same time, elevation of pressure in the pulmonary artery could stimu- 
{lation in a reflex fashion [4]. This probably explains the 


ri - in respiratory minute volume on the first days of hypokinesia. 
ntly, the combination of hypertension in the pulmonary circulation and 
niform pulmonary perfusion is one of the chief causes of the demonstrated 
in gas composition of subjects’ blood. At the same time, we cannot 
nut a decrease in alveolocapillary diffusion of gases, particularly in 


ses of hemostasis in the lungs. However, in view of the high diffusion 
ity of CO,, we think it more correct to consider this a secondary 
inism in the genesis of deviations of gas exchange under the effect of 


long-term AOH. 
the | of the lst day of the recovery periou, we demonstrated a signifi- 
int decrease in intensity of filling in all regions of the lungs, as compared 


22 








to the background, and this was more marked in the basal regions of the Lungs 
and was associated with increase in vascular tonus (Table 2). On subsequent 
days these changes gradually leveled off. 


Table 2. Dynamics of parameters of regional pulmonary circulation in the 
recovery period 


Lung | Recovery period — 








| Be fore |—__—_— i 
ter | ' 

zone | Paramete » | AOH 2d day | Sth day 
, | e 

Superior RI | 1874024 | 1 2440.16" 1 Hk + 0,25 
| DCI ’ % | .} 254 7 O5 We i? QQ $f, “J 1") 70 
DSI, % i) iJ 9S Varir ow s] ml el 

a/T, . | 16,89 1 6) 19, BR 2.56 IR Ale 14 

RI 1 64 +0,27 | 1.0940.097" | 1,520,135 
Middle DCI, © | 28,9545.25 | 59,4647.46 | 56,39 11,35 
DSI, % 15,60» 2.73 55,.96+7,19 | 63,07+12.35 

a/T, % 2168+ 2,56 24,65+2,35 | 17,QR—2.58 

RI | | ,67+0,29 0864014 | 1084015 

Inferior DCI, *% 41 ,64+45.81 62,084 7,49 | «83,1 + § 80 
DSI, © | 44,99-+6.33 K9.16+19.07° | 64,03— 10,21 

a/T, % | 27,224 3,02 25,084. 5,26 | 23,74=2.63 





- -- _——_— + -_-—]— -- - -_—- ———_ - a ee ae - -_—-— 


Immediately after AOH, we observed a tendency toward decline of 0, and CO, 
tension, as compared to the background, with concurrent presence of acidotic 
changes in ABB of blood, mainly metabolic in nature. With retention of a 
tendency toward increase in gradient for 0,, the gradient for CO, was within 
the physiological range. 


We can assume that the diminished filling of all pulmonary zones and uneven 
regional blood flow, which are probably due to change in regulation of 
circulation in the human body under the effect of AOH [5, 6], may be a possible 
cause of gas exchange shifts in the subjects in the early recovery period. 


These results, as well as the results of prior studies [7, 8], must be taken 
into consideration when elaborating methods of rendering medical aid at 
different stages of manned spaceflights. Thus, in the event of development 
of acute life-endangering states during a spaceflight, there is a high 
possibility of rapid onset of a serious complication, such as pulmonary 
edema, This requires inclusion in the conventional systems of rendering 
first [emergency] aid agents that diminish intrapulmonary hypertension, in 
particular, osmodiuretics. The relative hypovolemia of the lower parts of 
the lungs increases the danger of atelectases of these regions in the presence 
of any forms of hypoxia and hypoxemia. We believe that there is theoretical 
validity to the recommendation to use periodic inhaling of 0» through a mask, 
at excess pressure of up to 15-30 mm Hg in the presence of pulmonary compli- 
cations, and this is consistent with the data of V. G. Voloshin et al. [9]. 
The most effective method is artificial ventilation of the lungs in a mode 
of moderate hyperventilation at positive pressure, against a background of 
tctal relaxation and dehydration therapy, but it cannot be used without 

a specialist physician. 


23 





Data pertaining to development of irregular pulmonary perfusion and decreased 
filling of pulmonary tissue in the early recovery period must be taken into 
onsideration when elaborating the set of rehabilitation measures, in parti- 
eular, to regulate motor activity and methods of breathing exercises. 


BIBLIOGRAPHY 


l. Yarullin, Kh. Kh., Krupina, T. N., Vasil'yeva, T. D. et al., 
KOSMILCHESKAYA BIOL., No 4, 1972, pp 33-39. 


Katkovskiy, B. S. and Andretsov, V. A., Ibid, pp 55-59. 

Zil'ber, A. P., "Clinical Physiology for Anesthesiologists," Moscow, 1977. 
4. Ledsome, J. R., AM. REV. RESP. DIS., Vol 115, 1977, pp 245-250. 

5. Kakurin, L. I., in "Aktual'nyye problemy kardiologii, klinicheskoy 
fiziologii 1 kosmicheskoy meditsiny" [Pressing Problems of Cardiology, 
Clinical Physiology and Space Medicine], Moscow, 1959, pp 52-54. 


6. Krupina, T. N., Ibid, pp 55-59. 


Golikov, A. P., Vorob’yev, V. Ye., Abdrakhmanov, V. R. et al., 
KOSMICHESKAYA BIOL., No 1, 1980, pp 42-46. 


4, Stazhadze, L. L., Bogomolov, V. V., Goncharov, I. B. et al., ANEST. I 
KEANIMATOL., No 5, 1980, pp 14-18. 


9. Voloshin, V. G., Karpusheva, V. A., Asyamolov, B. S. et al., 
KOSMICHESKAYA BIOL., No 1, 1982, pp 38-40. 





24 





UDC: 615.832.1.015.4:612.763-08 


CONTRAST TEMPERATURES IN SAUNA AS A MEANS OF ENHANCING MAN'S ORTHOSTATIC 
STABILITY 


Moscow KOSMICHESKAYA BIOLOCIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 10 Mar 82) pp 19-21 


[Article by V. I. Subolevskiy] 


[English abstract from source] Contrast thermal effects in 
the sauna bath help increase orthostatic tolerance. This is 
associated with a lower increase of heart rate, an increase in 
pulse pressure and a smaller change in ECG and PCG in the 
standing position. It is recommended to use contrast thermal 
effects of the sauna bath to maintain and improve man's 
orthostatic tolerance. 


[Text] Investigation and evaluation of the practical value of new methods 
of maintaining and enhancing man's orthostatic stability constitute a 
pressing problem of aerospace medicine. Previously, studies were made of 
the combined effect of thermal procedures in a Massarskiy chamber and cold 
rubs on orthostatic stability [1]. In this work, changes were observed in 
parameters of the active orthostatic test under the influence of total- 
body contrast temperatures in a sauna, which is used extensively as a 
hygienic, rehabilitation and conditioning factor for the circulatory system 
[2]. 


“etheds 


A total of 30 (lst group) and 20 (control, 2d group) essentially healthy males 
20-39 years of age participated in these studies. Ambient temperature in the 
sauna was 90°C, relative humidity 5-15%, duration of exposure 2~10 min, with 
a 5S-min rest period. After each exposure in the hot sauna room, the sub- 
jects took a shower for 40-60 s (at temperature of 12-17°C). Before heat 
exposure in the sauna, 30 and 90 min after it, we conducted the active ortho- 
static test [3], recording the electrocardiogram (EKG) and arterial pressure 
(BP) in the lst, 3d, 5th, 7th and 10th min in erect position. In addition, 
polycardiography (PCG) was used in the lst and 10th min in orthostatic posi- 
tion to assess the phase structure of the cardiac cycle according to V. L. 
Karpman. We measured fluid loss before and after the sauna bath by weighing 
the subjects and taking their sublingual temperature. 


25 











Results and Discussion 


Before the sauna, there were no reliable differences between the first and 
second groups, with respect to pulse rate, BP, EKG and PCG, in both the 
background period and during the orthostatic test. Sublingual temperature 
rose to 38.1%.06°C (P<0.001) and pulse rose to 109+6.8/min under the 
influence of exposure to contrasting temperatures in the sauna. In supine 
position, the above parameters constituted 37.0+0.07°C and 78.3+3.1/min, 
respectively, after 30 min, 37.040.1°C and 74.744.8/min after 90 min in the 
first group. The Table lists the findings as to effect of exposure to 
contrasting temperatures on pulse increment in the orthostatic test. As 
we see from the submitted data, there was reliable decline of pulse rate 
increment after the sauna, particularly after 90 min, as compared to both 
parameters of the first group and in the course of ongoing readings in the 
first group (see Figure). We found 
less marked changes in the EKG of the 
first group 90 min after the sauna, 
4 A in the 10th min of orthostatic position, 
; than in the control: 26.7% less decline 
of T wave (P<0.05), 0.03+0.008 s less 
shortening of Q-T interval (P<0.05). 
At the same time, the PCG data were 
indicative of shortening of ejection 
period by 0.048+0.008 s in the control 
——— a — and only 0.016-).007 s in the first 
group (P<0.05). It is known that 
shortening of ejection period in the 
orthostatic test occurs because of 
diminished venous return of blood to 
the heart and decrease in stroke 
volume. Less filling of the ventricles 
Se has an adverse effect on the force of 
cardiac contraction: isometric contrac- 
| tion time is extended (by 0.010+0.007 s 
(3 in the 10th min of erect position 90 
min after the sauna, versus 0.012+0.005s 
in the control) and the instrasystolic 
indicator diminishes (by 1.9+0.3 and 
5.8+1.8%, respectively). Since these 
b C d PCG parameters changed less in the 
first group than in the second, it can 
janges in heart rate (per min, A), be assumed that there was also less 














pulse pressure (um Hg, B) and change in venous return to the heart 
ejection period (in seconds, C) on in orthostatic position after the sauna. 
PCG during orthostatic test before It is significant that there were no 
and after sauna (first group) reliable differences between background 
X-axis: findings for the first and second groups 


1) before sauna 

2) 30 min after 
sauna 

3) 90 min after 


i) l min 

b) 10 min (supine) 
c) 1 min 

Jd) 10 min (standing) 


30 and 90 min after the sauna, before 
the orthostatic test. 


The BP changes were also indicative 
of the beneficial effect of sauna 


26 











on the nature of changes in orthostatic test indicators. This was shown by 
the relatively less marked lability of systolic and diastolic BP, as compared 
to the control, and progressive increase in pulse BP: 90 min after the sauna, 
in the 10th min of the orthostatic test, the pulse BP increment constituted 
2.83+0.3 mm Hg in the first group, whereas in the second group of subjects 
pulse BP dropped by 7.2+0.41 mm Hg (P<0.05). 


Dynamics of heart rate during orthostatic test under the 
effect of exposure to contrasting temperatures in sauna (Mtm) 





LL OLE A A et tt et Nl 





After Sauna 

















Time of after 30 min after 90 min 
Parameter reading ar 
| first | second | first | second 
! | a 
lst min of | 16.794 1.069 9 . 2 
_ | ' 1,7 2+1,96 23,81+2,1 12,03+ 1,86 24,12+3,16 
Heart rate | orthostasis 
t.... \ J. Ss | 
per min y . 
10th min of 17,8141,32 | 20,9441,87] 10,7141,47* | 18,79+2,37 
orthostasis 

















*Reliability of differences as compared to control (P<0.05). 


Since the results of previous studies [2] indicated that the physiological 
effect of exposure to heat in a sauna is largely determined by the extent 

of dehydration, it should be noted that weight loss was insignificant in the 
first group of subjects (0.5710.04% of initial body weight) and comparable to 
the results of the studies of V. V. Zhidkov et al. [1], who cited 0.410.037 
dehydration. 


It is known that during exposure to heat in a sauna, provided excessive fluid 
loss is restricted, there is improvement of coronary circulation and oxygena- 
tion of the myocardium [4], as well as increase in circulating blood mass, 
intensification of reflex and neurohumoral regulation of vascular tonus, 
including venous tonus [5]. These factors, in turn, are the deciding ones 

in the body's response to active orthostasis [6]. 


Thus, the chanzes in parameters of the active orthostatic test under the 
influence of exposure to contrasting temperatures in a sauna are indicative 
of improvement of man's orthostatic stability. These findings are indicative 
of the desirability of making practical use of contrast temperatures in a 


4 


Sauna to maintain and improve man's orthostatic stability. 


BIBLIOGRAPHY 


1. Zhidkov, V. V., Borshchenko, V. V. and Makovtsev, G. A., KOSMICHESKAYA 
BIOL., No 4, 1978, pp 85-87. 


2. Sobolevskiy, V. I., “Effect of Sauna Baths on the Cardiovascular System 
and Work Capacity of Athletes," author abstract of candidatorial 
dissertation, Tartu, 1980. 


27 








6. 





Gromashevskaya, L. L., “Use of Functional Tests in Medical Monitoring 
and Therapeutic Physical Culture," Moscow, 1972, pp 17-18. 


Matei, M., SAUNA-NACHR., Vol 23, 1980, pp 1-5. 
Krauss, H., "Sauna Baths," Berlin, 1976. 


Katkov, V. Ye., “Dynamics and Regulation of Circulation in Orthostatic 
Position,” author abstract of candidatorial dissertation, Moscow, 1974. 


23 











UDC: 612.741.014.477-064 


EFFECT OF SEVEN DAYS WITHOUT GRAVITY LOAD ON VELOCITY AND STRENGTH OF 
HUMAN SKELETAL MUSCLES 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 10 Jun 82) pp 21-25 


[Article by L. S. Grigor'yeva and I. B. Kozlovskaya] 


[English abstract from source] By isokinetic dynamometry the 
effect of 7-day water immersion on the velocity-strength 
properties of the triceps and anterior tibial muscles was 
investigated. The exposure decreased significantly the 
maximum strength of the leg extensors (about 302%); this was 
seen in a large velocity range (60-180°/s) and during static 
movements. The decline of the contractile properties of the 
extensors was also manifested in a significant increase of 
the ratio of bioelectrical and mechanical effects of con- 
traction which was greatly pronounced during high-load 
(60°/s) and isometric regimens. The strength properties of 
the tibial muscle diminished only during isometric contrac- 
tions. The high rate with which the above changes developed 
and returned to normal after the exposure (3-5 days) are 
indicative of their reflex nature and association with 
mechanisms of tonic disorders due to the lack of support 
loading. 


[Text] It is known that weightlessness and exposure to conditions that 
simulate it are associated, in particular, with a decrease in force of 
muscular contraction manifested primarily in antigravity muscles [1-6]. The 
mechanism of these disturbances is related to development of muscular 
atrophy due to the "disuse" factor [5, 6]. However, analogous changes in 
muscular properties have also been noted after shoft-term exposure to 
weightlessness factors, when atrophic processes cannot yet be marked [7-9]. 
It is logical to assume that, at this first stage of adaptation to 

absence of gravity load, the decline of strength characteristics of anti- 
gravity muscles is attributable to other, more labile influences occurring 
via a mechanism of reflex reactions and triggered by elimination of support 
function. In this regard, it was deemed important to assess the quantita- 
tive effects of short-term absence of bearing load on velocity and strength of 
skeletal muscles related to a different extent to gravity counteraction 
function, and to subsequently compare them to the effects of weightlessness 
assessed by the same method. 


29 





Methods 


We tested the strength and velocity of the anterior tibial muscle (ATM) and 
triceps surae (TSM) by the method of isokinetic dynamometry on an isokinetic 
dynamometer, which permits quantitative evaluation and recording of moments 
of force when performing movements at a specified velocity. The angular 
velocity of motion in the ankle joint constituted 180, 120, 60 and 0°s during 
the tests. Thus, in the latter case, movement was isometric. Testing was 
performed with strict standardization of position. The subjects were on a 
cot, with the thigh and foot of the tested leg positioned so as to have a 
130-140° angle in the hip joint and 120-130° in the knee, and the axis of 

the ankle would coincide with the axis of rotation of the pedal on the 
instrument. With adherence to these conditions, movements in the ankle 

joint were performed mainly due to exertion developed by calf muscles. During 
the tests, the subjects flexed and supinated the foot with maximum possible 
force and amplitude. At each tested velocity they performed 5-6 movements. 
[sometric testing was performed at a 75° angle in the ankle for plantar 
flexion and 105° for dorsal flexion. The dynamographic parameters--force 
moments and goniogram--were recorded on the instrument recorder; the electro- 
myogram (EMG) of functioning muscles was recorded bipolarly with superficial 
electrodes, with a 2 cm distance between electrodes. Automatic integration 
of the electromyographic signal with a time constant of 90 ms [10-11] was 
used for quantitative evaluation of the EMG. In analyzing the data, we 
averaged the parameters of three similar movements perforwed with maximum 
force moment (for each velocity). We then performed group analysis by the 
method of comparing pairs (before and after exposure) and determination of 
reliability of differences using Student's criterion. 


We conducted this study with the participation of 12 healthy men 24 to 35 years 
of age. We tested the effects of brief absence of support function on the 
model of 7-day immersion hypokinesia [12] so that the weight of the body 

was uniformly distributed over the surface. Velocity and strength tests were 
made before, then on the lst and 3d day after immersion; on 4 subjects, we 

also made testes on the 5th and 7th days of the recovery period. 


“hesults and Discussion 


After immersion, all of the subjects presented significant decline of force 
parameters of the TSM (plantar flexion of the foot), in both the 

lynamic and isometric modes of contraction. As can be seen in Figure 1, which 
illustrates individual data for one of the tested groups, on the first post- 
immersion day, the maximum force moments that developed with plantar flexion 
in isokinetic and isometric modes presented a considerably lower amplitude 
than in the background period. The validity of this is confirmed by the 
results of statistical processing of data illustrated in Figure 2. As can 

be seen in Figure 2, immersion hypokinesia led to a statistically reliable 
(P<0.01) decrease of maximum moments for the TSM in all dynamic and static 
modes of contraction. The velocity-force function curve was notable for 

less steep build-up of maximum force moments with change from higher to 

lower velocity and isometry. However, analysis of relative changes in 

force properties revealed that the percentile decline was uniform over the 
entire range: at all velocities, the force moments decreased by 27-34%. This 


30 











was associated with virtually no change in force and velocity properties of 
AT; a statistically reliable (P<0.01) decline of force parameters, which 
constituted 21% on the average for the group, was demonstrable only in 
{sometric mode. 


(a) 








J —_—— -——- --- = eee” 


: haber en ee le i ae 
en fos PN Pe ON PN 


») = 


\ [ A ee NN I™.. 


/ 
(hb) 





000.LV | 


100 .. Inui 
4» /000mS 























Figure 1. Mechanical and bioelectric parameters of maximum voluntary 
contractions of TSM in isokinetic (a, 60°/s) and isometric 
(b) modes before immersion (I) and on the lst postimmersion 
day (II) (individual data) 


1, 2) electromyograms for ATM and soleus, respectively 
3) integrated (envelope) EMG of soleus 
4) goniogram of movements 
5) moments of forces developed during TSM contraction 


Figure 3 illustrates the distribution of cases where there were different 
degrees of change. A decline of force parameters for the posterior group 

of crural muscles was observed in all subjects, but to different degrees. 

The maximum of frequency of distribution (40-50%) with all modes of motion 
corresponded to about 30% decrease in force. On the whole, in the entire 
velocity range, the changes in strength perameters for the TSM after immersion 
were similar; however, in isometric mode (0°/s) there was maximum homogeneity 
of changes. 


Postimmersion distribution of changes in velocity and force properties of the 
ATM was different. In the velocity modes tiiis muscle was characterized by 
absence (in 40% of the cases) or insignificant (to 10%) change (in 20-302% of 


31 








- the cases). In isometric mode, the 

ay distribution curve shifted to the left, 
clearly demonstrating a decline of 

force parameters. The distribution maxi- 
mum corresponded to a 20% decline in 307 
of the cases and 30% decline in 257%. 





The changes in force properties of calf 
muscles were also manifested by a 
, change in proportion of mechanical ana 
bioelectrical effects of contraction: 
a on the lst postimmersion day, there 
was statistically reliable (P<0.01) in- 
a crease in correlation between maximum 
EMG amplitudes and exertion developed 
by the soleus in all tested modes 
0 50 120 780% s (Figure 4). The increase was signifi- 
cant, constituting a mean of 50 to 802, 
and was relatively more marked in the 
low-velocity (60°/s) and isometric 
modes. This was not associated with 
appreciable change in ATM parameters, 
and this correlation showed a statis- 
tically reliable increase only in 
isometric mode. 





Figure 2. 
Force-velocity parameters of calf 
muscles before and after immersion 
(average data on 12 subjects). 
X-axis, angular velocity of 
foot movements (°/s); y-axis, 
force moments developed (in Nem); 
white triangles, TSM before immer- 
sion, black--lst postimmersion 
day. Vertical segments indicate 
standard errors and asterisks-- 
statistically reliable 
differences (P<0.01). 


The force characteristics of TSM re- 
mained somewhat below base levels even 
on the 3d postimmersion day; their 
definitive recovery was observed only 

on the 5th day. The force parameters of 
ATM, which declined after immersion only upon isometric contraction, were 
already restored by the 3d day. 


Our study revealed that removal of bearing loads is associated with marked 
decline of force properties of antigravity muscles. The decline of calf 
extensor force after immersion, which was manifested in both velocity and 
isometric modes of contraction, reached 30-40% by the 7th day of immersion. 
The results of analyzing the EMG, which revealed a significant increase in 
correlation between electrical and mechanical effects of muscular contraction 
over the entire tested range after immersion, were also indicative of worsen- 
ing of contractile properties of extensors in this instance. It is known 
that elevation of this parameter is related to decline of functional capa- 
bilities of the muscular system [13, 14]. 


The speed of development of the demonstrated changes, as well as time of 
their correction upon termination of immersion (3d-5th day of recovery 
period), are indicative of their functional nature and confirm the hypothesis 
that the noted changes are reflex in nature. There is every reason to 

assume that mechanisms of tonic disturbances play the leading role in their 
development. It is known that stimulation of bearing zones is a specific 
trigger for postural tonic responses [15]. Elimination of bearing loads, 


32 

















which is associated with decline of excitatory tonic influx to extensor moto- 
neurons, causes a corresponding decrease of extensor tonus. Indeed, a de- 
crease in tonus of antigravity muscles following spaceflights and conditions 
that simulated them was noted by several authors [7, 8, 16]. Apparently, the 
tonic changes and related changes in elastoviscous properties of muscles 
could cause appreciahle disturbances in velocity and force properties of 


skeletal muscles. 










% a 
50 


o 





' 
* 4. iN 


7 4 
“90-20-10 0 +10*%+H 











d | % 
~$0-40-2)-20-10 0 - 40-90-20 -10 








Distribution of magnitude of changes in maximum moments of 














Figure 3. 
forces developed by calf muscles at different angular 
velocities of foot movements under the effect of 7-day 
immersion (mean data for 12 subjects). X-axis, magnitude of 
change (%); y-axis, relative frequency of changes (%); 
a-d) 0, 60, 120 and 180°/s, respectively. 
Figure 4. 
- Correlation between maximum EMG ampli- 
soleus 20; AT™ |] tude and developed force moments at 
Sal different velocities of movement before 
er ; and after immersion hypokinesia (mean 
10- 20 data for 12 subjects). 
at ° 18} X-axis, angular velocity of motion 
27 Al ; (°/s); y-axis, correlation between 
aa ain 7 amplitudes of EMG and force moments 
Qs dal - (in mV/kg-m); white bars--background, 
rat pal | black--lst postimmersion day. 
o! 02+ Vertical segments--standard errors, 
0 60 120 %0 C -z 120 BO asterisks--statistically reliable 


differences (P<0.01). 


33 


The changes in velocity and force properties of muscles deprived of support 
function showed a distinct dependence on the degree of their involvement 


in eutigravity function and contraction modes. The absence of support load 
hau a particularly marked effect on calf extensors in isometric and slow 
movements. This was indicated by the most significant increase in electro- 


contractile ratio in these modes. The velocity and force properties of the 
calf flexor (ATM) did not change or changed insignificantly when tested in 
dynamic modes after immersion. At the same time, in isometric testing modes, 
there was a significant decline of force capabilities of this muscle. Thus, 
the effects on muscles of lack of bearing load were manifested the most during 
movements, in which "tonic" motor units were greatly involved [17, 18]. 


On the whole, the direction, magnitude and distribution of changes caused 

by absence of gravity load in force and velocity properties of muscles 

were similar to those observed folle ‘ng short-term weightlessness [8, 9], so 
that we can assume that the mechanisms of their development are similar. 


BIBLIOGRAPHY 


l. Bazhanov, V. A., Sergeyev, V. A. and Mitin, V. V., in "“Nauchnaya konf. 
pamyati A. V. Lebedinskogo. Materialy" [Proceedings of Scientific 
Conference in Memory of A. V. Lebedinskiy], Moscow, 1965, pp 5-7. 


2, Genin, A. M., Sorokin, P. A., Gurvich, G. I. et al., in "Problemy 
kosmicheskoy biologii” [Problems of Space Biology], Moscow, Vol 13, 
1969, pp 247-253. 





3. Nefedov, Yu. G., Kakurin, L. I. and Yegorov, A. D., in "Kosmicheskaya 
biologiya 1 aviakosmicheskaya meditsina" [Space Biology and Aerospace 
Medicine], Moscow-Kaluga, Vol 1, 1972, pp 87-89. 


4. Yuganov, Ye. M. and Kopanev, V. I., in "Osnovy kosmicheskoy biologii i 
meditsiny"” [Fundamentals of Space Biology and Medicine], Moscow, Vol 2, 
Bk 2, 1975, pp 173-197. 


Pestov, I. D. and Geratevol', Z. D., Ibid, Bk 1, pp 324-369, 


6. Gazenko, 0. G. and Yegorov, A. D., in "Nauchnyye chteniya po aviatsii 
i kosmonavtike" [Scientific Lectures on Aviation and Astronautics], 
Moscow, 1981, pp 122-137. 


Bryanov, I. I., Yemel'yanov, M. D., Matveyev, A. D. et al., in 
"XKosmicheskiye polety na korablyakh ‘Soyuz’. Biomeditsinskiye 
issledovaniya" [Spaceflights Aboard Soyuz-Series Spacecraft. 
Biomedical Research], Moscow, 1976, pp 195-229. 


~ 
. 


8. Grigor'yeva, L. S., Gevlich, G. I., Kozlovskaya, I. B. et al., in 
"Vsesoyuznaya konf. po kosmicheskoy biologii i aviakosmicheskoy 
meditsine. 7~ya. Tezisy dokladov" [Summaries of Papers Delivered at 
7th All-Union Conference on Space Biology and Aerospace Medicine], 
Moscow-Kaluga, Pt 1, 1982, pp 111-112. 


34 





9. Kozlovskaya, I. B., Kreidich, Y. V., Oganov, V. S. et a’., ACTA ASTRONAUT., 
Vol 8, 1981, pp 1059-1072. 


10. Inman, V. T., Ralston, H. J., Saunders, J. B. et al., ELECTROENCEPH. 
NEUROPHYSIOL., Vol 4, 1952, pp 187-194, 


ll. Rosenfalck, A., in "International Conference Medical Electronics. 2d. 
Proceedings," London, 1960, pp 9-12. 


12. Shul'zhenko, Ye. B. and Vil'-Vil'yams, I. F., KOSMICHESKAYA BIOL., No 2, 
1976, pp 82-89. 


13, Vries, H. A., AM. J. PHYSIC. MED., Vol 47, 1968, pp 10-22. 


14. Bouisset, S., in "New Developments in Electromyography and Clinical 
Neurophysiology," Basel, Vol 1, 1973, pp 547-583. 


15. Magnus, R., "Body Stance,"’ Moscow-Leningrad, 1962. 


16. Kakurin, L. I., Cherepakhin, M. A. and Pervushin, V. I., KOSMICHESKAYA 
BIOL., No 6, 1971, pp 53-56. 


17. Burke, R. E., NEUROSCI. RES. PROGRAM. BULL., Vol 9, 1971, pp 60-85. 


18. Kozlovskaya, I. B., "Afferent Control of Voluntary Movements," Moscow, 
1976, 





35 








UDC: 612.766.2-08:612.17.014.2 
MORPHOMETRIC AND GRAVIMETRIC STUDY OF RAT HEART DURING LONG-TERM HYPOKINESIA 


Moucow KOSMICHESKAYA BIOLOCIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 1 Oct 82) pp 25-28 


(Article by A. S. Kaplanskiy, G. N. Durnova and Ye. I. I1'ina-Kakuyeva} 


[English abstract from source] Hearts of adult rats exposed 

to 30, 60, 90, 120 and 165-day hypokinesia were examined by 
histological, morphometric and massmetric methods. Prolonged 
hypokinesia delayed rat growth and terminated heart growth. 

\s compared to the controls, the delayed increase of the 

heart mass of hypokinetic rats was induced by the discontinued 
growth of cardiomyocytes. The growth of the right and the left 
heart was inhibited in a similar degree. 


[Text] At the present time it is a known fact that restriction of human 

and animal motor activity has an adverse effect on cardiovascular function 

and leads to development of myocardial deconditioning [1]. The structural 
changes in the myocardium under the effect of hypokinesia, which are the basis 
of the observed functional disturbances, have not been sufficiently investi- 
gated. In most works dealing with this problem [1-5], it is merely stated 
that there is a reduction in mass of the myocardium. Thus far, no morpho- 


metric studies of the heart had been conducted. Yet, as validly indicated 
7 Gnatyuk [6], “one can make a reliable assessment of the state of 

he myocardium only on the basis of a combined study using macrometric, 

micrometric, planimetric and gravimetric methods." We submit below the 


results of such gravimetric and morphometric studies of the myocardium 
t mitted to long-term hypokinesia. 


experiment was performed on 84 male Wistar rats weighing about 300 g. The 
inimals were divided into two equal groups--experimental and control. The 
‘xperimental group of rats were kept in special box-cages that restricted 
everely their mobility; however, the rats could still turn about their long 
body axis, take feed with their front paws and groom their snouts. The 
animals of the control group were kept under the usual vivarium conditions 
throughout the experiment. Both groups of rats received feed that was 
identical in quantity and quality, and water ad libitum. Before starting 


36 











the experiment, 10 intact rats were decapitated to serve as the base (back- 
ground) control. The experimental and control groups of rats (6-12 animals in 
each) were sacrificedwith ether 30, 60, 90, 120 and 165 days after the start 
of hypokinesia, and we weighed their body and heart. The entire heart was 
fixed in 10% neutral formalin, then a layer, 2-3 mm in thickness, was excised 
perpendicularly to its long axis, which included both ventricles, the septum 
and papillary muscles. The excised layer of the heart was embedded in paraffin. 
Heart sections, made perpendicularly to its long axis, were stained after 
removal of paraffin with hematoxylin and eosin, iron hematoxylin according to 
Heidenhain and picronigrosin according to Friborn [7]. Heart sections fixed 
with formalin were prepared on a freeze microtome and stained with oil-soluble 
red 0 for demonstration of Lipids. 


Fulton's index [8], which is the ratio of mass of left ventricle and septum 

to mass of right ventricle, was determined in order to obtain objective data 
about the effect of hypokinesia on the right and left heart of rats. However, 
in this experiment we used ready histological preparations of transverse 
sections of the heart, which were projected on standard paper using a photo 
enlarger, where we used a pencil to outline the right ventricle and left 
ventricle with septum, then cut out the patterns and weighed them on a torsion 
balance, unlike the conventional method, which is based on separate weighing 
of the heart for determination of Fulton's index. 


We selected the papillary muscles of the left ventricle as the object for 
morphometric studies of cardiomyocytes, since most of the cardiomyocytes in 
these muscles present the same longitudinal arrangement in one direction. 
Transverse sections of papillary muscles, which were stained with picronigrosin 
(a technique which permits good demonstration of cell outlines), were photo- 
graphed at 400 magnification and the negative images of cardiomyocytes 

were projected on paper using an enlarger; the patterns of 50 cells from 
different parts of the muscle were outlined with a pencil, cut out, weighed 
on a torsion balance and the obtained figure was divided by 50. Thus, we 
ultimately determined the mean cross section area (CSA) of one cardiomyocyte 
expressed in arbitrary units. All of the digital data were submitted to 
statistical processing by the method of confidence intervals with p<0.05. 


Results and Discussion 


As can be seen from the data illustrated in the Figure (a), there was progres- 
sive weight gain by rats of the control group throughout the experiment, 

which occurred unevenly, and periods of intensive growth (lst-30th and 120th- 
L65th experimental days) alternated with periods of insignificant weight gain 
(30th-120th days of the experiment). The body weight of experimental rats 

was lower for the first 60 days of hypokinesia than the base level. Subse- 
quently, as the rats adapted to hypokinesia this parameter began to gradually 
rise and, on the 90th day of hypokinesia, it reached the base level, remaining 
unchanged thereafter to the end of the hypokinetic period. Thus, the findings 
were indicative oi! the fact that prolonged restriction of movement leads to 
inhibition of growth. Analogous inhibition of animal growth under hypokinetic 
conditions had been repeatedly reported by many authors, who related it to 
development of stress, impairment of protein synthesis, intensification of 
catabolic processes and dehydration of the body [3, 9-14]. 


3/ 





The changes in heart mass in experimental 
and control groups of rats are illustrated 
in the Figure (b). In the control group, 
increase in heart mass paralleled the 
increase in body mass, as a result of 
which the relevant curves are similar 

in this figure (a and b). In the experi- 
mental group of rats, heart weight re- 
mained unchanged throughout the hypo- 
kinetic period and corresponded to that 
of rats sacrificed before the start of 








mz (b) the experiment (background control). On 
1 B00 - the whole, the weight of the heart was 
1 700 | substantially lower during 165-day hypo- 


kinesia (with the exception of the 30th 
1600 | day) than in control animals, and it 




















1500 | / must be emphasized in particular that 

1400) | hypokinesia did not lead to myocardial 
atrophy, rather it merely elicited 

coed | arrest of heart growth. The absence of 

1200 changes in Fulton's index, which consti- 

100} } i tuted 3.5-3.7 in both experimental and 
é-~ ~~ | “i p——42 control rats, is indicative of uniform 

000 | ie inhibition of development of the right 

900 + and left heart in hypokinetic rats, 

200 } which is consistent with the findings 

wal nein - of other authors [4], who also failed 





to demonstrate changes in the ventricular 

AN (c) ! index of rats whose motor activity was 

| restricted. These data indicate that, 
| although there is redistribution of 

j blood in hypokinetic rats [15], there is 

v4 no development of marked hypertension 
in the pulmonary circulatory system or 
hypertrophy of the right ventricle. 












cardiomyocytes of papillary muscles of 

the left ventricle are illustrated in 
a: a , - — the figure (c). It is apparent from 

these data that the CSA of papillary 

muscle cardiomyocytes in the control 
group of rats increased up to the age 
of 100 days (30th experimental day), 
after which it remained unchanged to 
the age of 8 months (165th experimental 
day). In other words, the impression is 
gained that the process of development 
of rat cardiomyocytes is concluded by 
the end of the 3d month of life, when 
the dimensions of the cells reach 
values inherent in adult animals. Growth of cardiomyocytes stopped somewhat 
earlier than stabilization of myocardial weight, and this conforms with the 


T 
' 
7™ TT The results of morphometric studies of 
i 


Changes in mass of body (a) and heart 
(b), as well as area of cardiomyocyte 
in cross section (c) in hypokinetic 
rats 
X-axis, duration of experiment (days) 
1) control 
2) experiment 
AU) arbitrary units 


38 














data in [16], to the effect that the increase in size of myocardial cells ends 
before discontinuation of cell reproduction, which is what causes the increase 
in myocardial mass. 


In the experimental group of rats (see Figure, c), the CSA of cardiomyocytes 

of the left ventricular papillary muscles remained unchanged from the beginning 
to the end of the hypokinetic period, being the same as CSA of cardiomyocytes 
in control rats sacrificed before the experiment (background control), and it 
was considerably lower than in the control. 


To sum up the foregoing, one should consider that hypokinesia leads to inhibi- 
tion of rat growth and arrest of heart growth, and the lag of myocardial mass 

in experimental rats, as compared to control animals, is related to arrested 
growth of cardiomyocytes. Other authors have arrived at an analogous conclusion 
[17} on the basis of studies of the heart of hypokinetic guinea pigs. 


BIBLIOGRAPHY 
Kovalenko, Ye. A. and Gurovskiy, N. N., "“Hypokinesia," Moscow, 1980. 
2. Gordiyenko, V. M., ORTOPED. TRAVMATOL., No 11, 1962, pp 68-72. 
3. Kuznetsov, V. I. and Pruss, G. M., in "Aktual'nyve problemy kosmicheskoy 
biologii i meditsiny” [Pressing Probiems of Space Biology and Medicine], 


Moscow, 1980, pp 57-58. 


4. Prokhazka, I., Khavkina, I. V. and Barbashova, Z. I., FIZIOL. ZH. SSSR, 
No 8, 1973, pp 1237-1241. 


Karupu, V. Ya. and Feicnts, A. I., in “Meditsinskiye problemy fizicheskoy 
kul'tury" [Medical Problems of Physical Culture], Kiev, Vyp 4, 1974, 
pp 78-83. 


~/* 
. 


6. Gnatyuk, M. S., KARDIOLOGIYA, No 12, 1978, pp 115-117. 
/. Romeys, B., "Microscope Engineering [or Techniques]," Moscow, 1954. 
8. Lifshits, A. M., ARKH. PAT., No 6, 1981, pp 24-30. 


9. Biryukov, Ye. N., Kakurin, L. I., Kozyrevskaya, G. I. et al., 
KOSMICHESKAYA BIOL., No 2, 1967, pp 74-79. 


10. Portugalov, V. V., Gazenko, 0. G., Il'ina-Kakuyeva, Ye. I. et al., 
Ibid, No 6, pp 18-25. 


ll. Potapov, A. N., Ibid, No 2, 1972, pp 16-20. 


12. Kovalenko, Ye. A., Mailyan, E. S., Popkov, V. L. et al., USPEKHI 
FIZIOL. NAUK, Vol 6, No 3, 1975, pp 110-136. 


13. Fedorov, I. V., KOSMICHESKAYA BIOL., No 3, 1980, pp 3-10. 


39 








14, Chernov, I. P., KOSMICHESKAYA BIOL., No 3, 1980, pp 57-60. 


15. Kovalev, 0. A., Lysak, V. F., Severovostokova, V. I. et al., Ibid, 
pp 60-64, 


16. Zyss, R., Krol, J. amd Kus, E., ACTA MED. POL., Vol 19, 1978, pp 289-303. 


17. Sands, J., Dobbing, J. and Gratrix, C. A., LANCET, No 8141, 1979, 
pp 503-505. 





40 











UDC: 612.766.2-08: [612.42+612.438] .017.1 


LYMPHOID ORGANS OF MONKEYS SUBMITTED TO ANTIORTHOSTATIC HYPOKINESIA 
(EXPERIMENTAL MORPHOLOGICAL STUDY) 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 9 Aug 82) pp 28-32 


[Article by G. N. Durnova and A. S. Kaplanskiy] 


{English abstract from source] The histological study of the 
thymus, spleen and inguinal lymph nodes of monkeys exposed to 
head-down tilt (-6°) for 7 or 19 days showed that the exposure 
caused an acute stress that resulted in the thymus involution 
and hypoplasia of the lymphoid tissue of the spleen and lymph 
nodes. The exposure produced fluid redistribution due to which 
the spleen blood content decreased and the mass of inguinal 
lymph nodes increased. This was induced by partial pooling 

of the lymph flowing from the lower extremities. The exposure 
also led to autoimmune developments. 


[Text] The results of clinical immunological observations indicate that 
long-term hypokinesia leads to decline of resistance to infection, impairment 
of immunobiological reactivity and allergization of the body [1-6]. The ad- 
verse effect of hypokinesia on the immunological status of the organism 
logically raises the question of need for further in-depth investigation of 
this phenomenon and, in particular, the state of immunocompetent (lymphoid) 
organs, in which the main immunomorphological reactions develop, which lead 
to onset of immunity. It is of special interest to investigate immunocompe- 
tent organs of primates submitted to antiorthostatic [head-down] hypokinesia 
(AOH), which is used extensively at the present time to simulate some effects 
of weightlessness on the ground. The data obtained from experiments on 
monkeys could, with some stipulations, be extrapolated to man. 


Methods 


The thymus, spleen and inguinal lymph nodes from 9 experimental male 

Macaca mulatta monkeys, which were kept under AOH conditions and 5 control 
monkeys of the same species, sex and age, kept in cages or pens, served as 
material for our study. We induced AOH in experimental animals by immobiliz- 
ing them in horizontal position on special cots using a method developed at 
the Institute of Experimental Pathology and Therapy, USSR Academy of Medical 
Sciences [7]. For the first 7 days of the study, the monkeys were submitted 


4) 








to clinostatic hypokinesia and for the next 12 days, to AOH at an angle ot 
-6” The first experiment was performed on 2 experimental and 2 control 

monkeys weighing about 5 kg and the second one, on 3 experimental and 3 
control animals with initial weight of 3 to 4.4 kg. In addition, in the 
second experiment, we studied the lymphoid organs of 2 monkeys with base 
weight of 3.3 kg, which were kept under AOH conditions for 7 days without 


prior clinostatic hypokinesia. 





Figure 1. Spleen of monkey submitted to AOH. Hematoxylin and eosin 
stain; objective 3.5*, ocular /*. 
) lymphoid follicles with large clear centers in spleen of control 
monkev 


4+) atrophy of lymphoid follicles in spleen of monkey after /-day AOH 


experimental and control group monkeys were sacrificed by intravenous injec- 


tion of 2-3 mz 10% hexenal, which led to instant death of the animals. 


Necropsy was started 10 min after death. The lymphoid organs were weighed, 


fixed in Carnoy's fluid, neutral formalin and imbedded in histoplast. Sec- 
spleen and lymph nodes were stained with hematoxylin and 


tions of the thymus, 
eosin, methyl green--pyronine, picrofuchsin according to Van Gieson and by 
the Perls method for iron. An MOV-15 ocular micrometer was used to determine 





the diameter of lymphoid follicles of the spleen and their clear centers (these 
parameters were measured in 20 follicles from each spleen) on spleen prepara- 
tions stained with hematoxylin and eosin. Because of the small number of 
experimental and control animals in both experiments, we did not submit the 
obtained data to statistical processing. 


Results and Discussion 


Thymus. The results of weighing the thymus (see Table) indicate that AOH 
elicited marked atrophy of the thymus in the absolute majority of monkeys. 
The most drastic differences in thymus weight between the experimental and 
control groups of monkeys were observed in the second experiment, in which 
younger animals were used. The high sensitivity of the thymus of young 
monkeys to the stressor effect of AOH is perhaps attributable to the fact 
that it contains a larger number of cortisone-sensitive lymphocytes than 
the thymus of adult animals that has undergone age-related involution. 


Mass of lymphoid organs of monkeys submitted to AOH at an angle of -6° for 
7 and 19 days 





——- 


























| j WEIGHT OF LYMPHOID ORGANS, G 
EXPERI~ | EXPERIMENTAL | q 
MONKEY | INGUINAL 
MENT CONDITIONS THYMUS SPLEEN LYMPH 
ane T + —————— a PT 

i | eiRrstT VIVARIUM een | 0,270 5,850 1,000 

2 0,650 7,050 0,500 

3 19-DAY AOH INOT DEMONSTRABLE 3,200 | = 0,690 
| MACROSCOPICALLY | 

4 SAME 4,850 1,900 

a eee j—____— : : 

5 VIVARIUM CONTROL | 4,100 ee | 9,200 

6 2,650 3,340 0,320 

7 SECOND | 2,050 | 2,970 0, 30 

% | 19-DAVY AOH ‘NOT DEMONSTRABLE 3,35) 0,350 
| | MACROSCOPICALLY | 

9 SAME | 2,870 0,600 

10 > > | 4,120 0,450 

11 7-DAY AOH > » ; 2,120 0,420 

12 2,950 3,000 0,420 
' 





| 
| 
| 


i 





Histological examination of the thymus revealed that acute accidental involu- 
tion of the gland, which developed in monkeys submitted to AOH for 7 and 19 
days, differs morphologically from the slow growth-related involution of 

the thymus and that the changes observed in the thymus of monkeys in the 
experimental group are similar, though they varied in intensity. After AOH, 
most of the thymus tissue was replaced with fatty and connective tissue; 

the intact lobes of the thymus were small, and it is by far not always that 
they retained their typical structure, with subdivision into cortical and 
medullary substance; the cortical substance of thymus lobes was markedly 
reduced, with vague or no boundary between it and the medullary substance; 
there was significant increase in number of Hassall's corpuscles per unit 
area of medullary substance; there were focal collections of plasma cells in 
the corticomedullary zone or, if none was demonstrable, over the entire 


43 





lobule; there were trabeculae of young connective tissue proliferating into 
the lobules from the periphery, as well as groups of fat cells, in the sub- 
capsular parts of the lobules; the interlobular connective tissue layers 
were thickened, demonstrating plasma and mast cells in some places, 

















Figure 2. Lymph node of monkey submitted to AOH. Hematoxylin and 
eosin stain; objective, "Microplanar" 1:4.5, F = 65 
) general view of inguinal lymph node of monkey submitted to AOH for 
/ days; numerous markedly dilated vessels filled with lymph can be 
seen in the region of the Lymph node hili 
“) fragment of same lymph node at greater magnification: dilated 


‘ 


lymphatics 


demonstrating lymphostasis 


yleen. As can be seen from the data listed in the Table, some reduction 
of spleen mass was observed in 2 monkeys after 7 days of AOH (second experi- 
and 2 monkeys after AOH for 19 days (first experiment), whereas no 


ment ) 
ilso submitted 


reduction of spleen weight was demonstrable in 3 other monkeys 
to AOH for 19 days (second variant), as compared to control values. 














Histological examination of the spleen of all monkeys submitted to AOH re- 
vealed reduction of delivery of blood and neutrophil infiltration of the red 
pulp. In addition, the latter consistently demonstrated large and small 

focal collections of predominantly mature plasma cells in experimental mon- 
keys. There were no plasma cells in the spleen of control monkeys, or else 
they were encountered in small quantity. A decrease in dimensions of lymphoid 
follicles and their clear centers was observed in 2 monkeys after /-day AOH 
and in 2 others after 19-day AOH (first experiment), and the recuction in 
dimensions of the clear centers corresponded to the decrease in number of 
dividing cells in them with pyroninophilic cytoplasm (Figure 1, a and b). 
Thus, the impression is formed that the reduction in weight of the spleen of 
some experimental monkeys is correlated with hypoplasia of white pulp. At the 
same time, no reduction in dimensions of lymphoid follicles of the spleen and 
their clear centers was observed, as compared to the corresponding control, 

in monkeys used in the second experiment, which were also submitted to AOH, 
and they presented an active proliferative process in the clear centers. 


Inguinal lymph nodes, According to the data listed in the Table, in both 
the first and second experiments all of the experimental monkeys showed a dis- 
tinct tendency toward increase in weight of lymph nodes. Histological examina- 
tion of the lymph nodes of all animals submitted to AOH yielded the impressive 
finding of markedly dilated lymphatics (Figure 2, a and b) and sinuses, with 
numerous macrophage elements, vacuolized cytoplasm and a moderate number of 
lymphocytes; no proliferation or desquamation of sinus endothelium was ob- 
served. In the medullary trabeculae of lymph nodes of experimental monkeys, 

we found intensive plasma cell hyperplasia extending, in a number of instances, 
to the paracortical region as well (Figure 3). The cortical substance of 

lymph nodes was constricted, the follicles reduced in size, with small and 
inactive clear centers (dividing cells and immature pyroninophilic cells were 
encountered only in a few clear centers). A comparison of the results of 
weighing lymph nodes to results of histological analysis leads us to conclude 
that the increase in mass of inguinal lymph nodes of monkeys submitted to AOH 
is related primarily to deposition of lymph in them due to intensive efflux 
from the lower extremities, as well as development of plasma ceil hyperplasia 
in them. 


We can divide the changes that occur in lymphoid organs of monkeys submitted 
to AOH into three categories, according to their genesis. The first category 


is referable to acute involution of the thymus and hypoplasia of lymphoid 
tissue of the spleen and lymph nodes. These changes are apparently due to 
development of an acute stress reaction induced by immobilization of the 
animals. The observations of other authors [8, 9] are also indicative of 
development of acute stress in monkeys submitted to hypokinesia for 1 week. 
By the end of the 19th day of AOH there is probably partial adaptation to 
new living conditions. Restoration of weight and dimensions of lymphoid 
follicles of the spleen, as compared to monkeys submitted to AOH for 7 days 
(second experiment) confirms this assumption. 


Development of stress when animals are submitted to AOH is instrumental in 
"movement" to a new functional level of the systems responsible for develop- 
ment of the systemic adaptation syndrome, as a result of which the animals 


45 





react rapidly to a repeated 
stress factor, in particular 
the manipulations that pre- 
ceded sacrificing them (taking 
the EKG, rigid immobilization 
on a board, transfer to a 
different room, etc.). The 
fact that there was time for 
development of neutrophil in- 
filtration of red pulp of 

the spleen, which is one of 
the morphological signs of 
acute stress, is also indica- 
tive of the validity of the 
above hypothesis, whereas no 
neutrophil infiltration of the 
spleen was demonstrable in 
control animals that were sub- 
mitted to the same manipula- 
tions. 


In the second category of 
changes in lymphoid organs of 
monkeys submitted to AOH are 
changes related to redistri- 
bution of body fluids. Thus, 
the decreased delivery of blood 
to the spleen of monkeys sub- 
mitted to AOH correlates well 
with the results of studies 
made by other authors [10], 
who demonstrated, using a 
radioisotope technique, that 
there was a percentile reduc- 
tion in blood content of the 
pleen in the course of /7=- and 30-day clinostatic hypokinesia. The increase 
weight of inguinal lymph nodes, apparently caused by partial deposition 
lymph in them due to intensified efflux from the lower extremities, is 
ilso indicative of redistribution of body fluids under AOH conditions. 





Figure 3, 
Hyperplasia of plasma cells in medullary 
trabeculae of inguinal lymph node of a 
monkey submitted to AOH for 19 days 
Hematoxylin and eosin strain; objective 
16x, ocular 7* 





Finally, we should include in the third category of changes the “plasmatiza- 
tion" of the spleen and lymph nodes, which is the morphological expression of 
i fully developed immune reaction and is indicative of active antibody synthesis. 
ince the monkeys used in our experiments were in good health and they were 
not given any agents with antigenic properties, the presence of plasma cell 
hyperplasia in the spleen and lymph nodes can be interpreted as a manifestation 
f an autoimmune process arising due to sensitization by products of tissue 
»reakdown, which occurs under hypokinetic conditions. Appearance in rat blood 
‘f antibodies against muscle tissue antigens [11] is indicative of activation 
»)f autoimmune processes under hypokinetic conditions. 


Thus, the results of our study revealed that changes develop in lymphoid 
(immunocompetent) organs of monkeys submitted to AOH, which cannot fail to 


46 








affect the immunological status of the organism and, apparently, are the basis 
of depression of its immunobiological reactivity. In our opinion, onset of 
the autoimmune process merits special attention. 
BIBLIOGRAPHY 
l. Sorokin, P. A., Simonenko, V. V. and Korolev, B. A., in "Problemy 
kosmicheskoy biolugii” [Problems of Space Biology], Moscow, Vol 13, 1969, 
PP 24-34, 

2. Chukhlovin, 3. A. and Burov, %. A., Ibid, pp 115-121. 

3. Krupina, T. N., Mikhaylovskiy, G. P., Tizul, A. Ya. et al., in 
"Adaptatsiya k myshechnoy deyatel'nosti i gipokinezii" [Adaptation to 
Muscular Activity and Hypokinesia], Novosibirsk, 1970, pp 94-96. 

4, Parin, V. V. and Krupina. T. N., Ibid, pp 134-136. 


5. Chukhlovin, B. A., Ostroumov, P. B. and Ivanova, S. P., KOSMICHESKAYA 
BIOL., No 6, 1971, pp 61-65. 


6. Ostroumov, P. 8. and Chukhlovin, B. A., in "Immunoreaktivnost' organizma" 
[Immunoreactivity of the Body], Kaliningrad-Tallin, 1973, pp 85-86. 


7. Urmancheyeva, T.G. and Dzhokua, A. A., KOSMICHESKAYA BIOL., No 5, 1980, 
pp 82-84. 


8, Mason, J. W., AM. J. PHYSIOL., Vol 222, 1972, pp 1291-1294. 


9, Mason, J. W., Mongey, E. H. and Kenon, C. C., PHYSIOL. BEHAV., Vol 10, 
1973, pp 801-804. 


10. Kovalev, 0. A., Lysak, V. F., Severovostokova, V. I. et al., 
KOSMICHESKAYA BIOL., No 3, 1980, pp 60-64. 


ll. Portugalov, V. V., Ivanov, A. A. and Shvets, V. N., Ibid, No 2, 19/6, 
pp 84-86. 


47 








UDC: 629.78:612.351.11-08 


EFFECT OF SPACEFLIGHT ABOARD COSMOS-1129 BIOSATELLITE ON ENZYME ACTIVITY IN 
RAT LIVER 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 28 Oct 82) pp 33-37 


[Article by S. Nemeth and R. A. Tigranyan (CSSR, USSR) } 


[English abstract from source] After the 18.5 day Cosmos-1129 
flight the activity of 7 glucocorticoid-stimulated enzymes of 
the rat liver was measured. Immediately postflight the activity 
of tyrosine aminotransferase, tryptophan pyrolase and serine 
dehydrogenase increased. These enzymes rapidly (within 

several hours) react to increased glucocorticoids. The activity 
of aspartate and alanine aminotransferases also increased. 

These enzymes require many days of a continuous effect of gluco- 
corticoids. The glycogen concentration in the rat liver also 
grew. At R+6 the activity of tryptophan pyrolase and serine 
dehydrogenase decreased and that of the other enzymes returned 
to normal. The immobilization stress applied postflight led to 
an increased activity of tyrosine aminotransferase and tryptophan 
pyrolase. This study gives evidence that after space flight 
rats are in an acute stress state, evidently, produced by the 
biosatellite recovery. 





[Text] It is known that administration of glucocorticoids is associated with 
increase in activity of several enzymes of the rat liver; there is very 

rapid increase, within several hours, in activity of tyrosine aminotransferase 
(TAT, EC 2.6.1.5), tryptophan pyrrolase (TP, EC 1.13.1.12) and serine 
dehydratase (SD, EC 4.2.1.13), and their half-life is equally short, whereas 
many days of exposure to glucocorticoids is required for increase in activity 
of aspartate aminotransferase (AST, EC 2.6.1.1), alanine aminotransferase 
(ALT, EC 2.6.1.2), fructose-1,6-diphosphatase (FfpPp, EC 3.1.3.11) and glucose- 
6-phosphatase (G6P, EC 3.1.3.9). 


It has been shown that the activity of hormone-induced enzymes in the liver 
also increases under the effect of stress. Thus, with single exposure to 

immobilization stress, an increase was noted in TAT [2] and TP (3) activity, 
and it was demonstrated that, with this form of stress, TAT and TP activity 
is increased only by glucocorticoids [4]. At the same time, in the case of 


48 








recurrent stress, there is increase in activity of AST and ALT, which require 
long-term influence of hormones; in rats submitted to adrenalectomy, there is 
no increase in activity of the above-mentioned enzymes, and this confirms the 
role of glucocorticoids in this reaction [1]. 


[hese data indicate that enzymes, the activity of which increases rapidly, 
are good indicators of acute stress, whereas activation of enzymes that 
require long-t »m exposure to glucocorticoids is indicative of the presence 
of chronic stress. We used these theses in our studies aboard biosatellites 
of the Cosmos series. It was demonstrated that there was considerable in- 
crease in TAT and TP activity, with concurrent mild increase in AST activity 
in the rat liver following a 19.5-day flight aboard Cosmos-/82, whereas 
activity of SD, ALT, FDP and G6P did not undergo noticeable changes [5]. At 
the same time, after termination of the 18.5-day spaceflight aboard Cosmos- 
936, significant increase was noted in TAT and TP activity of the rat liver, 
with concurrent increase in activity of ALT, AST, FDP and G6P in rats sub- 
mitted to weightlessness; there were no changes in activity of the tested en- 
zymes in rats exposed to artificial gravity during the flight [6, 7]. 


Our objective here was to study the activity of the above-mentioned hormone- 
induced enzymes in the rat liver in order to determine the nature of the 
stress reaction associated with spaceflights, as well as to assess the meta- 
bolic effect of possible glucocorticoidemia during the flight period. 


Methods 


These studies were conducted on male Wistar-SPF (Bratislava, CSSR) rats, 

which were flown in space for 18.5 days aboard Cosmos-1129 biosatellite. The 
animals were decapitated 6-8 h after landing and on the 6th postflight day, 
and some of .he animals decapitated on the 6th postflight day, as well as rats 
in the corresponding control and synchronous groups, were submitted to 5-fold 
immobilization stress daily for 150 min each day. Enzyme activity was 
determined in a homogenate (G6P [8]) or supernatant after centrifuging at 
15,000 G (TAT [9], TP [10], Fpp [11], SD [12], AST and ALT [13]). In addi- 
tion we assayed glycogen concentration in the liver [14! and protein in the 
incubated material [15]. The special food allowance is described in [6]. 


Results and Discussion 


Immediately posfiight, the animals presented an increase in TAT, TP and SD 
activity (scaled t ‘nzyme activity per gram liver protein); ALT activity was 
elevated both in flight rats and animals in the corresponding synchronous 
group; FDP and G6P activity (the latter in the synchronous control also) was 
jiminished in comparison to the vivarium control (Table 1). When enzyme ac- 
tivity was scaled to 1 g body weight (Table 2), flight animais presented an 
increase in TAT, TP and SD activity, as compared to both control groups of 
rats, increase in AST and ALT activity (as compared to the vivarium control) 
and decrease in G6P activity; in rats used in the synchronous experiment, 
there was an increase in TAT and ALT activity, with decrease in G6P activity. 


Six days after landing, the flight animals presented a decrease in TP and SD 
activity (as compared to the vivarium control) and increase in FDP activity 


49 








(as compared to synchronous control); the activity of the other enzymes 
tested did not differ from activity in vivarium control rats (see Tables ] 


fable 1. Activity of liver enzymes scaled to l g protein (Mtm) 


- - ——— = - ee - — —_—_ —— -—- - " - _ — _ 





Parameter Group ! 

















-——_— oe cr =- -——_——_o_ a —— — - _ 
; | 
| C€ 11,04 0,6 | 13,8+0,6 19, 6-+1,' 
AT, wmol/g/min | 11 ,.7+6,59.5 | 4,241.3 | 5,5+5,4 
17,9+ 1,9" 13,8+0,8 Aol + 3,8" 
re Soe SY C | 4.5 4 0.5 b ry ‘ | 19 9 1s 
a da g/ 4 k 64-0,9 9 4.4.() 5A | RG » 4° 
ed ~ - 
S | 4440.2 | 2540.5 | 9,9+ 1,5" 
| 
/ 1/mir S | 19,6 2,0 15,6 o,3 | 16,1 7 7 
' A/ g/min F 37, 144,78 4), 1+ 2.3 | 10.64.5.9 
2 | 2 9 ba 2 ie) ue rs ° fy 4 7 
’ P - | | “ ‘ 
> , / = | + 404 4 ] ; i t ».9 42 ' jad } +} P 
; , ; 4 3/1 a4 Ib 174 5 4) . 0 15% JOR & 47 Q 
| . ‘ 4 - o 
| 2 417,44 20,1 G5 4+54,5 | 05,1 31,6 
, | A C 113 +89 | 131 64 | } , ‘+ 19 
4 , 4 f J ‘d 3/min f icon 9 r : 9 ) ~ a 
I 4 152,34 14,3 ale. ~2Z a j ] 1k 19,5 
2 l5A,34 28 166.2 3,74 | 190.34 25,0 
Jen Jf | ( 174,6+46,5 19] 4419,0 202,3 5,2 
, i G/i i fi k 152.64 »,9* 91? + 10) BO | 10 ,.2 : 14 ty 
~) 165,94 11,1 175,74 10,3 179,7+7,0 
| 
, | C 164,945, | = 145,2+9,3 155,3+5,4 
, vas ys mee i 126,6+-7,1* 159,14-9,4 139,34-5,6 
S 119,14-4,1* IS), bai 132,9+9,8 
eae SS ee Sr 
Key for this, Tables 2 and 3: 
C) vivarium control 
) flight 
ynchronous experimen’ 
6-, h after landing 
6ti postlanding day 
6th day after landing + immobilization stre 
1,6) reliability of differences as compared to C and sroups, respectiveiy 
B) reliability of differences when comparing groups 3 and 2 
ever, when the rats were submitted to repeated i’ ilizatior tress, alfter 
ays we demonstrated only an increase in TAT and TI ctivity, and this was 
th in flight animals and those of both control frou © Tables |! 
¢ } 
mediately after the experiment, the flightand synchronous group animals 
r nted a reduction (as compared to vivariu ontroi) in body weight and 
rotelr ncentration, and an increase in ; ogen content, mass of the 
r of flight animals was increased, as compared to both control grout 
ifter landing, the flight animals ill weighed less than thos¢ 
yarium control. In rats submitted ¢t fold imme lization stre 
e recovery period, 6 days after the flight, there ' 1 decrease in 
tration of glycogen and weight of the liver in animals of the flight 
synchronous groups, as well as decrease in weight rat n all teste 








fable 2. Hepatic enzyme activity scaled to 1 g body weight (M m) 


- —-- 7 Se ee = ee ne 0 oe 

















s — 
Parameter | Grou} i 2 | ' 
+—— pg 
| 
TAT, wmol/g/min C 0.047+0.003 0,054 +0,003 (.142+-0,008" 
F 0,2294+0,034,6 1 048 4-0,003 | 0,124+0,027" 
S 0,0754.0,0088 | 0,048 0,003 | 0,123+0,012" 
TP, wmol/g/h | 0.0154 0,002 0.015+0,002 | 0,048+0,006" 
| 0,025-+0,0044 6| 0.008--0.0014 0.031 +-0,009" 
| S 0.014+0,001 | 0,009+0,002 | 0,032 +0,005" 
ne . 1/a/ 0,054 +0,009 0,173.4-0,024 0,164+0,021 
0, Ymvs/9/man | &£ 0,163+0,0199.6] 0,1044-0,011" 0,130+0,013 
S | 0,108+0,010 0,190+0,024 | 0,1044-0,0144 
AST. umol/ - | ,30-+0,09 1,034+0,120 | 1,172+0,146 
AST, wmol/g/min F | 1,650.13" 0,848-4.0,119 1044+0,123 
S 1,334-0,07 0,994+0,155 0,972+0,086 
den f C 0,48440,047 0,922+-0,114 0,737+0,051 
ALT, \mol/g/min F 0,674+ 0,056" 0,647+0,081 0,629+ 0,065 
S (0),646+0,037" 0,583.+-0,14) 0,608+0,073 
CoD . l a / . 0,7494 0,054 ( .74340,069 0,727 + 0,063 
FDP, ymol/g/min F 0682+ 0,036 0,734 +-0,037 0,645+ 0,038 
| S | 0,691+0,038 0,612+0,038 0,579+0,031 
| Cc | 1,055+0,030 0,979-+-0,057 0,933 +0,050 
GOP, \wmol/g/min F 0,856+0,0324 0,957+0,072 0,514+0,066 
S 0,8014-0,0404 (,895+-0,061 ),727+0,054 





Table 3. Rat weight, liver weight, protein and glycogen content of liver 








(Mm) 
ccna reel —_ ee 
Parameter | Group | i 2 3 
ee 
TT -_-—- 4 ’ 
Body We] gnt , C | 359 + 4,6 | i+ 9.2 A7T+ 2,4° 
| | 420+ 3,5" 345+6,8" 319+ 5.9%." 
S | 336+ 6,7? $644+9,3 330+ 4,5°." 
’ ; 11,7+0,3 | 12,6+0,7 11,9+0,4 
Liver weight, g | F 13,140,3%6 | 11,7+0,2 9,9+0,8%." 
S 12,14-0,2 12,1+0,6 9.440,34,8 
Drntoir oe wet é |] 7 + 44 lo.64 4% 106.2 4,4 
r fo atly /3 FE 112,141.48 | 101,6+6,9 109, 8+ 5,2 
ilver S 116.4 ° },7* | 105.64 38 114.6 +59 
24,44.4,7 | 49,24 10,2 32,1+9,1 
i Tl, wet } » | : 4 | 97 8+6,7 21,4+8,9" 
live? iss : 74943 98 49.9462 9.04-0,354.9 


“ — - - “ — - _— -- <= - _— —- —— —_—-+---<- 


7 


These studies revealed that, immediately after the flight, the flight animals 
showed an increase in hepatic enzymes that require brief exposure to 
glucocorticoids--TAT, TP and SD. This is indicative of the presence of 
acute stress, which was apparently related to landing of the biosatellite. 
The increase in AST and ALT activity is indicative of chronic hypercortico- 
steronemia (i.e., presence of chronic stress). An increase in TAT and ALT 
activity was also demonstrated in animals of the synchronous experiment, and 
this can most probably be attributed to the effect of stress related to 
manipulations with these animals. 


5] 











., the experiment aboard Cosmos-1129 yielded data that confirmed the re- 
sults of prior studies aboard Cosmos-782 [5] and Cosmos-936 [6, 7] biosatel- 
lites. The new finding was increase in SD activity, which had not been ob- 
served before, as well as decrease in FDP and G6P activity in flight animals. 
For the time being it is impossible to interpret this decrease in FDP and GO6P 
ictivity. Judging from the liver glycogen concentration (lowest in the 
vivarium control), the cause of such decrease in FDP and G6P activity could 
be the activating influence of the acutely reduced feedintake by vivarium 


control rats. 


However, the studies revealed [16] that feed intake was about the same by 
inimals in the flight and control groups. 


(he inerease in AST and ALT activity is apparently reiated to activation 
of gluconeogenesis. Although activity of FDP and G6P, which are the key en- 
zymes of gluconeogenesis, was not elevated, on the contrary, it was diminished, 
the significant increase in glycogen content of the liver in flight rats was 
indicative of increased gluconeogenesis. In all likelihood, such a high con- 
entration of glycogenwas the cause of increase in weight of the Liver and 

low concentration of protein in the flight group of animals. 

quality and quantity of feed taken in may also affect activity of 

liver enzymes (in addition to high concentration of glucocorticoids I! 
tarving increases AST, ALT [17] and G6P [18] activity. We can rule out 
qualitative differences in feed taken by different groups of animals in our 
‘riment. The quantity of feed taken by flight and control animals was 
about the same, both during the spaceflight and in the recovery period; how- 


r, the percentile level of nutrients in feces was high in tlight rats 
(a mpared to control animals) [16]. Such an increase in percentile 
level of nutrients in feces, with the same food allowance, is indicative of 
ther a change in metabolic processes or poorer assimilation of nutrients 


n the gastrointestinal tract. 


Thus, the weight loss that we demonstrated in the flight group of rats wa 
elated to decreased feed intake. The results of the studies indicat 

inge in feed intake could not be the cause of the demonstrated 

in activity of tested enzymes of the liver. Apparently, these 


Inge an be attributed solely to the influence of elevated level of gluco- 
rticoids released due to stress. The obtained data are entirely consisten 
results of assaying corticosterone concentration of blood plasma in 


this experiment [19]. 


influence of repeated immobilization stress in the recovery period wa: 
ted by increase in activity of only briefly activated enzymes, TAT 
j 


Y ind decrease in glycogen content, and thes: hanges were noted li! 


‘ht rats, as well as animals of both control groups. 


findings warrant the conclusion that, after a spaceflight, rats 
re bject to acute stress, apparently related to landing ot the bio- 


itellite 








4, 


es | 
. 


LO. 


13. 


14, 


17. 


LS. 


BIBLIOGRAPHY 
Nemeth, S., Vigas, M. et al., ENDOKRINOLOGIE, Vol 69, 1977, pp 87-89. 


Hanninen, 0. and Hartiala, K., ACTA ENDOCR. (Copenhagen), Vol 54, 196/7, 


Nistico, G. P. and Preziosi, P., PHARMACOL. RES. COMMUN., Vol 1, 1969, 
pp 363-365. 


Nemeth, S. and Vigas, M., ENDOCR. EXP., Vol 9, 1975, pp 100-105. 
Macho, L., Nemeth, S. et al., KOSMICHESKAYA BIOL., No 3, 1980, pp 26-29. 
Nemeth, S. and Tigranyan, R. A., Ibid, No 1, 1982, pp 77-80. 


Nemeth, S., Macho, L, et al., ADVANC. SPACE RES. COSPAR, Vol 1, 1981, 
pp 7219-224. 


Harper, A. E. and Bergmayer, M. W., in "Methods of Chemical Analysis,” 
Weinhelm, 1962, pp 788-794, 


Diamondstone, T. J., ANALYT. BIOCHEM., Vol 16, 1966, pp 395-401. 


Knox, W. E. and Auerbach, V. H., J. BIOL. CHEM., Vol 214, 1955, pp 307- 
313. 


Taketa, K. and Pogell, B. M., Ibid, Vol 240, 1965, pp 651-662. 
Goldstein, L., Knox, W. E. et al., Ibid, Vol 237, 1962, pp 2855-2860. 


Bergmeyer, H. U. and Bernt, E., in "Methods of Enzyme Analysis," 
Weinheim, Vol 1, 1974, pp 769-773. 


Korec, K., "Experimental Diabetes Mellitus in the Rat," Bratislava, 
1967, pp 16-17. 


Lowry, O. H., Rosebrough, N. J., Farr, A. L. et al., J. BIOL. CHEM., 
Vol 193, 1951, pp 265-275. 


Kondrat'yev, Yu. I., Danilova, A. K. et al., in "Kosmicheskaya biologiya 
{i aviakosmicheskaya meditsina" [Space Biology and Aerospace Medicine], 
Moscow-Kaluga, Pt 2, 1982, pp 135-136. 


Rosen, F., Roberts, N. R. and Nichol, C. A., J. BIOL. CHEM., Vol 234, 
1959, pp 476-479. 


Weber, G., Singhal, K. L. and Stamm, N. B., SCIENCE, Vol 142, 1963, 
pp 390-396. 


Kvetnansky, R. and Tigranyan, R.A., KOSMICHESKAYA BIOL., No 4, 1982, 
pp 89-90. 


53 











UDC: 612.646.014.477-019:; 597 
ROLE OF GRAVITY IN EARLY EMBRYOGENESIS OF THE TELEOST, BRACHIDANIO RERIO 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 33 (manuscript received 10 Aug 82), pp 37-40 


[Article by Ye. M. Cherdantseva] 


[English abstract from source] The effect of turning and 
clinostating exposures on the early embryogenesis of the teleost 
B. rerio was investigated. The eggs turned immediately after 
fertilization with their animal pole downwards and kept so till 
the formation of the axial complex developed in an absolutely 
normal way. Most eggs also developed normally during clinostat- 
ing, when kept in the inclined and horizontal clinostats. During 
this exposure eggs of some clutches perished. They were those 
eggs which were unable to develop near the lower limits of the 
temperature range characteristic of B. rerio development 
(18-19.5°C). 


[Text] Direct involvement of environmental factors in primary egg polariza- 
tion (i.e., establishment of its polarity and bilateral organization) is 
unlikely, if only by virtue of variability of such factors. Gravity is the 
only exception, and the question of its involvement in early morphogenesis 
of animals definitely requires further investigation [{1l, 2]. 


Among the lower vertebrates, the role of gravity in egg polarization was 
studied almost exclusively on the example of amphibians, which are animals 
with holoblastic type of development. In holoblastic development, the 
animal-vegetal polarity (AVP) of the ovum is manifested, in particular, by 
nonuniform distribution of cytoplasm constituents differing in specific 
gravity, whereas dorsoventral polarity (DVP) is related to asymmetrical 
distribution of internal components of cytoplasm (primarily the heavy 
large-grain yolk) in relation to the animal-vegetal axis (AVA). Since the 
egg turns after fertilization with the animal pole up and maintains this 
orientation to the start of gastrulation, apparently gravity could be 
instrumental in stabilization of AVP starting at the time of fertilization, 
maintaining the initial nonuniformity of distribution of heavy and light 
elements of the egg. 


fhe results of numerous experiments conducted to investigate the turns and 
moderate centrifuging of amphibian eggs [3, 4] indicate that altered 


54 


gravity elicits inversion of both AVP and DVP, At the same time, the 
results of inflight experiments [5] and clinostat experiments on developing 
roe indicate that egg polarization occurs normally or almost normally in both 
weightlessness and conditions simulating some of the effects of weichtless- 
ness [6]. 


Evidently, this is attributable to the fact that there are several] different 
mechanisms, which replace one another when ambient conditions change, that 
are potentially involved in polarization of the ovum. Gravity in itself may 
not necessarily be a factor in egg polarization, but a change in its effects 
could influence the choice of polarization mechanism. Thus, according to 
data in [4], the mechanism of DVP of the amphibian ovum is different with 
altered gravity than in the usual course of development. 


In virtually all of the experiments that demonstrated the effect of altered 
gravity on early morphogenesis in holoblastic development it was noted 

that the effect of gravity is manifested by redistribution of heavy and light 
constituents of egg cytoplasm in accordance with their new equilibriun. 
However, the mechanism of effects of gravity in the case of meroblastic develop- 
ment has been virtually unstudied. The fact of the matter is that, with the 
meroblastic type of development, AVP is not related to nonuniformity of dis- 
tribution, but to virtually complete reciprocal segregation of the heavy 

yolk and light, yolk-free cytoplasm. Since, in meroblastic development, the 
yolk and cytoplasm constitute phases that are separated from one another 

but endogenously homogeneous, the influence of gravity on early embryogenesis 
should be different than in animals with holoblastic type of development. 


The results of experiments involving testing of the effects of weightlessness 
and clinostatic position on embryogenesis of teleost fish, which are the only 
representatives of meroblastic development among lower vertebrates, have 
several substantial flaws for an embryologist. For example, in experiments 
involving exposure of Fundulus heteroclitus roe to clinostatic factors, 
precooled roe was used, and this could have had an appreciable effect on the 
result of the experiment [7]. The flight experiments with Fundulus [7] 

were begun at too late a stage of its development. In any case, the results 
of these experiments indicate that development of teleost fish embryos in 
weightlessness occurred more or less normally. 


For this reason, it can be assumed that gravity, if it does affect fish 
embryogenesis, has a rather minimal effect. Expressly this circumstance 
stresses the need to continue with ground-based experiments. If it is found 
that this factor has a mild effect on embryogenesis, it would be manifested 
more on the population level than the individual morphological level, 

and there would be regulation of early developmental disturbances. This 

is indicative of the need, in the first place, of taking into consideration 
the influence of gravity on a population and, in the second place, to con- 
tinuously monitor the course of development, and for the time being this 

is feasible only under laboratory conditions. We submit here the results 
of experiments conducted to investigate turning and clinostating of 
developing roe of the teleost fish, Brachidanio rerio. 








Methods 


In our study we used the roe of the aquarium fish, B. rerio. Lach spawn of 
row was obtained after crossing one female with 3-6 males. After tertiliza- 
tion, all of the yolk-free cytoplasm collected on the animal pole of the 
ovum, forming a blastodisk. The AVA does not have a strict orientation in 
relation to the vertical plane either during formation of the blastodisk or 
subsequent developmental stages. It could be vertical (with the animal pole 
up), at different angles away from the vertical plane, perpendicular to the 
vertical; finally, some roe could be slightly inclined with the animal pole 
down. The yolk is separated entirely from the blastodisk cytoplasm and forms 
the yolk sac, which is covered by a thin layer of cytoplasm. Only blasto- 
disk material is involved in cleavage, and syncytium is formed on the boundary 
between the yolk sac and blastoderm from blastomeres that are in contact 

with the yolk sac; the synevtium plays an important part in both transport of 
nutrients from the yolk to blastoderm and basic morphogenetic movements. 


In the experiments conducted to study turning, roe in yolk sacs was placed in 
plexiglas wells, turned with the animal pole down and lightly pressed 

against the inner side of the sac using preparation needles. The roe 

idhered to the sac, and this is what kept them in overturned position. 

We checked the orientation of the roe every 30 min using a binocular. In 
all, we examined 100 individual ova developing all of the t.me in inverted 
position, starting with formation of the first cleavage groove to formation 
of the axial complex. 


in expriments with clinostating, the roe was packed tight in gauze bags 

that were secured in chambers with semipermeable polyethylene walls filled 
with settled water. The chambers were on the drum of a horizontal clino- 
stat, which rotated about the horizontal axis at the rate of 30 r/min. By 
Jirtue of the tight packing, the roe together with membranes did not shift 
within the chambers. As for rotation of roe within the sacs, it can be noted 
that, when inverted, they rapidly (within 2-3 s) turned to a very small angle, 
lropped to the bottom of the sac, adhered to it, after which they rotated 

very slowly. The roe either failed to return to its initial orientation in 
relation to the vertical plane or did so very slowly (within 7-10 min). 

fhus, the roe returned to its initial orientation considerably more slowly 
after turning in the gravity field than the rate of rotation of the clinostat. 


Experiments were conducted in the following manner. From each spawn we took 
150 ova, placing 50 of them on a horizontal clinostat (HC), 50 on a tilted 
clinostat (TC) rotating at the same rate as the HC but about an axis at an 
angle of 45° in relation to the vertical plane. TC and HC conditions were 

the sane but, in the TC, unlike the HC, there was a constant gravity component 
if Ge¥2, which was active along the axis of rotation. 


Finally, 50 eggsthat served as the main control (C) were left to develop in 
stationary chambers. All three batches of roe from each spawn (TC, HC and C) 
developed at a temperature of 23-24°C. 





Results and Discussion 


Roe turned with the animal pole down developed normally in all cases, synchro- 
nously with development of control roe (developing in the same plexiglas 

wells, but with the animal pole up). The only roe components that could have 
moved with change in effect of gravity were the vitelline membranes, which fill 
the yolk sac (in B. rerio, the yolk is granular, rather than liquid as in 

many teleosts). However, histological analysis revealed that the distribution 
of yolk membranes does not change when the eggs turn around. There is a 

layer of fine vitelline granules right under the vitelline syncytium, while the 
large yolk membranes occupy the remaining part of the yolk sac. As we know, 

in teleosts there is active transport of yolk from the yolk sac to the blasto- 
derm through the yolk syncytium, so that the granules under the layer of 
vitelline syncytium are constantly broken down into smaller elements. Since 
there is no change in either rate of development or distribution of yolk mem- 
branes aS a result of overturning of eggs, the change in orientation of the 

egy in the gravity field does not affect yolk transport. 


Table 1. Effect of clinostatic factors on early embryogenesis of 8. rerio 











awn | lino- | Survival of | Surviva »f 

ta of development] No tating ehenoste, % 1 control. 4. 

| time, HC | TC | 23°C | 19% 

- a _— = — ———e . nz | _ —-— —— 
9 leavaae _— ls & 24 | 0 | 0 |95~—100! 1.-2 
(0-64 blastomeres) 2 | 7 0 | 0 | 95-100} i—2 
3 7 | 5 | 1 | 100 | 1-2 
23 | 100 | 100 | 100 12 

7 0 10 | 99—109 l 

5—11 | 5—8 &24~28| 100 | 100 | 100 100 

ite cleavage (64- 12 7 0 | o | 300 12 
Ee hinetmmmina 26 35 | 100 | 100 1—2 
250 LasSsto res) 13 o4 48 100 | 100 | 2 
14—22 | 5—8 6 24—28| 100 | 100 6} «100 100 

' 























Table 1 lists the results of experiments conducted to test the effects of 
clinostatic factors. As can be seen in this table, most sets of roe were 

not sensitive to clinostatic factors, in spite of the fact that the clinostat- 
ing process was mostly begunvery early, immediately after formation of the 
blastodisk. At the same time, in six sets of roe development of a consider- 
able part of the embryos was drastically impaired in clinostatic position, 
with reduction of survival rate. It should be stressed that there was mass 
scale embryo death in both HC and TC, whereas only isolated instances of 
embryo death were observed in the main control. The roe of all clinostat- 
sensitive sets was incapable of developing at a temperature of 18°C. This 
temperature is the bottom of the range of temperatures for development of 

B. rerio, and embryos of resistant sets of roe develop normally under these 
conditions. It should be stressed that sensitive roe was also more demanding 
with regard to other ambient factors, for example, aeration, but under optimum 
conditions their development did not differ in any way from that of embryos 
from resistant sets of roe. Thus, sensitivity to clinostatic factors is 








manifested only in the few spawns whose development was destabilized from the 
very beginning (i.e., regardless of the factor proper). Death of embryos 
referable to sensitive sets of roe in HC, TC and at low temperature occurred 
before gastrulation and was related to the same syndrome, which included 
partial suppression of cytotomy [cleavage?] with continuing divisions of nuc- 
lei, as well as proliferation of vitelline syncytium, which pushes blastoderm 
from the surface of the embryo. Table 2 lists results of taking measurements 
on histological sections with regard to volume of yolk syncytium and blasto- 
derm in embryos from sensitive spawns in HC and TC, as well as control embryos 
from sensitive and resistant sets of roe. As we see, there is more marked 
impairment of proportions of syncytium and cell blastoderm in HC than TC. It 
is remarkable, that these proportions were also impaired in the C, among 
embryos from sensitive roe, as compared to embryos of resistant sets of roe, 
which stresses once more the presence of initial differences in development 
of both types of roe. 


Table 2. Relative volume of periblast (yolk syncytium) 





























Sensitive spawn embryos ee | Resistant spawn 
spawn 2 Spawn 12 embryos (control) 

——— — ea : 
HC =< | C HC | TC | C spawn 7, spawn 15 
76 15 7 18 20 | 8 4 5 

46 26 8 20 18 | 6 5 4 

33 | 31 10 29 14 i) 5 5 

8] 18 9 16 13 | 10 6 6 

62 32 22 14 

| | 

















Note: We sketched in complete series of paraffin sections of each embryo on 
paper of uniform density. The relative periblast volume was calculated 
as the ratio of overall periblast area on all sections to overall area 
of blastoderm and periblast on all sections. On the pattern of each 
section, the area of periblast and blastoderm was determined from the 
weight of the corresponding sections of the paper (weighed with 
accuracy to the nearest 0.1 mg). 


The differences between HC and TC in spawn 2 are statistically signi- 
ficant at p<0.01 according to Wilcoxson's U criterion. The differ- 
ences between HC and TC in spawn 12, as well as differences between 
Csens [sensitive] and C,,, [resistant] spawns are statistically 
reliable with p<0.05 according to Wilcoxson’s U criterion. 


The inability to develop among embryos of sensitive spawns near the bottom 

of the temperature range is indicative of depressed metabolism. There was a 
marked tendency in control embryos of sensitive spawns toward reduction of 
area of the boundary surface between interacting parts of the embryo--blasto- 
derm, syncytium and yolk sac. [It can be assumed that embryos from sensitive 
spawns have lower overall activity of contractile structures, which are re- 
presented in teleosts by numerous microfilaments of different types [8]. 
Interestingly, this tendency is accentuated in HC, as compared to TC. 


IO 








Thus, the clinostat effect is manifested only when overall stability of 
development of a given spawn is markedly diminished and, consequently, the 
range of ambient conditions that provide for normal development of teleost 
fish is narrower. 


To what can the differences in stability of early morphogenesis be related? 
The simplest assumption is that the decrease in resistance of roe to exogenous 
factors is related to the physiological state of the females during spawning 
(for example, the females produce immature or overmature roe). However, we 
cannot rule out the possibility that the decline of this parameter is 
attributable to distinctions in the female genotype. We obtained half of 

the sensitive spawns from the offsnring of the same female, i.e., half the 
sensitive embryos were half-sibs. 


BIBLIOGRAPHY 
l. Pollard, E. C., J. THEORET. BIOL., Vol 8, 1965, pp 113-123. 


2. Dorfman, Ya. G. and Cherdantsev, V. G., in "Vneshnyaya sreda i 
razvivayushchiysya organizm" [The Environment and the Developing 
Organism], Moscow, 1977, pp 140-173. 


tl 


3. Schleip, W., "Determination of Primitive Development," Leipzig, 1929. 


Kirschner, M. W., Butner, K. A., Newport, J. W. et al., NETHERLAND J. 
ZOOL., Yol 31, 1981, pp 50-77. 


;/ 


5. Young, R. S. and Tremor, J. W., BIOSCIENCE, Vol 18, 1968, pp 609-615. 


6. Nace, G. W. and Tremor, J. W., PHYSIOLOGIST, Vol 24, No 6, 1981, 


Belousov, L. V., Dorfman, Ya. G., Ignat'yeva, Ye. L. et al., in 
"Biologicheskiye issledovaniya na biosputnikakh 'Kosmos'" [Biological 
Research Aboard Cosmos Biosatellites], Moscow, 1979, pp 62-69. 


~ 


8. Betchaku, T. and Trinkaus, J. P., J. EXP. ZOOL., Vol 206, 1978, 
pp 381-407. 








UDC: 612.646.014.47:531.351J-019:597 


EFFECT OF CENTRIFUGING ON EARLY EMBRYOGENESIS OF THE TELEOST, BRACHIDANIO 
RERIO 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 10 Aug 82) pp 41-45 


[Article by Ye. M. Cherdantseva] 


[English abstract from source] The early embryogenesis of the 
teleost Brachidanio rerio has been shown to be resistant to 
centrifugation. Beginning with the blastula stage, the develop- 
ment proceeds normally in 90% embryos centrifuged at 500 g for 
lh. Beginning with early developmental stages, embryos grow and 
develop normally when exposed to long-term centrifugation at 

50 g. The exposure produces partial inhibition of cytotomy (with 
nuclear division continued). This effect changes the proportions 
of the cellular and syncytial fractions of the embryo (blasto- 
derm and periblast). The exposure to centrifugation also reveals 
the dorsoventral asymmetry of egg surface tension. Resistance to 
centrifugation is attributed to the fact that the polarization 
control is beyond the cell embryonic fraction. 





[Text] The results of studying the effects of clinostatic and overturning 
of teleost eggs [1], as well as of the few experiments involving centrifuga- 
tion of roe, are indicative of high resistance of early embryogenesis in 
vertebrates to altered gravity. Thus, overturning of developing roe of 
Brachidanio rerio does not affect either distribution of the main internal 
constituents of the egg or transport of substances from the yolk sac to 
blastoderm, and there is normal development of overturned embryos. Such 
resistance to altered gravity is not quite inherent in lower vertebrates 
with their yolk-rich eggs. It is remarkable that expressly the embryos of 
teleost fish, which are the only representatives of lower vertebrates with 
meroblast type of development, are resistant. Evidently, the resistance to 
altered gravity must be due to some distinctions of mechanisms of primary 
polarization of the egg in the case of meroblast type of development. 


t 
r 
f 


These mechanisms have been virtually unstudied in fish. Centrifuging eggs, 
which is one of the classical methods of studying polarization mechanisms, 
did not yield clearcut results heretofore [2]. We submit here the results 
of experiments involving centrifuging of developing eggs of the teleost, 


60 








B. rerio. We devoted special attention to mechanisms of formation of dorso- 
ventral polarity of the embryo, since analysis of these mechanisms enables us 
to comprehend the causes of resistance of early embryogenesis of fish to the 
effects of altered gravity. In our study, we used rather high levels of 
accelerations (on the order of 500 and 50 G), since it is known that lower 
accelerations do not affect the course of early development. 


Methods 


A brief description of early embryogenesis in 8. rerio was provided in our 
previous work. For analysis of the material we used the tables of normal 
develorment of B. rerio [4]. The eggs of B. rerio were centrifuged at succes- 
sive stages of development, starting with formation of the blastodisk (stages 
II and III in the tables of normal development) and ending with termination 

of epiboly (stages XIX-XX). Eggs in vitelline membranes were centrifuged 
without prior orientation at accelerations of 500 and 50 G. At each of the 
studied stages of development, the embryos were centrifuged for 15, 30, 60 

and 120 min at 500 G and for 4, 5, 7 h at 50 G. After centrifuging, the 
embryos were placed in plexiglas wells, oriented and we observed the course 

of their subsequent development in order to determine the continuity between 
distribution of the main constituents of embryonic material and arrangement 
of the main morphological axes of the egg. We used the usual methods of 
preparation and staining of serial paraffin sections for histological analysis. 


Results and Discussion 


Centrifuging at 500 G. Figure | illustrates the results of centrifuging 
B. rerio eggs. As can be seen on the histograms, there is constant increase 
in resistance of embryos to centrifuging in the course of development. We 
were able to distinguish four periods of development, which differed both 

in mechanism of effect of centrifuging on morphogenesis and resistance of 
embrvos to this effect. 


Early cleavage (stages I-VII). In the case of normal development, 
this period corresponds to the stages preceding formation of vitelline syn- 
cytium (periblast), which is formed from blastomeres next to the yolk sac. 
The effect of centrifuging is manifested primarily by suppression of cytotomy 
and straightening out of the already formed cleavage grooves; but nuclear 
division continues. There may be complete or partial depression of cytotomy; 
in the former case, all of the blastodisk material acquires the structure of 
syncytium and in the latter, part of it does so. For expressly this reason, 
l-h centrifugation, which depresses cytotomy completely, leads to complete 
death of embryos. After centrifuging for 30 min, some embryos do survive; but 
with centrifuging for 15 min a considerable part of the embryos survives. In 
all cases where postcentrifuging development was regulated, the ratio of 
syncytial volume to cell fraction volume was close to normal. Among other 
sequelae of centrifuging effects on early cleavage, we should mention the 
appreciable increase in mutual segregation of material of the blastodisk and 
yolk sac. The fact of the matter is that part of the cytoplasm covering the 
yolk sac flows into the blastodisk cytoplasm, so that there is sharper 
delineation of the blastodisk boundaries than in normal development. 


61 
































- 
r 
! 113 
in =m 
0) 
34 244 142 
hw 
90 60 120 
15) mt 
c 
‘= 
60 120 
7 a: 
178 158 
d 
al we 68 
60 120 
Figure l. 


Effect of centrifuging on early 
embryogenesis in Brachidanio rerio 
(500 G). The numbers above the 
histograms refer to number of eggs 
analyzed and those under the histo- 
grams, to duration of centrifuging 
(in min). Black bars represent 
anomalous development, stripped-- 
death and white--normal development 
(Z) 

2) early cleavage 

b) late cleavage 

c) blastulation 

d) gastrulation 


[In addition, we should mention that 





populations of 
served in some places in embryos with formed complexes. 
an "“embryonic" appearance and never participated in forming embryonic tissues. 


Blastulation (stages XII-XIV). 
formed in normal embryos and centrifuging leads only to redistribution of its 
material: the central part of the periblast is markedly thinned down, 

whereas the marginal part, situated on the surface of the embryo under the 
bottom boundary of the blastoderm is, on the contrary, 


Late cleavage (stages X-XI1). In 
the case of normal developed, vitelline 
syncytium (periblast) is formed in this 
period, which is situated on the boundary 
between the blastoderm and yolk sac. As 
in the preceding period, centrifuging 
depresses cytotomy of superfixial blasto- 
meres, but cytotomy of internal blasto- 
meres continues, though much more slowly. 
Slowing of cytotomy of internal blasto- 
meres is manifested by a profusion of 
metaphase plates and spindles, which are 
observed immediately after centrifuging. 
As a result of slower cytotomy, there 

is impairment of proportions of periblast 
and blastoderm (ratio of syncytial volume 
to cell fraction volume increases), but 
to a lesser extent than in the course of 
early cleavage, and this is what leads 

to appreciable decline of embryo deaths. 
Moreover, the blastoderm acquires a 
mosaic-like structure and consists of 
cells that take up stain differently in 
histological preparations: "dark" cells 
with strongly stained cytoplasm differ 
drastically from the "light" ones, whose 
cytoplasm remains virtually unstained. 

In the case of centrifugation during 

late cleavage, the embryos develop a 
considerable number of diverse structural 
abnormalities in the axial complex. It 
becomes shorter and crooked, and some 

of its parts (cephalic, caudal or trunk 
structures) are underdeveloped. Al- 
though we did not obtain embryos with a 
double set of axial structures in any 

of the experiments, local duplication 

In the region of the hind brain, trunk 

or tail) were encountered quite often. 
"clear" cells were pre- 
These cells retained 


By this time, the periblast is completely 


thickened. The struc- 


tural abnormalities of the axial complex that occur in centrifuged embryos 
are similar in nature to those observed when centrifuging was effected during 
late cleavage, but there were much fewer embryo deaths. 









































Figure 2. Figure 3. 


DVA of eppe centrifuged (500 G) during DVA of periblast after centrifuging 
early cleavage (i.e., before formation (500 G) 


of periblast) 


Here and in Figure 3: In Figures 2 and 3 staining with a mixture 
ll) periblast of Ponceau rose and solid green, magnifica- 
BJl) blastoderm tion 1010, 


KM) yolk sac 


Gastrulation (stages XI-XX). Starting with gastrulation and to the 
end of formation of the axis complex, centrifugation has virtually no effect 
on the course of development, not counting some slowing of epiboly, which is 
readily regulated and does not leave any abnormalities. 


Centrifuging at 50 G. Starting with late cleavage (i.e., start of 


periblast formation) one can centrifuge B. rerio embryos at 50 C continuously 


to the start or eve end of gastrulation (i.e., for 4-/ h). There is com- 
plete regulatio t development of such embryos. Prolonged centrifuging at 
50 G elicits the same type of changes as short-term centrifuging at 500 G; 


however, these changes are milder at 50 G, and for this reason easier to 
regulate. 

Centrifuging and dorsoventral asymmetry (DVA). Centrifuging always 
elicited noticeable deformation of eggs, and from its nature one could deter- 
mine their orientation during centrifugation. In some cases, egg deformation 
was clearly asymmetrical, i.e., centrifugal force acted at an angle to 

the animal-vegetal axis (AVA) of the egg. But in the vast majority of cases 


+ A 


the eggs were detormed along the AVA. 





-_- 


ntriluginwg consistencti 1 { rast 
ial emb) } pe ert (rig ‘ ) dy). 
eavage (betore the start of peribia forna- 
by the llowing signs: regi itter- 
lastodisk was always taller or ie edge 
i ir re ed much more nt tnin 
k one; the tine yolk granules atta ed ti 
mittee to its thir edge. When embryo 


e thin edge of the blastodisk, whereas the 


‘ } : 
side the embryo) usually tormed 


= start I pert} | ist formation (1.,@., 


nd blastulation), asymmetry is manifested 


mat one oO! lt edges, wonereas Trorming 
ites if t his D] ) ite « ive, ne eget 

] ] ! } ~} ‘ 
nas to t aorsaj »>1LUet oO! tne . IDTYO, 


a | | is 
‘ ’ j . 
~ , ? as ° rrr «os 
Li > i@ia Se , 4 i 4s ( pr Ol 
" , ‘ 
, ) +» crilor ’ ‘ ‘ ynrvo ( j f 
ad i ‘ i bdis a . *% 
¥ - ¥ ,; * y 4 1] , ne > + , r) 
; s i> LT} P| sa l i ¢ i 


mw, » ‘ ei £ 
, , 7 , 
LOT) | t . I ir pe ( Le i riruginy. 
, ¢ _* " 
s ( i ' t i ( ldlllio i actlio 
’ ry’ cy? ; ] ] r r ‘ ( ¢ Cy? 
ie ; t i ial . ii i is | 
+ ; ‘ ; ‘ ; > on 
LDi ‘ Daift te! ribpias 
) ] ] ‘ ; 
esult irti epre on of cyto- 
’ 7 14 j ] ‘ 
‘ o* } 4 
r | I i } il i ? ‘ siViGG A u' 
; irr ey } ‘ ri Orit t 
’ ‘ 7 > , 
" , " 
[ 4 i ° i j { f iT 
P ’ 
Y y 
» * ,. > JU) i 
a 7 
’ _ ’ ‘ j 
? ( r 
i 
, , y 
¥ rd i 
, , , 
reid ’ P' y 
7 . > 
) 
i 
y , ‘ , ] i 9 
y » * ‘ 
i ‘ - > | 
, ’ , ¢ ‘ 
. 
> > 
P 
- ‘ ‘ 
é j lire 
‘ 





was not known until now. According to our data, the periblast is this sub- 
trate, There are a number of signs indicating that there is greater pert- 
blast tension on the future dorsal side of the embryo than on the ventral 
side, This explains the common DVP of the blastoderm, This is indicated 
primarily by the displacement of the periblast to the dorsal side during 
centrifuging, the lesser tenston of blastoderm on the dorsal side than on 
the ventral side and, consequently, considerably less depression of cytotomy 
(it is known that the degree of depression of cytotomy is directly related 
to the degree of tension of the cell surface). All this renders plausible 
the hypothesis, according to which DVP of teleost embryos is determined by 
the periblast tension gradient. 


Thus, control of blastoderm polarization is maintained regardless of redistri- 
bution of components of its material. Such control of polari-ation is 
apparently the consequence of meroblast type of development, and it is a 

good explanation for the resistance of meroblastic development to the altered 
effect of gravity. In particular, this is corroborated by the fact that, in 
B. rerio, resistance to change in effect of gravity increases with particular 
intensity after cessation in normal development of exchange of material 


between the blastoderm and periblast. 
BI BLLOGRAPHY 
| ¥ ’ ‘ y , ' 4 
l. Belousov, L. V., Dorfman, Ya. G., Ignat’yeva, Ye. L. et al., in 
_ , . 2 ; , tu et . and 

"Bilologicheskiye issledovaniya na biosputnikakh ‘Kosmos [Biological 
Studies Aboard Cosmos Biosatellites], Moscow, 1979, pp 62-69. 

2. Shaver, J. R., BIOL. BULL., Vol 101, 1951, p 201. 

s, Tung, T. C., Wu, S. C. and Tung, Y. F. Y., ACTA BIOL. EXP. SINICA, Vol 4, 
1955, pp 365-383 


+. Hisaoka, K. K. and Battle, H. 1., J. MORPH., Vol 102, 1958, pp 311-328. 


5. Tung, T. C. and Tung, Y. F. Y., PROC. ZOOL. SOC. LOND., Vol 114, 1944, 








UDC: 616-001.12-084]-07:616.24-008, 4-02:546.1/7 


INFLUENCE OF ADDITION OF NITROGEN TO INHALED OXYGEN ON EFFICACY OF TWO-HOUR 
DENT TROGENATION BEFORE DECOMPRESSION FROM 760 TO 220 MM HG 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol l1/, 
No 4, Jul-Aug 83 (manuscript received 25 Jun 82) pp 45-47 


[Article by A. S. Barer, M. I. Vakar, G. F. Vorob'yev, L. R. Iseyev, 
S. N,. Filipenkov and V. I. Chadov] 


[English abstract from source] The ground-based experimental] 
study of denitrogenation by oxygen breathing showed that two- 
hour denitrogenation was inadequate if the breathing gas con- 
tained about 10% nitrogen or if the process included 3-10 min 
of air breathing. The reduction of the nitrogen content in the 
breathing gas to 0.4-5% eliminated severe forms of the 
decompression disease and decreased significantly the incidence 
of its mild forms to 3.2%. This allowed work cf moderate load 
£ 


at the ambient pressure 220 mm Hg ; fter two-hour breathing of 
oxygen with nitrogen admixture of no more than 5/, 


[Text] Denitrogenation when breathing with oxygen is the most popular 
1 of preventing altitude decompression [caisson| disease (ADD) when the 

itmosphere is highly rarefied. However, in practice this could be associated 
with admixture of air and, consequently, nitrogen in inhaled oxygen. The most 
probable cause of this is incomplete sealin oxygen breathing apparatus (OBA) 
ind particularly of oxygen masks (OM). To date, complete enough quantitative 
lata have not been published about the significance and levels of added 
nitrogen in inhaled oxygen during rebreathing and its role in subsequent 
nset of ADD. It is only known that, in this case, there is a decline in 

te of denitrogenation [1, 2] and, consequently, a greater probabili 





jective here was to test 2h prebreathing with use of oxygen mask 
the ground, with delivery of oxygen from an instrument operating lik 
i jung machine. Analysis of experimental material and its separation into 
es was made on the basis of amount of nitrogen in the space under th 
mask. The efficacy of prebreathing with different levels of nitrogen in 


the inhaled gas, as well as with brief inhalation of air upon conclusi 
2-h oxygen breathing was assessed from the incidence of ADD after decompressi 
to an absolute pressure of 220 mm Hg and performance of moderate exerci 


the subjects. 


66 











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] > ‘ ; “at 
CY i i " i .f { ’ eS i it itt ) 
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ri re . l Hg 2 reatnlns Jil Ai 
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, ‘ , , , 
; } ; , " , ; ; wf ‘ 
{ 7 I r) ex VOI 1 tney exerci] } ifn) ] Ordcail 
, + . r . P “rr _ 4 ’ 
; el : j O tests, prio t iecompresslun 
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| eee | . ni | 3.3 and 32.12, respectively, of the 
aeaiiesien : : "i | { { , We failed to demonstrate 
rie | tati ically significant differences 
~ | SWAS , | | yetween the results in these two series. 
iSNO| < = cal sa} ‘\ rease in nitrogen concentration 
: in inhaled gas to 0.4-5.0% as a result 
tt a better individual fitting of the 





an a | 
as - L Aan aca . . . p< c 
% asks and additional checking of the 
¥ MI YNY 
- ~ lheeetana ! . leew S watds } 
* ’ Ld ; Ated AR ii tne test > reduc eda reliabl y 
“, = . “ . . = , / ; 
< i} 1 t - 7 AT)T) 
927 (P<0.001) the incidence of ADD (3.2 
4; Samo" ie third series of tests). ne tnen 
— 
' 
« ae » & } no . ary? 
: bse ! only mild forms of ADD, 
=4 i> f 
* 4 ‘ — T - : / } ae rr 
: trades I-II, and the entire 4=<h program 
J ; ; 
t . ae a nrY ca roa ~* 997) Ho 
> Jt exercise at pressure OF 2£2VU Im Ng 
¥ HO tHd aa _ - , ° .¢ _ 
- a . ? . ¢ } 
r - rformed in all 93 tests. Thus, 
>y - - ~ 1 ‘* se ia J . . . i . 
3 : 440 - thi licated denitrogenation condi- 
INOHS  s : 
| = tion ith 2<h oxygen breathing, when 
6 i ; 4 Xi il VV) Sh i i) wt Se F | 9 i i 
<, NIXS! . _ | tcnere Wa up CO Dh nitrogen present 9 
’ . 
os - - . | W ‘ >] it 1 ' Cl , ire. 
- ' 
7 of the effect ba 
- ¥ a " i Wa : 4 ~ 
- . - ) = ries | | r on efficacy of 2-h pre- 
+ ~ , * 2 
- ° ~ ) { , t ide Ln iif ast , <7 ee 
a . , 
2 n 7 P - > wn ac J id j oy maw 
- ' - . 
rit LOr 1 ni iiat Lon ‘en! 117% 
- ,LNOHY 4 Z )™ - mnitrogen ore ItTNiINng, 
. NBAID - ; ' 
. 545234 o; <= : > | t io more tnan o4 nitrogen content 
: HAGAN ; > . : j 
w2svD> aa i re. - 1D je" CS wWwnhoO 44 not 
¢ r ith Z=-nh prebreatnin in 
| 52 a : nd III tests participated 
, ~ 7 + naw om [ 4 l = ° iS¢t [ 4 ne, 
. * ’ } T l > Set r f ut »? one’ 
‘ Were >I it ] 3 ] i] Ll: 
Ai j r 4 },UD) evid ice oO! | C= 
4 7 > ' A . 1 : 
rt ? ( ‘ , aS ompared ) ne ] 
JO 4 ; ries. The incidence of 
= 3 \ , . i | 11; sita LT 
; t Liak JUL « ) SA @ 
— = : os a 2 f ration orf air 
ficvAtdasS > 





lead to consistent increase in incidence of ADD, yet ADD was noted expressly 
in 4 out of the 16 tests with J-min air breathing and in 4 out of 48 tests 
with lO=-min of air breathing. [t should be noted that, in most cases of ADD 
in this series of tests, we observed grade III symptoms, which required 
premature termination of exposure in the 45th-204th min of exposure to 
220 mm Hg. 


Thus, the results of our tests were indicative of the unsuitability of 2h 
prebreathing in the presence of 10% or more nitrogen in inhaled oxygen and 
inadmissibility of even brief interruption of denitrogenation with a period 
of air inhalation. At the same time, limiting the nitrogen content to 
0.4-5% during prebreathing virtually precluded the development of serious 
cases of ADD, reliably lowered the incidence of the disease and, in essence, 
made it possible to perform moderate work [exercise] for 4 h at a pressure 
of 220 mm Hg. 


BIBLIOGRAPHY 


l. Malkin, V. G., in "Osnovy kosmicheskoy biologii i meditsiny"” [Fundamentals 
of Space Biology and Medicine], Moscow, Vol 2, Bk 1, 1975, pp 18-34. 


», Fulton, J. E., ed., "Decompression Sickness," Philadelphia, 1951, 

pp 278-321. 

3, Allen, T. H., Maio, D. A. and Bancrott, R. W., AEROSPACE MED., Vol 42, 
1971, pp 518-524. 


4. Cooke, J. P., Ikels, K. G., Adams, J. D. et al., AVIAT. SPACE ENVIRONM. 
MED., Vol 51, 1980, pp 537-541. 


69 








UDC: 616-008.922.1-008.64-07:616.154.453 


FREE AND PROTEIN-BOUND PLASMA CORTICOSTERONE IN WHITE RATS IN THE PRESENCE 
OF HYPOXIA AND AFTER ADMINISTRATION OF ADRENOCORTICOTROPIC HORMONE 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 4 Feb 82) pp 47-50 


[Article by G. K. Abasheva and L. M. Mikhneva] 


{English abstract frem source] It has been demonstrated 
that the plasma ratio of free and protein-bound cortico- 
sterone depends on the hypoxic degree. After two-hour 
hypoxia at an altitude of 10,000 m the trained and untrained 
animals exhibit a similar content of the free hormone (217), 
with the content of total corticosterone being significantly 
lower in the trained rats. A study of variations in the 
content of free corticosterone in rats exposed to hypoxia for 
20, 45 and 120 min and ACTH administration during the same 
time intervals has shown that the binding capacity of trans- 
cortine changes 45 min after the beginning of hypoxia. 


[Text] Numerous studies have demonstrated that constitutional resistance to 
hypoxia depends on adrenal glucocorticoid function. Most authors arrived at 
the conclusion that body resistance to hypoxia diminishes after adrenalectomy 
[l-3] and increases significantly after administration of adrenocorticotropic 
hormone (ACTH) or cortisol [4]. The functional state of the adrenohypophyseal 
system had been assessed on the basis of assaying total corticosteroids of 
blood plasma and the adrenals, whereas under normal conditions 90% of the 
plasma corticosteroids are in a biologically inactive, protein-bound form [5]. 
The proportion of free and protein-bound plasma corticosteroids under hypoxic 
conditions has not been studied. We investigated these forms of the hormone 
in the course of the response of the adrenohypophyseal system to varying 
degrees of hypoxic hypoxia. 


Methods 


Experiments were conducted on male albino rats weighing 180-210 g. Hypoxic 
hypoxia was created in an aerated pressure chamber by rarefying the air 

to an "altitude" of 4000, 7000 and 10,000 m. The "ascent" lasted 10-12 min. 
We used the fluorimetric method, as modified by Yu. A. Pankov and I. Ya. 
Usvatova [6] to assay ll-hydroxycorticosteroids (11-HCS) of blood plasma. The 
transcortin-bound and free forms of the hormone were separated on columns 
containing sephadex G-50 of the Pharmacia Firm using the method of L. V. 
Pavlikhina et al. [7]. 








ae conductad9 series of experiment 
altitudes" 


TT 


hypoxia at 


le-control (intact animals); 2-4--2-h 
of 4000, 7000 and 10,000 m, respectively; 5-7--adminis- 


tration of ACTH in a dosage of 10 units/kg weight, with decapitation of animals 


20 
! 


2-h hypoxia at an "altitude' 


Results and Discussion 


As can be seen in Table 2, in the presence of h 


» 45 and 120 min, respectively, after giving ACTH; 8--acclimatization to 
hypoxia corresponding to an "altitude" 


of 7000 m for 30 days, 2 h daily; 9-- 


of 10,000 m for acclimated rats. 


xia corresponding to an 


ypc 
“altitude” of 400 m, there was virtually no change in level of free, protein-- 


bound and total plasma corticosterone 
in relative amount of its free form. 


, whereas there was a reliable increase 


Hypoxia at "altitudes" of 7000 and 


10,000 m elicited a statistically significant increase in all three forms of 


Table l. 
LI-HCS levels, in vgZ, in rat blood 
plasma during 120-min exposure to 
varying degrees of hypoxia, Mtm 











" ent ortl ;teror 
Yer. -—— a 
ALLA A , _ j _ 
Soe ME 
| | lad 
-¥ 1 17,1+1,3 2.0+0,2 | 15,4+1,2 
| (18) | (18) | (18) 
| | 
rr | oe 
4 000 | 17,5+1,2 | 2,540,! | 5,6+1,2 
| (ily) | (10) | (8) 
7 000 56 6+ 4,5*| 5,9+0,8°| 50,0+2,8° 
| __ (24) | (16) (9) 
10 000 | 73,62 2,9%) 18,641 §*| 56,6+2,5° 
(33) | 21) | (20) 
| 





Note: Asterisks indicate reliabi- 
lity of difference in con- 
parison to control. Number 
of animals is given in 
parentheses. 


corticosterone, which depended on the 
degree of hypoxia. However, the specific 
amount of free hormone under hypoxic con- 
ditions corresponding to an altitude of 
7000 m showed virtually no difference 
from control value, whereas it doubled 

at an "altitude" of 10,000 m. Thus, 
there was no correlation between concen- 
tration of total corticosterone in blood 
plasma and degree of its binding. 


We compared the dynamics of levels of 
free and bound plasma corticosterone 
under hypoxic conditions corresponding 
to an “altitude” of 10,000 m, with 
exposure for 20, 45, 120 min, and after 
giving an injection of ACTH in a dosage 
of 10 U/kg weight at the same times 
(Table 2). Both hypoxia and ACTH eli- 
cited a drastic elevation of total 
corticosterone level in plasma after 20 
min, reterable to its free and bound 
forms; however, it did not reach as 
high levels after ACTH as it did with 


hypoxia. Preliminary experiments showed that an increase in dosage of ACTH 


in excess of 10 U/kg weight did not elicit further increase in concentration 


of corticosterone [8]. At the same t 


tion of total corticosterone level (it 


ime 


» in spite of such significant eleva- 
rose by more than 4 times with hypoxia). 


the percentage of its free form did not increase in either instance, on the 
contrary, a tendency toward decrease was demonstrable. There was virtually no 
change in concentration of total corticosterone under hypoxic conditions after 
45 min, whereas redistribution occurred between its free and bound forms in 
the direction of increase in the former, the relative level of which increased 


reliably, as did the absolute level. 


level began to decline 45 min after At 


After 120 min, this tendency became even 


more marked, and the share of free corticosterone doubled. Total hormone 


TH injection, while its absolute quan- 


tity and percentage of free form increased reliably. After 2h, concentration 


of overall hormone continued to diminish, and there was also decrease in free 


corticosterone, the relative level of 


which reached the control value. 





ible 2, LI-HCS content (ji2g%) in rat blood plasma with poxi t 10, 
ind atter injection of ACTH, Mtm 


Corticosteron 
ire EE ps 


if al \CTH _[hypox 
yr i 2 ACTH hnypoxla ACTH 
__sahyooxia s Abin jnypoxla | AM 





ry | 17,1+! 3 2,0 Pr 

| (18) (15) 

: 7 sa SNE A . 
| 80,0+4,9 60,2434 | 7,2+08 | 6,2+-0,5 
(11) (16) (10) | 6 | 
| 79,2+3,2 | 55,94+2,7 | 12,6+0,8 ) , | 4 
(12) | (24) | (12) (12) 
(3,02 oe 43,1+2,3 186+ 1,6 | 4.5-+ j- 4 
| (33) (6) | (21) (t 
| 


nus, with increase in concentration of total corticosterone a 1 result of 

1 and ACTH injection, there is change in proportio: tween i rr ind 

forms. It rapidly reverts to normal after giving ACTH, but mtinues to 
with exposure to hypoxia. Perhaps, in the presence of hypoxia, this 

levation is compensatory and adaptive, since it is expr sly the from of the 

rmone that is not bound with protein that is physiologically active. An 


x] 


rund 


nteresting fact is that, in the 20th min of hypoxia and 20th min after injec- 
tion of ACTH, the share of free corticosterone does not char , although the 
tal hormone level rises significantly. In the case icute hypoxia, w 


uld have expected rapid capture and utilization of fre: rmone by tissues 
t experience hypoxia, before the buffer mechani 
octates the protein-steroid complex has time to operat: However, experi- 
with administration of ACTH did not confirm this ) nesis, sin 
ugh intensified utilization of free hormon: r ti iid occur in the 
th min, it applied equally to both hypoxic and normal ies. This fact 
! that binding proteins are able to compensate fo 1 significant 


rease in plasma corticosterone content, capturing ¢! ne in the m 
‘tion as when it is present in a concentration tha! yn t ne-tfourt! 
© >; level. 
th instances, the share of free corticosteron +> min, 
if the body does not experience a need for an in t of hormor 
‘lative level reverts to normal, as it cur 
tion; in the case of prolonged exposure to stress, 

percentage of free corticosterone, as in the cas tia. V. V. 


hikov and A. F. Bunyatyan [9] believe that ther 
ti steroid binding in people under acute and r t 
ter ACTH injection which, in their opinion 
tration of biologically active foims of hormones wit ‘rent reten- 


reserve capabilities of the glucocorticoid syst 


chanisms of protective action of corticosts 


ao f « l ~ + 1 [A . Hi A . ere hve 
IALA nave not peen ldentifle Ma CAd t . if 








facilitate aerobic metabolism, since lactate level i yYpoxl tissues drops 
when they are given [10]. 
In order to assess the compensatory and adaptive role of free rticosterone 
in the preserme of hypoxia, we compared the behavior of the free hormone-- 
hound hormone system in the case of conditioning for hypoxia, when the animals 
were adapted to a shortage of oxygen. The data are listed in Table ”. As 
result of l-month conditioning for 
fable 3. hypoxia corresponding to an altitude of 


Levels of 11-HCS in rat blood plasma 


' tion of total 
after conditioning for hypoxia 





/000 m, there being a normal 
corticosterone, 
served a tendency toward increase in 


concentra- 


we ob- 


ee ————-'-7 th lcosterone relative amount of its free form, which 
xyerimental |. —————— a ene is indicative of possible mobilization 
ations | total | free | bound oF the body's defenses. After 120 min 
171413!) 204021154412 Of hypoxia, conditioned animals showed 
cr | (18) (18) | 5) the same percentage of free hormone as 
| unconditioned ones, with considerably 
ar ee pre eee Peer less total corticosterone in blood 
10,000° an (1). | (go). Plasma. Evidently, the required amount 
litioning | 14,!+!1,0 9+03/)12.9+1,2 of free hormone accessible for utiliza- 
coontae” 49 9. 4 98 Tx 96 843.7 tion is obtained in a more economical, 
10, a2) | (2) (12) rational way as a result of conditioning. 
und after | Interestingly, 120 min after administra- 
tioning tion of ACTH the same amount of total 


hormone yields 


a normal percentage of 


binding, while the normal concentration 
of total corticosterone under hypoxic 
conditions corresponding to an "altitude" 
free corticosterone. Evidently, the 
omplex" is an active process, which is 
for the biologically active form of the 


f 4000 m yields an increased release of 
lissociation of the “protein-steroid c 
‘ontrolled by the body's requirements 


hormone. 


BIBLIOGRAPHY 


t 2 ” ~14 "1 onmnw4 ; +» Dheowod stn 
|. Barbashova, Z. I., “Acclimatization to Hypoxia and Its Physiological 
‘ ? P r 
Mechanisms,  Moscow-Leningrad, 1960. 
~eP / A ar > “ ‘Cp "Ds ‘ ~ 7 j 79 -~ + f S 
», Courtney, L. a Marotta, S. F., AEROSPACE MED., 1 43, 1972, pp 46-5] 
, ’ ’ ‘ , 7 we a ~~" . my , *. ie J . - 
3. Myles, W. . and Ducker, A. J., INT. J. BIOMETEOROL., Vol 1/, 19/3, 
ae ma 
pp Ii~I5 6 
4. Rosevelt, T. S., Ruhmann-Wonnhold, A. and Nelson, D. H., AM. J. Pt IOL., 
Vol 223, 1972, pp 30-33. 
P | ‘ . " . > ~ “ ra « 4% ~ = 
. slaunwhite, W. R., Lockie, G. N., Back, N. et al., SCIENCE, Vol 135, 
1962, pp 1062-1063. 
D- . Vv | Towa tne: T " ] ; . ay 4 ey Lp trubh 
6. Pankov, Yu. A. and Usvatova, I. Ya., in “Metody issledovaniya nekotorykh 
1 "’ [Maehnde nf . es a ¢ 1) -mAnN . nA 34 nro 
gormonov i mediatorov |Methods of Studying Some Hormones i Mediators], 
smee ina : 
Mos OW, 196 Js pp 137-14 ds 





Pavlikhina, L. V., Usvatova, I. Ya. and Bunyatya! » Bee ON 
ARATURE I METODIKAM (1-Y MOSK. MED. IN-I . 167, py - 


neva, G. K., Mikhneva, L. M. and Stani 
"Perekhodnyye protsessy v biologicheskikh sist 
Processes in Biological Systems], Moscow, 19/7/, LO 
», Men'shikov, V. V. and Bunyatyan, A. F., VOPR. MED. KHIMII, No 1, 19/2, 


j “ 
14—-O/ « 


lobin, M. and Perrin, F., CANAD. J. BIOCHEM., Vol 52, 1974, pp | 1-105. 











UDC: 612.014.42-08 
SOME BIOLOGICAL EFFECTS OF HIGH-VOLTAGE STATIONARY ELECTRIC FIELDS 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSHMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 31 May 82) pp 50-54 


[Article by V. V. Antipov, N. N. Dobrov, V. I. Drobyshev, L. V. Koroleva, 
M. D. Nikitin, S. V. Petrukhin, L. A. Semenova and V. P. Fedorov] 


[English abstract from source] The experiments were carried out 
on 345 white mice using hematological and pathomorphological 
procedures. The constant electric field (CEF) was generated in 
a special laboratory device. The exposure to CEF of 50 and 

100 kV/m for 20 s caused hematological and morphological changes 
typical of the anxiety stage of the adaptation syndrome. The 
exposure also produced morphological changes of reactive and 
destructive type in skeletal muscles and different segments of 
kinesthetic receptors. The level of the above changes appears 
to be directly related to the CEF strength. 


[Text] According to existing data [1], there are about 800 thunderstorms 
simultaneously in the atmosphere of the entire globe. If we consider that, 
during this time, there are hundreds of aircraft in the air, it is obvious 
that some of them will be in thunderclouds that carry stationary electric 
fields (SEF) with intensity of up to 200 kV/m. As it passes over earth, a 
thundercloud generates on its surface large induction charges, as a result 
of which the cloud and earth's surface form the two plates of a capacitor. 
and a strong electric field appears in the air, between the cloud and earth. 
Consequently, during flights in the space below thunderclouds, the crew 
could be exposed to this field. 


[There are sparse and contradictory data in the literature concerning the 
biological effects of high-voltage SEF [2-5]. It was shown [6] that the 
results of experiments with animals and clinical observations failed to 
reveal any distinct or consistent findings as to the adverse effect on 
man of stationary electric fields. Biological effects, if they were ob- 
served, have been very mild. 


We submit here the results of an experimental study conducted to demonstrate 
the biclogical effects of short-term exposure (20 s) to SEF of 50 and 100 kV/m. 
The exposure time and field voltage were selected on the basis of the actual 


fo 





quired to fly through a thundercloud and pos 
work places of the crews of modern civil aviat 


EF of a thundercloud was simulated under laborat 

nit consisting of an air capacitor with capacitance C=44, » highn- 
transformer and a set of successively connected type D-1008 

x ified voltage was delivered to the plates of the air ipacitor 
with a Unigor-3P type voltmeter with a type CE-4130 high-voltag id. Aft 
etting on the capacitor plates the voltage required for the experiment, the 
was turned off, experimental animals, which were in plexiglas cubicle-ty 
ayes, were placed in the air capacitor and the unit was turned on for 20 s. 


. 


. 


biological experiments were performed on 345 mongrel femali ice. Int 
series of experiments, performed on 300 mice, we assessed the reaction 
on the basis of changes in the leukocyte formula, leukocyté nt and 
‘ight of the thymus 15-20 min, 1, 5, 35, 45 and 60 days after exposuré 
re was a group of control (intact) animals for each of the tested times. 
econd series of experiments involved pathomorphological examination of 





effects of SEF. The mice were decapitated 20 min, 1 and 5 days after ex- 
re to SEF of 50 and 100 kV/m. At each time, we examined 5 animals from 


group, including the mice in the biological control. The objects of our 
ly were the adrenals, liver, femoral quadriceps and difterent parts of 


nervous system representing elements of the kinesthetic analyzer: nervous 
tem of the shoulder, hip and knee joints, brachial plexus, gasserian 


inglion and anterior central gyrus of the cerebral cortex. We used various 
tochemical and neurohistological technigues. The result f the hi 
cal studies were processed by the semiquantitative meth 


~ 
j 

~ 
! 


Results and Discussion 


matological parameters and pathomorphological stu ( ' lrenal 
iled that, at the early postexposure stages | 


tne ATL IIT i 
: " ee ? a j ‘. , “ 
‘rent in the “anxiety phase’ of the general adaptatior r In rti- 
j }- - - + 
i. - 


15 min after exposure to SEF of 50 kV/m and 1 

50 and 100 kV/m we observed a leukocyte reaction, 
field intensity of 50 kV/m (Figure 1). The leukocyte int 

the range of control values in both groups of animals 5 days after exposure. 


‘xposure to SEF of 50 kV/m, there was a tendency toward de ine of leuko- 
ount on the 35th day followed by stable normalization. |! mnimalis ex- 
to SEF of 100 kV/m, there was substantial decrease in t nt 
35 and 45 days, as compared to the control (P<0.05), but by the 4AOt 
it rresponded to the control level. 
‘sis of the leukocyte formula in the course of th udy revealed that 
e in leukocyte count at the early post-SEF stage primar 
the expense of neutrophils (up to 130-140% of the | t 
se of decline in leukocyte count after the 30th observation d was ¢ i- 
with some decrease in relative and absolute lymp! t Whil 


initial neutrophil leukocytosis could be attributed 





stress reaction, the leukopenia stage 

at the Long postexposure term cannot be 
explained. We see in Figure 1 that the 
fluctuations of thymus mass were in 
different directions from the changes in 
leukocyte conte..t of peripheral blood. 





The reduction in thymus weight at the 





early postexposure stage could be due to 
| release of blood cells into the peri- 
5S 1 § 98 4s 50 pheral stream, while its subsequent 
Time, days appreciable increase could be due to 


compensatory hypertrophy in response to 


Figure l. , 
development of the lLeukopenic reaction. 


Dynamics of changes in leukocyte 


count and thymus weight at different | . £ 
[The changes demonstrated in the adrenals 


times after exposure to SEF (Z of opeept 
, : 20 min after exposure (delipoidization 
biological control). The hatched : : 
: : of fascicular zone of the adrenal cortex-- 
rezion shows mean error for control 7 , : ‘ ; re 
‘ , Figure 2, a, b, increase in activity of 
group of animals (+m) ' hala 
’ , succinate dehydrogenase and NADP dia- 
1, 2) number of leukocytes with by ans) irhetdetnht ateae of in 
; , ; orase) are morpholog Ss - 
fields of 50 and 100 kV/n, P a“ wre oh e 
creased functional activity of the 
respectively 
+ © ua ; - organ, which are observed in the 
3, 4) weight of thymus with fields + let ’ " of tt mht sbebe 
. anxiety phase" o 1e general adapta- 
€ 50 and 100 kV/m, y I & , 


) 


; tion syndrome. The morphological changes 
respectively aol : Sa 

inherent in this state, but less marked, 
were also present on the lst day after exposure (see Table). 


fhe increase in activity of monoamine oxidase, as well as increase in activity 
of succinate and lactate dehydrogenases, acid and alkaline phosphatases in 

the liver, served as indirect confirmation of increased adrenal function. By 
the 5th observation day, the morphological changes in the adrenals and liver 
essentially reverted to normal. 


The demonstrated decrease in glycogen content, increase in activity of succinate 
and lactate dehydrogenases in muscles 20 min after exposure were indicative of 
intensification of energy processes in the muscles. The increase in acid 
phosphatase activity in muscle fibers, which was observed on the 5th postexposure 
day, was indicative of activation oi the cells" lysosome system which, in turn, 
could be due to intensification of catabolic processes in striate muscle 

fibers of skeletal muscles. 


The results our studies also revealed that all of the parts of the nervous 
System we studied responded to SEF with reactive changes. The earliest changes 
(20 min after exposure) occurred in the nervous system of articulations 

(Figure 3). All of the changes were referable to large-caliber nerve fibers 
ind they were the most distinctly demonstrable 1 day after exposure. By the 
9th day, the reactive processes did not spread to new nerve fibers, which was 
indicative of the primary effect of SEF on the nervous system of the joints. 


The findings were somewhat different in the brachial plexus. There, changes 
were found 20 min after exposure, but they subsequently became more marked and 
extended to new nerve fibers. Both the bodies of neurocytes and their pro- 


‘esses reacted in sensory ganglia. Changes occurred already 20 min after ex- 
posure, but were the most marked after 5 days. 





fv 











‘ ‘ 
’ 
' raha 
4 ‘ i ; r } 
‘ A 2) . 
¥ , ’ 7 if y y ’ 
‘ i,j yt 4 i tsi ft 
/ rs | & ) ‘ 
’ ws , 4 ‘ ; 
i i Vv > 
| , 
' ’ 
- ’ 
’ 
- 
' 
+ 5 


--— ~~ - 








Tt 2 ’ | ‘ 
, G. S., in “Elementary Textbook o! 


va, T. Ye. and Krivova, T. L., in "Gigi 
ittviye elektromagnitnykh voln radiochastot 


logical Effects of Radiofrequency Electromayg 


tnov, FF. G., [zrailet, lie Ley Briyedi , Us ; . U6 
, Ibid, pp 128-129. 
ire l, bs Ree tik iarev, A. Ass vorcne . 
tody i sredstva zashchity organizma cheloveka tati 
trichestva" [Ways and Means of Protecting Man 


? 4 


tricity], Moscow, 1968, pp 193-199, 








ee 


~~ 








ide! sucn cCondadltilons,. we hoped tft it a. t 
ild {eld additional intormation. 
f , wt’T ¢ }7' ry] yrneGd Ji $0) MOT ¢ | wl Lt i [ 


. -_ ow ‘ . , 
total-body exposure to SMF with induct ' 
/ y c ’ ’ 
t we’ Ul sed r ] A and P ) \ Ssa¢ Cr< hed 2 0) ‘ 


f 2 \ nd tandard lead using needle PLeECLIOode 


eie Ltromagnel Was on (SP LSA), «cl ter! SH f Ai t 
4 T (SP 115A and SP 5/A), after 3 and 24 h of «+ 
| 





rm | . : . - 
id plottit f variation curv: were perform 
i 
marr nf T. LOO i) y 2 1 , y 1 « ’ 
bh >? 8 >t wt iT) ‘ i VU i Le rol i LTLCL¢é Ai 
¥ ) | 
‘ + ! a" ; ; 
. il tne te . o with prial cd ‘ yy ] Lu wa A/6 : , Se ) 
i is / a & ye , } , 
ic i bicla (4 ng/ 1 ie r ACARwI } WET € hill i ; 
| mn 
‘ 
if ] j ; ~ | ' , ; 
F leads typical changes ir Variati 
; , ; 1 ] . ‘ ‘ ‘ ‘ 
ind several statistical parameters o rdiac rh 
\f ] » 4 > / ’ ] ‘ - 
r¢ 4 Wit ] ction «4 ® ( t 
; > ; , » , , + | | . 
z' ‘ it] ’ il \ Irvé¢ > I . Rida nN I i 
t, . , ; ‘ ; " 
ls. in increase in field ind t Lee 
‘ , 
; a ‘4 ; } ; ; + + ; ; i ’ 
tensiticat n tr the brad irda] : ] 
’ ¥ >? } } . ¥ ; ; 
la a ignt s§ Li G1a re I In &@ an l . 
nn , ’ ’ , a > 
Lilie ri ] C } i ‘ ait ‘ 
; ; " " . 
iia ‘ Ce 
| | , > ? , 
‘ . ; ‘ , pi [ , 
? > 
lic effect, ile in the ot t 
, 4 ; ,¥ Ll ’ j , , , 
> > , 
: >= s , 
| 
' . ‘- 
i itter lz « iu t 
, a? > 
> . 7 | 
w i l } 
, > yy 
J > . 
, , 
i 
‘ ‘ ] aL rt 
? 
5 
> 4 , , 
. i 4 . 
i. * _ 
> r if ‘ | . A 
] lati 








eftect) during continuing exposure to a strong magnetic field and alteration 


otf cardiac rhythm in the opposite direction: biphasi reaction to SMI 


au , 











Figure 1. Examples of typical changes in variation curves (a and b) 
of cardiac intervals in rats exposed to SMF. Here and 
in Figure 2: x-axis, duration of R-R intervals (in s); 
y-axis, incidence 
i: 1) base curve c. control: 


ur 


, 
2) in SMF of 0.4 T, 10 min Ll) base curve 


5) 3 h after exposure 4) after 2/ h 
b: 1) base curve 


2) in SMF of 1.6 T, 3h 
. . 7 
; in SMF ot . », 24h 
4 ,; h irter exposure 
' lysj fF the mear sults enabled | mabe listin fan heatween thr 
, <i Ya LS Ui \ t lt in T¢é shi ‘ ; ena Lt us cto make i istinction ee L wee. Liid & 


periods differing in statistical iaracteristics (see Table). When the 


’ \ . . . - " . ; ~™ * ; ’ 

electromagnet was turned on, there was no change in duration of R- 
. 2d fae . Mand ita ; ' : - reitre ‘ — Pe . —- 
iccording to mean data (M and Mo) but there wa i distinct tendency toward 


increased ariance, ré liable increase in the coefficient of variations va 
ecrease 1n ode impiitude AMo, tension index 11 according to R. M. Bayevs: 
ind autonomic rhythm indicator ARI (according to G. I. Sidorenko ([|14}). 


.ccording to existing ‘onceptions, these changes retlect 1 nonstationary 


» | , 
; ‘ - 
(ft? hil ent ri . iT itt ild icn Ui ent? a4 i if I A i se il . 
i¢ ir? 
' : , an 
: , | , . ss 
R- intervals i ed reliably during exposur F oO 4T, t 
: ‘ } ; . 
hy ¢ ime IoOTe ry mice whe ield ] cion W Cd to 1. l ex it 





" , ’ 
f+} } me ‘ lie. 4 j , > 
it SLO» wil 1 t ‘ ep l Tt) U ARI, wiitsWll , A . i +49 hs . 
, > | , “ 5 
, | ‘ ‘ " , > ~ * 
irt in ned } Ow Lt With prevale ira i L( buf , 
»* ¥ rr ti , rnin yf i ~} ; } } ‘2 ? t ) y rec ’ t ’ ' 
vt il T¢ ‘ u ' sat " ‘ ‘ AU iif Cnanves . a | ~ re i ¢ Mu . 
} —_ . ’ V ’ ) + uy ] ‘ on ’ a ie | 
A ext ire 6 T, as well a . lifter jf i ; 
’ , > ) , - ~e > } , 7 , ; : > 
ut Lor r Nw! ind er irameters reverte l i LS ime, a r 
. r 
in » the mean data, in tne arterettect eT t re wW t hf towar 
— ‘ Ate 
rtening oT Se . Ladi increase | 4 f : if ] as r Yr é 7. 











Results of statistical anaiysis ot 


. 2 ’ | — ° 
. * t+ ’ 
ty | ra eo I Le” o* 
) eé , 
tery turnea LU= , 
’ y fy ; ’ 
i } i] ; j ‘ iwi ‘ 
‘ ‘ = 
‘ i < r ‘ ‘ i ; 
: (4 +) i / \A lo (\4 1t)4 ii» ; f ‘4 ( ) 
pe P<),02 
7 | 
‘ 7 \ ‘ ' ) ) 4 ? és. & f . 
‘ 2 } 109,1+2,4 $e74 ; | 95,62 
| 
‘ ‘ ‘9 } j ‘ 
v' ie: <4 U,1o ivi 14 ,/ 
‘ 444 i | ; 7 = 4 - 
1 wt ? ‘+ | Ol, 0 ‘ ) 2 » 4 ) 
p. {) }« 4 
’ 
‘ ‘ } j '¢€ ) ‘ } ‘ ) 4” ’ 4 4) o ’ ) r 
? t.6 j i é 21,0 eo ? ; +) i.4 ) :.J3 
i i 
‘ ad ) j ‘ ) j i he ‘ 
b + 35 ) ty -U OO >,o0- te 10O~ | +09 24 ~? 
) cw | 
P<—),09 
j 
- ’ 4 / r,4 ‘ ~ 
‘ 7 7 ‘ ’ = 
vid to. isO,4 a4 244,32 420 é' ° J 43'% 2 ~ j ? 
" - 
} , a p« (wil 
j i ‘| f ) | 
at ) + 1y | >, 5 , : P| bes 
tb | i a i | 
! | 
> ‘ ; ites ’ 7 > ' > 
‘ . i »* ‘ ‘ pi AA dS ret C55 t reé suit > , iii ; wi a 8 sa * 
. + fa ‘ , ae * 
'* , 7. 7 j » | ’ a a > . a " ‘ 
i | , A iie LIA ahha ) JiA CL LY i} t were s eu 
° roup. 
"a 
¥ ¥ ‘ , >? rere , , ¥ ’ , 
: . . " Ma ¥ | a 2 ia 4 , i A i . " ‘ P ¥ ‘ i i i . i 
_~ y ’ ,¥ LW4 lie + .¥ > v | y 
‘ rilaviidl ra } Lit ¢ ~ I reast 
‘ ‘ 9 ‘ he . > . > , > 7 ‘ 
. tM aA ‘ a} 4 i , ; ‘ . a s 
>. -* ; an 
, ‘ A if ia ©rid : , ic urve I fer st ‘ 25 r } 
{ , ’ ; , +‘? 
l —_ i i sit Ja , . 
. ’ 1 ie , ’ ¥ , , ¥ ’ 
: . ‘ i a i i i » i * . 
vs ‘ , . . “ae , ; . , , > > - ™ > 
‘ . ; ; at . ii ws ' ; “A Ls ‘ I | s . 
’ ‘ 
I . Cf : I [ | rf | ; a | ’ ~? 4 
‘ ‘ id i . . 
; ° v 4 
, . , i bk Aa re. .~- . ‘ / » a, 
. > ] ‘ 
i " . Ji i , te ad . . i ' 
¥ , - rr , ’ , ’ 4 
21). stati i li . ’ 
‘ . i 7 . , » - , 
: . iis i til . . } i } 
t { «= I I id {t if [ I if i { I } 
‘ ‘ . | ~* ‘ 
I er i) ‘ 
’ ‘ ’ vv ‘ " , 
. _ : ; '- ’ 
° > > ¥ > > , > 
, , i 4 ? | . 
‘ ; ’ ; i . ‘ ‘ 
A * . ? ' : . 
‘ , > ; ,¥ ,* y ’ 
‘ . 








Part rs? 4 . " | | its Wed no rea -_ r MI . rigure 4 {]] istrarts« 
wr ] . ’ ] Ty } 4 
ome typical examples. In the intact rat (see Figure 2d [letter not rendered 
r i , - " Mh ] / me hf i 
in source igure]), . edad to a right shift of the Variation irvé ing ex- 
r iT) ae am int or ; 7 rT} > + > 
i Li pa ] ‘ ‘ ad . ‘ ‘ Si ‘ 
. , , ; , 
AAS aAiré tq, ¥y sit t Li i}  & at the [ ime rhe 
* - " | ‘ 
i Cie cre na met Wal CT i Tl. a im] 1] 
\ ry ar , : if y Di ( ae } rULY 2 led 
\; t left lift of the variation curve 
, 
| : 
. .4 , D ) _* ’ 
‘ r if | fr RR inter 1S and sar p 
4 > . ‘F - ] f 
; ; ipering of the curve (} 6.170.49), 


) left-sided asymmetry (A 2.9520.25; 


/ , } , ve 1 
‘ ’ ' © Pigure <b), there was n reactioi 


CO turning the ele Cromagnet on after 


, , , , 
yr cers + , ' * orrn-e nme 1, ‘ ,* + : ia 7 
, Z1ivVvi ] atropine, nowever, a typical] 
, 4 , '¥ } ‘ y 1 > 
, in the for Or a rigi mart of 
f P . 
4 : ry > . , 
j I 4a 4liOn Cruve was demonstr ible 
'* ,ry MT. t i ‘ T 
‘ } Te | L 
,; | , 
‘ { y 
} le} scyh 1 »} 
» 41tn En, aS we Know, ne rat 
’ ,< vy nim ) > ’ Jon, 4 ‘ + 
j il onu iaministration 
P . 4 ‘ P 
tense itroning filil eliminated the exist- 
ae ° & @ 
’ > ‘ al ‘ f ] . MC 4 rT) rere marr 
, " ~~» ' : hi " 
ak > j ' 
’ . ‘ 
‘ ‘ ry a sar . ,* . La. 4 
— . : P ‘ A A ; ' vai t i ’ | bie & 4 
i? ii ( a i : l ' ° 
‘ ‘4 . , 
' ; y ’ * | 
i ‘ ? ‘ , yet ’ rs a) , wl 
‘ ‘ ' > yt ¥ i \ . iL ¢ : i | re. 
i if 
ri¢ ? r , i ‘ing , ane , 
~~ . ind :. 4» t j ‘ ‘ ; ra ‘ 
’ ¥ . . 
] _ 
‘ ort ita “<c nry , M4 
) > ¥ j 7 ( sure 
Z) in artter ne atror f 
‘ ‘ , J be ‘ etl the resuit 0; nter J 
es , . 
is , . , 
, a. » j jet 7 " an 
,rT roy | . > » ¥ . i . Lue ~ ‘ 
‘ 
4 + . ; ; — - 
rurnine ‘ , an j rease in Datnetic tone : 
Pf i . . 
,*- ; > ] + * 
{ . —* I 7 Vi ieart 
> 
° > 
’ r) rar ’ ' rs ’ ¥ “wr | ’ 
‘ : : 'F ‘ . 
; . ; y ‘ ‘ ré ry YVmnpawth ,. * 
, if ‘ ; 
tf we ‘ in > »4 —. 
. i . LYTi ) iG Lad LO i , 
> . . 
; ’ , ; i; } ~ he ’ } 
irdia r } the 
‘ tear rate i? the 
: .” 
™ ‘ »s* 4 7. o > . 
’ ; ‘ a il it ¢ ) 
| 
4 ‘ : , * 
, 
a , y " ; , ; + 
, ? > ‘ > ~ * . ’ 
i r ‘ r ré Liat 
> ’ , , , 
¥ ’ , ‘ 
: ed 1] ©) t 
>. 
4 , y , ’ ) , ° ° ‘ , | * 1d ‘ 
Li 
, ™ ‘ . ‘ , 
’ ‘ . ‘ ¥ I T 
‘ ’ ‘ ey, 7 ) ? }  ¢ ; ! 
‘ . | ’ 
> fT > 
’ ; 7 ¥ , ‘ 
. : ‘ A f rat ° t . 5e 
, erty ed rmdir 4 > ‘ ’ —_ . } ‘ 
’ 
. : . ’ . ’ * T r Yr ¢@ ’ ] ’ ’ 
; . i . . 








wl and 54.9%42.3%, respectively ind 


+1). 33 and 4.,21°70.254). 


’ - } ' , y ; } 
I} reasead neal tl ratle@e riPYvriile 4 Au 
’ , 7. ' ’ " ¥ 
magnet was turned 1, the ire etized 
i ]  } ‘ | , 4 
and left Sni;rt Tt tne curve, i ] LI \ 
ee ‘ , ‘ : : Fe . 
ert sni¢rt with ira ;t) snortel 2 e5" } . 
; ; 9 wi ? ; > 7 
C* ft reactions lt MF le yell 
’ ; : ry ¢ ; , ‘ y ’ , 
meters, LTi« Ln > é , | 
»* ' ) {mo Y . = ‘ , 
riation puisime ry enabled u } 
t,’ : > j , aa ’ ¥ 
| rune tion. a ag monst r ict i i i ¢ 
™ | , > > 
rit lectromagnet wa turned } i i 
1 4 ‘ »} ly y j } ‘ ,1 , , 
’ iH I S i¢ m3 Ounda i * 4 i ‘ 
r’ tluences on the neart that 
{ ‘ , » 4 ‘ > 
[ ‘ “Na Lilt OT i i , ) 7 ‘ s 
‘ } > iT) ‘ , ext reme , ] > r | F j 
} ! ‘ 
rate ] iS s t it] > ae 
. > + ; , 
etwee ( i A 
> * ) iti t eSlad [ >t ] it * » * 
‘ f 1 gt T r ’ ’ ] ? 
| i * 4 ‘ 
y wy j ‘ ‘ ~4 > 9 ' e 
‘ 
’ . ‘ » } > ‘ 9 ; ’ 
ta 
| 
>. ° * » 
4 ) 
9 | . 
. 
if ‘ ; . ‘ 
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" 
" j . 
} 
s | ’ 
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| 
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a) 
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7 





ie | ne;r if , i « Ve triG ie? STIt eT , . ,é<6 l ‘ia ai ‘ iy I Ltr r i 
’ ’ ’ ’ + Ff ] ‘7 ; ’ 5 | 
‘ » 4 4 " 4 . ot { ; 
po.ley na did OgZICnNesklye Ob yeKCty tfects of Magneti leidcs n 
o4 } > vwartome M4 ‘ QO7 © ’ p12 
DALVUAYU) 1< al / x4 s|, Kaliningrad, 19; Ay 7 c= - * 
4 la : ¥ j ' . ei * P . re mry ‘ 7 , ha’ ‘ ‘ } ) 
. 4 rOvV, . Le a iG nai neva, Le Nes GOD] eG. if l i Ne 7 - , ’ -s 62, 
2 | ( ) } 7 29 
‘ik «Ll, «1962, pp 207-224, 
> as oy 4 ) ‘ s ‘ t! prorcyr [ 7 Vv } ] 
J imenov 1 ; de 1° and Wmjile@, ve Yes rERLOD. BL ‘) ' 9 . i 9 Ly ® 
pp 57-61. 
‘ * _ , ’ . tng ] 10 4 ‘ ree , ‘ vv »e ' " C4 ] } ? " 7 1O¢ 
LU « bile yg Nay i DLlLOLOPICAL mErrects Oo! Magnet ili PIiCLUS, iw rR, LyYOI, 
102, 
} ] Vl di mre , T and Cmirnatv yy Dp VOCMTICU VAVA pT t ‘ 107 
A he ha VVSORAY he hee iJ « and NNUAL VE, Ss ‘* >, L\ (ESKAY 4 ee! *» +' r LJ7if dy 
, >”) 
‘ = 4 & . 
’ r\ ‘* . , corer ‘ ™ P ‘ , } 
Lde 22 er, WU. ke Al Anepton, ‘ o> AL - Peg VOL JI, LIDS, 
) / 
- 1=4QGQ, 
if ' ft ‘ avr i 1 ¢ - ) 
i i 45 . *» bite A So KR, vf ; yt > | JE~— Dil oe 
r ne T Te. AB lw nor we ’ r ,* Ying £ + nteia tl. - 
A ** « t IAN 5 . *@% Ue > mari y ALiOkw | ent VeLe lon mrSsential 1 A _ 
, ‘ ] ‘+ A) ast. ’ ‘es 
eNnSioOn and \ iP TOSCLIeGrOoOSs|1 _ INSK, ivi a. 
, , ; . ¥ ‘ j , * rvr9 , ’ . , . . ‘ —~ 4 
, ¥ . 7, ‘ / . < / 
i . ja . Le . ina AUT ive , ' . Jes i ahded lve d . N, vVi j * s i * 
“~~ ’ _s 
L4oO¥-iG9U, 
? “ad , ‘ 4 j 7 Pn 7 reed nA? : . a: 
i’ . s i ernnk< , Le MK -« it] 4 si it ‘ > , ‘ . ‘ey Lt ld, ¥ ja '* ] / rs 4 Loc foe 
‘ " 
; , 
* . 
‘ * * ai - . ‘ . . . . 7 . ie | 
+ . ow } } ‘ * ts 
. Rh hg bow y jeVve V} ent I i Sl0Oilo¢icail ney itions, Mos< Ws, | he 
1 ,4 j . , . ‘ ] ; f 4 , ] 
i . sal . P , . *“s P’ lt iv a he . ** ‘it ilin Ay . Me ©. ij ** 
' TRER* a’a ‘ ,/* r 7. 





UDC: 629.78:612. 39] 


ME DISTINCTIONS OF NUTRITIONAL STATUS WHEN CONSUMING CANNED MEAT ON 


Cee Oraey tormourty y ? r 
r ws ri ' ‘ SURVIVAL i 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 6 Jul 82) pp 59-68 


Article by I. G. Popov, P. A. Lozinskiy, A. A. Latskevich and I. A. Romanova] 


nglish abstract from source] Variations in the nutrient 

tatus of test subjects who for 5 days were given a survival 
diet made of 400 ¢ canned meat were investigated. The 
energy expenditures of the test subjects were 3000-3200 kcal/day. 
The study was performed under moderate climate conditions. Anthro- 
pometric and biochemical parameters, as well as nitrogen, amino 
acid, carbohydrate and mineral metabolism investigated. It 


li 
as been demonstrated that the survival diet of the above composi- 


, 


= 
m 
sao 
ct 


} ' d hy h Fligh 77 1 { 1 ey 7 
tion can be used by the flight personnel in a contingency situa- 


led that water 


s | 

: 
- 
o 
- 

" 
OQ 


tion under moderate climate conditions, prov 


. . ; 4 . . ° ‘ 
man lw ;  atatkn 7 7 A iV Tne sfud ' . ch 7+ nar a j . hvno=< 
> \4} 4 a a7 sv 4 a / wae ¥ aaa St.UU Y iidadSs Sia Wi’ SWUL aU iL wWDdDoO 
3 4 i / t 
, ‘ , , ‘ . ‘ ‘ } 
mite sail Ee — » — ee ae t losses arlv 
zZiyceni hs intensive Keconemid, neavy Sail OSSC5, and ear y 
* » ‘ ‘ " . ‘ 
ny jr | , on , —a ! + a 5 . + . ‘ YY aa oo 
te i »4 1eT Cc . iA. Sno ild f dAC I int< consider ation whe aa 
. ’ -_ it , P . ’ 
r nots roe . , _y ? sry < aan =" ~ 9 , ar 3.nn miirrtr tert - 3 ry l 
aL iadtix ail it Ut OUVeCla 1 n 5 renadilitat On NUCTItd Li ind pi ot 
° ™ , ’ . ; - . ‘ . . 
a , . > | ‘% ‘ iY > . > > ’ vas . »* . . he .- 9% a m9 . 
raining. is understood that adequate reflignht nutrition may 
‘ ‘ if import ance. 
y = , C { ; > ] [| - --* 
s ‘ . wu al Ta < 
" . 
. = “+ _—, i } * ‘ ~} , + 
ra aC F U I ! iin uecU >» n Wit CarodDOonyaracte 
* ' , 
‘ a ~ , | ’ > + mrt xe ~ + mr » | 
ir, il eis, Oj Se ASCULITS, OCLC. )-e ide! ertain conditions, 
~ r , A + - - + / rr ] , _ > = + 
‘ ; . ré 4 . ‘ c x i ( s ~ ] + ¥ i TI Uti L¢ 
7 ] . 2) ~ 7 7 + ~ 
] 11iti¢ A A ‘ > LT t (ror . d Dit , wa er ante c S ) . n Su¢ 
> ‘ > 74 > ] +4 4 . : } + ; + 44 > 
. y | — . 7. ek 4 4 - ; ” 
icner Di ited CSsti rt es: wnil Od l ] expe Lene 
" , 
> + y —* ; > r } y ‘ ; ‘ 7” 
i i . ] A iti ImStan cS i Sw i ~— uestio 
> , , . ,* 4 a , l_iw »f — , + y > ny b 7 
r ‘ ‘ £ » ~ + t a +E » . . . 4 
. 
> ~ ~e ‘ , . > > * - 5 | 
s ~—» ‘ ‘ idd )T 22 . I it) eme I ge I Lal Iing 
, ‘ ‘ - ‘ + . | 
roun iter esence r é é water sources, etc. r 
’ 7 J - ror ‘ a ‘ > ’ r + > on — i a mn 
* i i | A at . Viltlda mad \ me 
. 
+ . y > . ~* = “~ 7 > 
r, whe is in a imate (par whi the is a water 
v > -_ > + > ,¥ ‘_; as .* an > 7 | ta oe 
‘ : , | A cS “ i 4 i¢€ ; . 4 
‘ > a | . ~- +> s wo . a “ an | ~ . ° > > , 
> * t ~ wo » . lT ‘ + . ‘ eT LO 1S t — ‘ 
, wn! , ] » 7 ? ¥ ¥ ' + 4 > a ? > 
, . A ° P| 4 ici ’ = A 4 . c A 
> > > y errs ‘ oy? > ene —, | ’ nr > ‘ 








nterest is the question of whether it f ssibdie uncer certain 
) 


rr 
. 


litions, to replace the chocolate with canned meat or other foodstu 


we | it here the results of a dynamic study of nutriti al tat > wit 
> > A ‘* 7. a " M C , , } | 
iT FS i a Sul Ji il diet I r ) d iysS, Wri i il LN | 1, CPU ao, © ‘ ” ] iT iceu 
cad , 
\ ‘mom 4 ) ; ; ’ ’ . eae e* ¢ ‘ } rt | _ ’ = 7) aay . 
le av i l nutritiona. status Jas studied LT tne irse Oj] ) qdays, sUTr in 
\w essentiall' healthy Men. 55>—-4U years oft ape, were on emergency rations. 


/ 


nm the tirst day of the study, at 0900 hours, all of the subjects received 


t 
the standard preflight breakfast consisting of 43 g pretein, 46 g fat, 115 g 


ee 
oo 
“~~ 
—_ 
MN 
S 
ad 
- 
~-. 
<> 


irt ivdrates (about 1017 k il), as well as 200 m2 hot tea ;% 


‘ > ] BVT ee rr , ] c } a + . _L¢ o i | + 9 +} ») 4} 
° i1Ke-OT! was inn unced Leo n arter break! ist, ana 17 ter i L er « 
. roar ‘ 7 idea’! es . ’ np i r 1, + mor } L 4 
if) © ii ’ i anc ine Was arino Lt) C7Ul « rrom tn] > baa’ ment on t j{- 4 . t ) 


' —— > > as . ‘ } vad . ‘* i4 > . : ato + «1 ’ > 
med ONLY Lhe ror ds in tne emergency diet Lor ) days, wnichn consisted Oi 


} ‘ — , a 7 M ’ . j A > 
nr > ad ’ | no ‘ r “7 7 r . , Lc r 
4\J : i 1¢ 4 t | " i \ it y wl | aiso 7] ¥Veii é - water Jt r Gi ive . in X i 
} 4 
' , Pt Wr flan +t - 9 T SB Dh 2 = ry - , 
x1 in rar. we ur cans OI Holied Des ( tL JLZ05—- 90. eal 
" : ‘ . ; 
j y ‘ } > -_ t / - > Aas T1h1\0\ -« > ~ * i+ <4 ar - 
wads a ACU ae | YU) A > a CanS. nracn f in COntCaLINned a\/ leat consti 4 ai in 
~ . ~+ 7 & ] ) o '*} »>Q - ¢ > in l 2 . ‘ > = / 4 7 > »~ b ‘ 
iVel int A & A rn i , WALtI a 4 > ro t bag e a eels Je i , ‘ : } ’ it ite ~ F 
ho ann 7. Q . s , . om T «oe on + . 1 C+ da‘ t *} . r > ' 7 v ate ha 
| inned it was used oniy on ie 2a Ct nae iyvs a e rate i | [ 
» » , . , 5 , 
; “y) > > = + j + 4 > ’ 7 , + ‘; 1. , + - Yr , y? 
ay. 1 the first day, the subjects were limited only to the preflight 
» > + > T > ‘ 4 ‘- L } 7 ~~ > j ~ 7 > . : 7 r) > 
eakia ° ine ;O0GC intake scneaquie nrorme to the requirements oi 
: 
; . , . + 4 + - roe 9 v * 3 + > - = >. 
ifety. lt i orbidden to store ope ans at positive temperatures. 
* P . 
, > ; y . \¥ > - me ae Mas . + ‘orwn" + =o “a? 
> it iSs\ , co I vat iZe medi iiaCe il t A595 A nour A'\AL ALLE it 4 wih 
it w r rv to open |] an (190 @). which divided am 3 sub- 
ee | ® AA was l¢ t 5a ( pen 2 Cat LJU ¢§ » WniIicn Was i1i1videc i Ii} , iv 
+1 >) ; ; 7 »} »} 
’ a" — y+) + > 2. vy | ‘+ 7 + Ff an ie a . r . a 
5 9 Ail Lif NOTNANS > A LT) 1©@ da i e anc i le@ evenine. LiClwis 
. 7 4 . e "| ‘ . . ‘ ‘ 
“+, " Ne ‘ | . > . is - 4 ¥ 
“« iLU ive idadUu 4 eat 4 Wwe a i y «@ A iat i i Jaiue i eaCn) edaa Oil 
; hod ] , a ~ 4 t SA }. yt ? } (7 . : iin .y : ‘ at) ye 
s : » ao ALLE b > AX & cu iD¢ li é Fr ii oJ b/ 4 JL a ly “~.- x AGat . Ahk AilZ 
. : e 4 . : e « ° : ‘ ; * ° , , 
> > . > - . 7. i | +> a. . . . > ~~ 5 whee 4 . aan ~ > - nl ‘ , | ‘sf? 9 
perl 4 iid Ui ne sud ‘ > SPOS Se Se ees 4 wi = elii so jai aictiv a & i‘ 
— . S mes lesan (Or . . - free whe 14a¢ ro ££ 10 fy ) L a1 , a . and incioce 
Viid iiv i t P| aveTave ose & ee Y CAI nN 4 LLUE ( i = d r i/jUday aii Lt) at 
> . 7 — > : o : —_~ a eb : . 4 
] i ¥ySi 211i exertion )é use I tnelir entail work wnicn was aone 
+ . j 7 y . o™ . + nated - ror > . » 7 ‘ = oy + 
i A 4 , é . © c ait sku A | A i ft oP: i | i | at 
’ . . 
, ; + 4 ~ ine os eer ; anny na j 
} l = 51 Nai Spring-summer eriocdc, in app!I i t i ¢ 
‘ . ° j . ‘ . +s 
> > ‘ > > > . , ; + > + ,r 4 y . > . , 
] ; L t | 1OW- 1iOT1L¢€ it wi i rT ¢ £ A s i pI i «Wes it 
i» + 
. 
, . ; 
, ; - > y ’ > ; -- ‘ + . ; ‘ 
‘ t LT iramecters i IUCTIitisé id iS; “ l 9 
j _- —_— ~~ <4 _. ' - = + > , -o . ; wo _ 
lvydar., i i | imino i LUD, excre i Ai ia ] r¢ eT 4 ai 
; . +4 ‘ ¢ » ° 
y " ¢ . = yxy dor +} -, +t75 =" ; , “wr > ; +*hirc? re (me rz 
‘ c c . “7c OU sc U cil weida elntis , ippe¢ AL& » Ai , VU A A " 
‘ ow 9 - - ‘ . y 7 [+ > ‘ re — 1, 9 7 . ‘ . 
ie termined I > WOrK CaDdDacl I i] ind iC KF isc ies i¢ 
: , . +4 , 
j ’ . ~ ‘ . ; ’ 4 *} ‘ ° ; 
etr . Perio illy, we took a indard leads. 
‘ r } | ’ 
i A i A 
, > > + ‘ ; ~~ 4 , " ‘ ‘ + ’ " > 
f n es i I imd je termi é f we] 





(S6' x6) 


SS 4 


9») 
Q01u3ad 

AH BAODRHY 
40 AWQA HAG 


NO AHO IAM 





“4HOIGM 


on 


“IWAYMON 


OSGNSANODS4 








(Co'C6) 
OL TL 
(i2°¢6) 


Se IZ 


bea 

- 

> 
— 


9»! 


“SNOIAWS) 
AQDNZOYXSNS 
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nstantly over the 5-day period due to the quantitative insufficiency ot 
1. While the subjects maintained an average daily energy expenditure of 


] 1 } \ } al 4 f a 
-3. kcal per 70 kg weight, they received about 1090 kcal in food on 
1 


4 } , , f | 1 als . 7 . 1 ) Fr i 
tne tirst da (pre! light breakfast alone) and about 2 kcal/day for the 
next 4 days in the form of emergency rations. Maximum weight loss occurred 
, ' ; 1 M Mf A f } ; > . > v 
in the lst-2d days of the emergency situation :; 4 subjects lost the most 


yn the 2d day, 2 on the Ist, 1 lost virtually the same amount on the lst 
ind <a days. Evidently, the fact that the calorie shortage was le 

the first day played the decisive role, because of intake of the proper 
pretlight breakfast. On the 3d day, all of the subjects lost less weight 


than on the 2d day of low-calorie diet. 


n bsequent days, weigiut loss continued and in most subjects it was at 


1 minimum tor the 5th day. Average (m) values for the group of subjects, 


14 fo. Pah ramet 4 ine LA day 
ini e listea in Table 1, contirm the foreyoing. In the lst to 3d days, 


: ; ’ r IFT We Mawin 7 ol 7 ma Fy, ‘ +} sah 4 . 
Li¢ 9Cituted J./—dI.-Z2/ KBLeo Maximum weight loss was found in the subject 
» wel the ost itial] and minimum in the one who weighed the least 
} TY") or 4 ] 7 Soh 7 o an = ~4 _ +1} . K406 > 74 i‘ 
it the start. ine percentiie weight ioss was greater in the subject wit 
. ot a4 1 | “a 4 ol | : 1 sate 4 caf @] ’ + —~ F . . a }, 
a; it st l it lai WeiPnt tnan LTl tne sud ye t Witt A ' WOES L We ight prior to lic 
, ~ 4a , : " I ea 4 ; . . > vl ee a | }, 
nergen Situation. How er, this patte rn was 1iot observed in tne 
> : , T c ~ ’ “ant la ht ] sw ; foun } in sah 4 + 
‘ > . . i IMs axl WeltlUCliitclid w ¢ i LU as A 4 U ae! Ai Lil je. L 
f ! +h , . ol } }3 boa lec 3 = wh 4 ane -ov who sho red 1 loss of 
= . hy WI! ) Clipz 4 5% 4 L©es5s Lildail OU 1s 5 \ Wii »>flLOW RC a LOSS Vi 
; + , + + t v.7r 7 cy’ ae! | cc 1 ad , W ) yh © ] Cc 
. A Wel; . ] joerc Ll S» WNO Wel#ene even C >» :cal CAiakiit L \ » 
, — T"} hes 17 FE os T } i | 
6.19 i the a value in 5 days. he individual differences in dail’ 
7 + 5 | 7 f ] ] nN 
> ~ y , . - ! cy 
iO: > re ij ed - lL 111 1¢C int On) t st 4 — & ) gay ,« Lz ) jes . ) on is ~ © UT) 
; > + > -~4 + 4 + 1 . 17 ‘ } 7 ] Lo ] ‘T) 
LV, e Tluctuations oO welgnt 3s onstitute ~4-i.ei KE and ¢ 
f : 
t . > | . y= 5 . | Ls . 
ss under emergency conditions could occur due to tissular structures 
‘ Son 4 . ae } . 1 latheA se 1 'Iindar anaAdsetana 
I tining nutrients an is a result or denydaration. naer our conditions, 
, a . ] 1 nt ante ate 2 a 1 ; 2 69 : . - 
c c { t Cé , eTacure was LOS©¢ to C lt COT rort if le i ¢ yom @ fluid | >o Snoulidad 
. 7 . ong ¥ fan } EF A 
i irrex leriy due CO imperceDtl Le pe liration and diuresis. At 
rtable temperature with constant increase in imperceptible perspiration : 
! 7 
: t , + - > ¢ 
l jue to i1LUTé lS WI1LI tneé cnanege LO LOW-CaloOrie diet ¢ l 
. Po ¢ rt taea Tr 1 #4 + } ] loaod | id lance live «6TH ijiur cic 
east if} pal A lial OTl Lilt e >t Ada p ° qeeaqd, [iUla iOSS aQaut LO Gd eSis 
, 1 1 call : P } . a maew a4 1492) @& ‘ 
Aa Li Wie ii Ai i ui +. t Ny cil f it irted t < merven»nc qai1et: 4,UKl1] ™ \ 
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the t iy, SSO t ] ym thie ind O to 1010 m& on the 3d. in the 
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fable 2 lists the results of testing the subjects’ blood sugar. Blood was 
taken from a finger dally, on a fasting stomach, at 0900 and 1600 hours 
welore eating. We assayed glucose by the glucose-oxidase method as modified 
by I. S. Balakhovskly, in which a concentration of /0+10,/7 myZ was considered 
normal [3], which Is o te close to normal levels when using the usual clinical 
modification of this wethod=--56-94 mgZ [6]. With developme.t of quantitative 
insufficiency of food intake on the low-calorie diet, all of the subjects 
presented a gradual decline of blood sugar level. Signs of sporadic hypo- 
glycemia began to be demonstrable on the 2d day of the low-calorie diet. On 
subsequent days, they became more frequent and more marked. On the Sth day, 
signs of hypoglycemia were found in virtually all of the subjects. We were 
impressed by the wide scatter of individual readings. At the end of the 
low-calorie diet period, lower levels were noted more often in subjects 

who weighed less initially. On the 3d day after the test hypoglycemia was 

no longer demonstrable. Thus, use of 400 g of canned meat for 5 days was 
associated, sturting on the 2d day, with appearance of sporadic hypoglycemia, 
the cases of which increased thereafter. 


Table 2. Dynamics of blood sugar levels with intake for 5 days of an 
emergency diet consisting of canned meat 





_—— — ee 
































z 9 | MLOOD SUGAR, MG% 
J- a. } NAY ON EMERGENCY OIET | THIRD DAY 
<Pede | — EE Ye wer eee Eee ———————sl ATER 
SUBJECT ercea| =. _| ae : = 7 = ‘ , _| 5 STUDY — 
tte 9| > | 3 | 8 ° El > | & | o | @ he ° z 
eseer-| - | « lel éls lel]? ei « Si é 
eleleleleleteletele] |e] s 
} ' a : . . | 
S-Ov 17,8 | 90 | 86 | RA 15 77 72 D fi ‘ 44 55 | 68 a) 
L-ly 9,7 BA “4 4 70 | 69 | 77 66 | ol 46 o4 é 76 
K-YAK 2.1 74 | ib 63 | 3 5A 46 5A ah 6, 44 ie) 52 14 7 
A-OV 10.6 | 66 | 78 | 63 | 64 | 60 | 54 | 69 171 | 63 | 56 | | 74 | 6 
L-1ICH 7,7 90 | 96 | 85 63 | 67 | 65 |77 | 62 149 | 55 | & | 92 HY 
SH-S 2,05 | 4 | 8 | 87 | 4 173 | » |46 149 1439 | DW | w i 
PIN io | 7 | 12 | 61 158 146 | 50 | 148 152 150 154 172 | 74 
































Note: On the 6th day, we took blood on a fasting stomach, 1 night 
after the last "emergency" supper. 


As a rule, on a low-calorie diet there is increased synthesis of ketone 
bodies, accumulation of which in blood and concomitant acidosis are consid- 
ered to be among the principal causes of worsening of well-being [7]. 


We tested excretion in urine of ketone bodies using a modification of 

the method of Elber and Bonnamour [3] and found that, in the base period 
and or t'.e lst day of the emergency diet virtually no ketone bodies were 
demonstrable in urine. On the next 4 days, ketone bodies were present in 
urine of all subjects and presented a tendency toward increasing with 
development of quantitative insufficiency of food. On the 2d day, 0.118 to 
1.053 g of ketone bodies were found in urine, on the 3d day 0.849-2.039 g, 
on the 4th day 1.075-3.582 g and on the Sth 1.848 to 3.451 g. Asa rule, 
ketonuria was higher on the 4th-5th days in overweight subjects. In the 
comparative aspect, ketonuria on this diet was higher, particularly on 

the 4th-5th days than on a low-calorie diet consisting of 300 g chocolate, 


93 








in which case there was daily intake of carbohydrates [6]. Thus, starting 
on the 2d day, when the endogenous supply of glucose and glycogen had 

heen essentially used up, there was active and increasing utilization of 
endogenous lipids. The proteins taken with the canned meat could not pre- 
vent ketovemla, apparently due to the limited intake with the emergency diet. 
In addition, intake of ketogenic amino acids, protein and fat on the meat 
diet was inatrumental, in turn, in intensive production of ketone bodies 


[9-11]. 


fable 3 Lists the results of assaying 17 free amino acids in the subjects’ 
blood plasma before and after being on the low-calorie meat-fat diet for 
5 days. These studies were made using the model KLA-3B Hitachi automatic 


analyzer, 






































lable 3. Blood plasma free amino acid levels in subjects (n = 6) who were 
on a low-calorie meat-fat diet for 5 days 
. CONCENTRATION, mom __lenance 7 
tT NTRATION 
FIRST DAY END OF FIFTH IN FIVE DAYS 

FASTING AT DAY, FASTING : 

AMINO ACIDS 0800 HOURS aT 0800 HOURS % OF INITIAL 
[erant ov) | stare 

ESSENTIAL AMINO ACIDS 
LvYGINGe 4,06+0,17 3,92+0,08 96,5 
THREONINE 2,13+0,01 | 82+0,07 85.4 
VALING 2,36+-0,10 2,.79+-0,04 118,2 
METHIONINE 0,36+0,04 0,44+0,07 122,2 
Lrucine | ,44+0,05 2,92+0,10 202,7 
ISOLQUCINGE 0,72+0,11 | ,61+0,04 223,6 
PHENYLALANINE 0,794-0,14 (),96+0,08 121,5 
NONESGSENTIAL AMINO ACIDS 
MIGTIOING 1,29+4-0,07 1,41+0,03 109,3 
ARGININE | ,36+0,12 1,04+0,11 75,4 
CvSTINEe 0,69+0,13 0,57+0,16 82,6 
ryYnosine ),90+.0,02 0,964 0,07 106,6 
ALANING 2,44+0,11 2,07+0,03 545 
AGPARTIC ACIO 0,13--0,04 0,15+0,06 115,4 
GLYCING | ,38+-0,03 1,74+0,06 126 
GLUTAMIC ACIO 1,51+0,06 | 40+ 0,06 119,2 
PROL INE 2,26+0,10 2,07 + 0,04 91,6 
oening 1,59+0,12 1,74+0,09 111,9 
TOTAL AMINO ACIOS 25,43+0,75 28,31 +0,59 111,3 
TOTAL EGGENTIAL AMINO ACIDS (€) 14,53+0,81 16,91+0,62 116,4 
TOTAL NONESGENTIAL AMINO ACIOS (N) 10,9+0,61 11,4+0,57 104.6 
E/N RATIO 1,33 1,51 














During the period preceding the emergency diet, most amino acids were in 

the range of the approximate normal levels cited in the most recent, 3d, 
dition of BME [Great Medical Encyclopedia] [12]. Aspartic acid and cystine 
were the only exceptions, since their concentrations was below the cited 
"norm." As compared to the “physiological norm" cited by N. V. Semenov [13], 
most amino actds were in the range of normal physiological fluctuations, 

but lysine, threonine, serine, aspartic and glutamic acid levels were 
elevated, while cystine and alanine levels were somewhat low. Consequently, 
on the usual diet prior to the emergency situation, intake of most amino 


94 








acids and protein can be cvaluated as quite satisfactory and even high. 
Somewhat .ower levels were found in this pericd only for cystine and alanine. 
As for aspartic acid, the "norm" cited in [12] appears to be exaggerated, 

as confirmed by data of other authors [13-15] 


Under ordinary living conditions and with a satisfactory diet, the concen- 
tration of amino acids in human blood plasma is stable. A serious effect on 
metabolism is required to change it. A low-calorie diet and development of 
both quantitative and qualitative starvation could be such a stress factor. 
This is confirmed, to some extent, by the change in plasma amino acid levels 
{n our subjects. 


After 5 days on the low-calorie emergency diet of canned meat, according to 
the mean values listed in Table 3, the subjects showed an increase in con- 
centrations of 11 amino acids and decrease in 6, as compared to their base 
levels. True, the levels of most amino acids remained in the range of 
physiological fluctuations listed in [12]. The exceptions were isoleucine, 
the concentration of which exceeded the "norm," as well as cystine and 
aspartic acid which, as before, showed a low concentration. A comparison 

to the "physiological norms" in [13] revealed that lysine, threonine, serine, 
aspartic and glutamic acid levels were elevated, as in the base period. The 
concentrations of leucine and isoleucine exceeded the top of the "normal" 
range, while alanine and arginine were below the "norm."’ The most appreci- 
able change in the direction of increased concentration was referable to 
leucine (2-fold) and isoleucine (2.2 times) and in the direction of decrease, 
to arginine (to 10/13ths). 


There was an increase in total essential and nonessential amino acids in 
the 5 days on a low-calorie diet. The ratio of essential to nonessential 
amino acids increased, mainly at the expense of increase in essential amino 


acids. 


The data listed in Table 3 concerning the dynamics of plasma amino acid 

levels must be analyzed with consideration of both the nature of the low- 
calorie diet (protein and fat with virtually no carbohydrate) and activation, 
under these conditions, of gluconeogenesis and formation of ketone bodies 

for the energy needs of the body. After exhausting the supply of glycogen on 
the first 1-2 days, there should have been intensive development of gluco- 
neogenesis, primarily at the expense of amino acids (exogenous and endogenous). 
Concurrently, there should have been production of ketone bodies from amino 
acids and lipids. The presence of an intensive process of formation of ketone 
bodies in the subjects was confirmed by the above-described dynamics of 
ketonuria. According to current conceptions, most of the amino acids we 
assayed are glucogenic (or glucoplastic), particularly alanine, glutamic 

and aspartic acids, as well as threonine, valine, glycine, arginine, histi- 
dine, proline, serine, methionine and cystine. Isoleucine, phenylalanine 

and tyrosine are considered to be glucoplastic and ketoplastic, while leucine 
and lysine are considered ketogenic [9]. 


Taking the foregoing into consideration, some hypotheses can be expounded 
with regard to the demonstrated dynamics of plasma amino acid concentrations. 
The increase in plasma levels of glutamic and aspartic acids, valine, glycine, 


95 











histidine, serine and methionine is indicative of active gluconeogenesis due 
to these amino acids and presence of some supply thereof in the body. There 
was considerable tntensification of gluconeogenesis because of the virtually 
complete absence of carbohydrates in the diet and regular intake of amino 
acids on the emergency rations, even though they were present in small amounts. 
The decrease, under these conditions, in concentrations of alanine, arginine, 
proline, cystine and threonine could indicate that, by the 5th day on the 
low-calorie diet, the most labile stock of these amino acids for gluconeo- 
genesis was largely utilized, while intake with food was too insignificant. 

A comparison to the "norms" of N. V. Semenov [13] will easily convince us 

(iat expressly the alanine and arginine concentrations were low in this 
period, which could be indicative of gradual development of a deficiency of 
these amino acids. The levels of glucoplastic and ketoplastic amino acids 
(isoleucine, phenylalanine and tyrosine) rose on the 5th day, which was 
indicative of development of both processes and presence of some reserve. The 
concentration of ketogenic leucine increased, and quite significantly at that, 
which is indicative of the active participation of this amino acid in formation 
of ketone bodies. At the same time, there was a decrease in concentration of 
lysine, the supply of which apparently began to be depleted by this time, 

and not enough was taken with food. 


Table 4. Excretion of total nitrogen (g) in 24<h urine before, during and 
after intake of low-calorie emergetcy rations consisting 
of canned meat 





—_—— —_—_ —_— 


RECOVERY | usuac 
PERIOD | DIET ON 























| USUAL LOW.CALORIE DIET OF CANNED 
| 1€T AFTER FIFTH 
DIET, MEAT, DAYS CESSATION DAY AFTER 
SUBJECT OF BEING ON 
| DAYS \EMERGENCY) EMERGENCY 
_ BOIET | RATIONS 
. - + -_-—_—+---— or = om = | 
_ 1 5 2 | 1 2 1 3 | 1 3 | 4 5 | 1 3) 1 3 
' 
S-Ov 16.16) 43,301 13,20) 15,23 ]14,82143,.25]14,886] 12,60] 70,82 13,20! 16,77 14,47 
Kelty 15,16) 93,151 94,00)43,73)15,76)43,51114,51114,58)72,60] 11,97) 14,01] 13.64 
K-VAK 15,091 16,20] 14,27] 16,68] 15,42] 46,57114,00] 13,60) 74,17112,96115.97]| 14,00 
Ay, 15.12113,46)12,43'15,221 16,371 44,02115,06113,18172,24112.46114,00] 15,96 
TAS 16.25) 15.58112.34 14,15115,15141.64114.90113.471 70.01 112.15} 15.85] 15,16 
~ 5. 16,315713,40, 14,37116,.74144,51113,30113,88171,.69112,.001 16.46 15,50 
P-N 13,33 }16.15])12,72 14,40115,47142,59114,61113,99171,90114,.35115.33] 13,49 
Mem 15.19 + 114.46 + 113,19 = 14.63 + 115.68 + 13,73 > 114,49 + 113.61 + 171.839 = 112.45 + 115.54 =] 14,602 
0.41 | 0,42 | 0.v7 | 0.415 | 0,27 | 0.69 | 0.24 | 0.26 | 0.84 | 6.43 | 0.40 0.34 
Ms” las 14,22 13,87 12.56 13,86 —]15,05 —|42.16 13,92 — 113,00 69.67 - 112.05 - 14,60 — 13.186— 
16.16 [15,85 115,62 115,80 [16,31 [143,36 115,06 |14.22 173.99 [!3.61 16. 48 15,40 
































Table 4 lists the results of assaying total nitrogen in 24-h urine of the 
subjects. Nitrogen excretion in urine when on an ordinary diet was indicative 
of rather high supply of food protein. Aiready on the lst day of the low- 
calorie diet, most subjects showed a decrease in total nitrogen in 24-h 

urine. In most cases, nitrogen excretion in urine was higher on the 2d day 
than the lst, whereas in half of them it was higher than in the base period 

on the day before the “emergency situation." For 3 days, nitrogen excretion 
continued to increase in 5 cases (i.e., the majority of subjects): it was 
greater in all of the subjects than on the lst day on the low-calorie diet 

and in half of them it was greater than when they were on the usual diet. The 


96 








mean values for the group of subjects confirmed the fact that, after some 
decrease in nitrogen excretion on the lst day of the “emergency situation," 
there was an increase in nitrogen excretion in urine on the 2d and 3d days, to 
the base level or even above it. Overall excretion of nitrogen in urine 
constituted a mean of 43.73140.69 g for the lst-3d days. Maximum excretion of 
nitrogen was found in subject K-yak (46.57 g) and minimuminL-ich (41.64 g). 
Considering the relatively low nitrogen level in the emergency diet, it can 
be concluded that there was development of a negative nitrogen balance and 
active utilization of nitrogen-containing substances in the body already 

in the first 3 days, primarily for gluconeogenesis and compensation of 
expended energy. Excretion of total nitrogen began to decline on the 4th and 
Sth days. While it averaged 15.68t0.27 g on the 3d day, it was about 
13.61%0.26 g on the Sth. In most subjects, excretion on the 5th day was 
insignificantly greater than on the lst day of the low-calorie diet. Conse- 
quently, the magnitude of negative nitrogen balance diminished on the 4th-5th 
days. This was due to diminished utilization of nitrogen-containing body 
substances for gluconeogenesis, apparently because of depletion of readily 
metabolized and more accessible supplies, primarily of free amino acids and 
protein. This is confirmed to some extent, by the dynamics of plasma amino 
acid levels. On the 4th-5th days, the subjects apparently made increasing 
use of fat supply as a source of energy, which was confirmed by the 

more intensive excretion of ketone bodies in urine during this period. 


On the whole, excretion of nitrogen over the 5-day period constituted 
71.83*0.84 g. If we add to this the 6.76%+0.22 g nitrogen excreted in 5 days 
in feces and sweat, according to estimates we cited earlier on the basis of 
FAO/WHO data [14], total nitrogen loss in this tim constituted 78.59 g. 
Nitrogen intake with food constituted about 21.6 g in 5 days. Consequently, 
of the total supply of nitrogen in the body initially, 56.99 g was lost in 

5 days. The amount of endogenous nitrogen lost in 5 days constitutes only 
5.7% of the normal nitrogen content of the human body (about 1000 g), which 
is substantially less that the critical loss of 50% nitrogen associated with 
starvation (as a result of breakdown of 40-45% of the protein contained in 
the body during starvation) [4]. Consequently, after 5 days on the low- 
calorie emergency diet of canned meat, the subjects presented only the 

early stage of protein deficiency. Interestingly, with use for the same 
period of time under analogous conditions of a carbohydrate diet (300 g sugar) 
nitrogen loss constituted about 5% and on an emergency diet of chocolate 
(300 g) it was about 5.2% [8].* Nitrogen excretion in urine was virtually 
restored to the base level on the 3d day after the subjects changed to the 
usual diet. 


Daily excretion in urine of macroelements (potassium, sodium, chlorine and 
phosphorus) gradually diminished over all 5 days on the low-calorie diet. As 
compared to the usual diet, there was maximum decrease in sodium (to 10/69ths) 
and chlorine (to 10/63ds) excretion over the 5 days, to a level that was 
substantially below the accepted physiological norm. Excretion of these two 





*The calculation of nitrogen balance in [3] did not take into consideration 
intake of 6.88 g nitrogen in the preflight breakfast, as a result of which 
a higher percentage of nitrogen loss is cited. 


97 








elements diminished the most on the lst day due to change to a diet with low 
NaCl content. While there was excretion of 3380+185 mg/day sodium and 

4499498 mg/day chlorine in urine on the usual diet, on the first day of low- 
calorie diet sodium excretion diminished to 25791141 mg/day and chlorine to 
»582*299 mg/day. Sodium excretion constituted 1113+86 mg on the 2d day, 

994+*53 mg on the 3d, 614%67 mg on the 4th and 488+77 mg on the Sth day. 
Chlorine excretion dropped to 29611263 mg on the 2d day, 1794108 mg on the 3d, 
14527148 mg on the 4th and 13491146 mg on the 5th day. There was insignificant 
decrease in sodium and chlorine excretion on the 4th-5th days. During this 
period, in view of the danger of desalination of the body, there was active 
renal retention of sodium and chlorine, 


There was less marked decrease in potassium and phosphorus excretion. On 
the Sth day, 24-h potassium excretion was 10/17ths the base level and 
phosphorus 10/2lsts. Potassium excretion dropped below the accepted 

norm of 2-3.3 g/day. We were impressed by the relatively slow decrease in 
potassium excretion and even an increase on the 3d and 4th days. Ona 

usual diet, potassium excretion constituted 2469+146 mg/day; it dropped to 
1989*11 mg on the Ist day of the low-calorie diet, 17581115 mg on the 2d, it 
rose to 2193+*175 mg on the 3d, decreased again to 19892249 mg on the 4th 

and to 1420%109 mg on the 5th day. Phosphorus excretion in urine when on 

an ordinary diet constituted 1053144 mg/day; it dropped to 773138 mg on 

the lst day of the low-calorie diet, rose to 908+59 mg on the 2d day and 
continued to decline thereafter: to 713+53 mg on the 3d day, 557+50 mg on 
the 4th and 510+42 mg on the 5th day. There was little change in phosphorus 
excretion on the 4th and 5th days, and it was at the bottom of the normal 
range. Thus, with intake of emergency rations consisting of canned meat 
there was gradual developmentof shortage of macroelements, particularly 
sodium, chlorine and potassium. However, jugding by the subjective condition 
and EKG data, the situation could be assessed as satisfactory by the end of 
the 5th day. 


The results of our studies warrant the conclusion that, with limited expendi- 
ture of energy (3000-3200 kcal/day) and fluid intake of up to 1 2/day in 

4 temperate climate, a diet consisting of only 400 g canned meat, which is 
presently used in PEP, can be used for 5, let alone 3 days, as a low-calorie 
emergency "survival" ration. At the same time, it must be taken into con- 
sideration that such a diet does not preclude development of the early stage 
of protein deficiency, sporadic hypoglycemia, marked ketonemia and progressive 
lesalination of the body. All this must be borne in mind when training 

flight personnel, organizing rescues and implementing rehabilitation measures. 
The fact that this diet does not quench hunger entirely and, in a number of 
cases, even increases appetite, as well as the possibility of more intensive 
thirst, are among the substantial flaws of such a diet, when it is used 
regularly 3 times a day for 2-5 days of an emergency situation. Moreover, 

the 100-g size of the cans of meat makes it extremely difficult to consume 

the contents in divided portions, particularly at positive temperatures. 


The possibility of using "survival" rations of this type at high ambient 
temperatures and even greater limitation of water requires further investi- 
gation. The results of our study confirmed the previously derived conclusion 
[3, 8] that a good initial nutritional status is of positive significance 


98 











for successful "survival" on a low-calorie diet under emergency conditions 
and that proper preflight nutrition plays an important preventive role, 


l, 


BIBLIOGRAPHY 


Isakov, P. K., Ivanov, D. I., Popov, I. G. et al., "Theory and 
Practice of Aviation Medicine,” 2d ed., Moscow, 1975, pp 107-109. 


Volovich, V. G., PROBLEMY KOSMICHESKOY BIOLOGII, Moscow, Vol 30, 
1976, pp 36-40, 90, 134-137. 


Popov, I. G., Lozinskiy, P. A., Latskevich, A. A. et al., 
KOSMICHESKAYA BIOL., No 3, 1982, pp 16-25. 


Veselkin, P. N. and Kaplanskiy, S. Ya., in BME [Great Medical 
Encyclopedia], 3d ed., Moscow, Vol 6, 1977, p 295. 


Pokrovskiy, A. A., "Talks About Nutrition," Moscow, 1964, p 140. 


Kolb, V. G. and Kamyshnikov, V. S., "Clinical Biochemistry," Minsk, 
1976, p 119. 


Logatkin, M. N., VOPR. PITANIYA, No 5, 1963, pp 27-33. 


Popov, I. G., Lozinskiy, P. A., Latskevich, A. A. et al., KOSMICHESKAYA 
BIOL., No 1, 1983, pp 21-30. 


Orten, J. M. and Neuhaus, 0. W., “Human Biochemistry," Saint Louis, 
1975. 


Gorodetskiy, V. K., in BME, 3d ed., Moscow, Vol 10, 1979, pp 851-852. 
Joung, V. R. and Scrimshow, N., SCI. AM., Vol 225, No 4, 1971, pp 14-21. 
Balakhovskiy, I. S., in BME, 3d ed., Moscow, Vol 12, 1980, pp 108-109. 


Semenov, N. V., "Biochemical Constituents and Constants of Human 
Fluids and Tissues," Moscow, 1971, pp 26-27. 


"Energy and Protein Requirements," Moscow, 1974, pp 49-55. 


Popov, I. G. and Latskevich, A. A., KOSMICHESKAYA BIOL., No 2, 1982, 
pp 14-18. 


99 











UDC: 629.78:574,685:595.772-161 


OPTIMIZATION OF DEVELOPMENT OF HOUSEFLY LARVAF FOR UTILIZATION OF ORGANIC 
WASTE IN BIOLOGICAL LIFE=SUPPORT SYSTEMS FOR MAN 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 17, 
No 4, Jul-Aug 83 (manuscript received 2 Aug 82) pp 68-71 


[Article by V. V. Nosov and Ye. G. Golubeva] 


[English abstract from source] The development of Musca 
domestica L. larvae as utilizers of organic wastes in the bio- 
logical life support system was investigated by methods of 
mathematical planning. The optimization of the process under 
study is based on the reduction to the canonical form of re- 
gression models set by second order polynomials. This approach 
was tested when determining optimal conditions for larval 
development and substrate utilization with respect to 5 factors. 
On the basis of optimization results the following parameters 
were selected to ensure effective utilization of the substrate 
by larvae: the amount of substrate--150 g, its height--2.0 cm, 
temperature--34-35°, humidity--77%, larval densitv--10 larvae 
per g wet substrate. 


[Text] The prospects of continued space exploration imply that biological 
life-support systems (BLSS) for man will be created [1]. Utilization and 
return into the cycle of matter of such organic waste as human and animal 
excrements present considerably difficulties in the mineralization part 

of BLSS. 


[t is possible to use insects for utilization of waste, for example, the 
Muscal domestica L. housefly, for which human and animal excreta are the 
only substrates for development. At the present time, some preliminary 
data have already been obtained on utilization by housefly larvae of some 
of the organic waste in BLSS [2]. 


Larval development depends significantly on a number of ambient factors [3]; 
for this reason, it is necessary to find the combination of such factors 
that would be optimum for effective utilization of waste by housefly larvae. 


Our objective here was to search for optimum cond'‘tions for development of 
housefly larvae and their decomposition of the o:vganic matter of the substrate. 


100 











Methods 


[In order to solve the given problem, we used the method of mathematical 
planning. 


We selected a regression model, given in the form of a second-order polynomial, 
to describe the area of experimentation in question: 


n n 
y =@,- Dd arr - s AjeXjXp, (1) 
hel J], al 


A 
“- 


where 209, Gp, Zi are estimates of coefficients of regression; <:, <, are 
normalized values of factors X; and X1,z, respectively. 


The normalized values were linked to natural ones using the following 
formula: 


¥y == (44 — X50) 44, 


where X-, X;, is the arbitrary value of factor X,; and its value on the 
basic level in natural scale; A; is the range of variation of factor Kze 
Let 2 = (20, Ar, cers Dong 212» 214s cers ; yy ails eeeys i be the 
vector of estimates of coefficients of regres.ion (the symbol "T" refers 
to the transposition sign). Then, using the least squares method, we 


shall have [4]: 


a — (FYF)-1F TY. (2) 


where F is the matrix of independent variables and Y is the matrix of cases. 


By means of orthogonal transformation of coordinates and transformation of 
the parallel transfer type [5, 6], regression equation (1) can be reduced to 
the following canonical form: 


n 
Y= Shy +e (3) 
joi 
where A*; are the eigen values of symmetrical matrix B = ||b-,p| (bsp = bre = 
0. Asp for 46 v = he Ze eeeg Vie JF b os = As for all J = ls Ze eng nS 


Je ” 


C is a constant. 


The connection between old coordinates x = (27), %2, «++, ZT) and new 
coordinates 2 = (255 Boy sees ia? is made by means of the following 
relations: 


x == Sz 7, (4) 


where S is a matrix whose columns are orthonormalized eigen vectors of 
matrix B; z'°) is a fixed point, which is called the start of the coordinates. 


101 





Table l, Coordinates aS. i 49 » ees “2° are the 
Conditions for coding factors and solution for the following system of 
range of their variation in study linear equations [5]: 
of effect of environmental factors 
on development of housefly larvae 3 
ws Ih? 05d, 0, pel, 2 1 (5) 





ss jw! 


FACTOR CODING 
CONDIT! Ons 


Taking into consideration the condi- 


t) 
2. 
1) 
we | 
j 











FACTOR 2, | , 
ru izwe| w 8 tions in (5) the formula for deter- 
lan = 4 | a mining constant C in equation (3) will 
4 = a= |rac|e - have the following ance: 
$$ a ie following appearance: 
G | 265 | % | 325 A) 
cm | . 4 6 - n 
70 76 4 fy; \’ (0) 
-— - 19 | 2% | 37 y Cm & ay 2g + Gp. (6) 
L/G + | & 2) 4 _ 





The above-descrbed scheme for reducing 
second-order polynomial regression 
models to a canonical form will be 
used as the basis for optimization of the process under study. 


On the basis of data in the literature and previous experiments [2, 3, 7], we 
selected the following factors: X;--quantity of substrate (in g); X2--height 
of substrate layer (in cm); X3;--moisture of substrate (%); X,--ambient tem- 
perature (°C); Xs--density of larvae on substrate (number of larvae per 

gram wet substrate). Table 1 lists the conditions for coding factors and 
range of their variation. The effect of these factors on larval development 
and degree of utilization of substrate was assessed on the basis of the 
following parameters: Y,--quantity of organic matter of the substrate decom- 
posed by larvae during development (7%); {,--pupa biomass (g); { ;--duration of 
development to pupa stage (days); Y,--preimago mortality (before pupa stage) 
(%). The larvae developed in human excreta in polystyrene jars. 


We chose a second-order central composition plan with 2°! type kernel [4] 
ind generating correlation rs = £u4%3%2%,;. We repeated all of the experiments 
in the plan twice. 


Results and Discussion 


After processing the experimental data using formula (1) and discarding 
irrelevant coefficients, we obtained the following regression equations: 


Y 28,41 -+-2,76x, +- 4,84x, —3,31x,x, ~ 
- | 73x a — 2, 25x i*4 +- ie. (3x 1*5 —a. '_ : 
++ 4,43x? +. 5,663 —4,59x2 —7,92x? (7) 
VY, = 4,664+2,40x, —0,44x, —0,63x, ~ 0,64x,— (8) 
— 0,43x,x4 — 0,46x,x5-~- 1,32x5, 
Y , = 7,65-+0,78x, + 0,25x, -- 0,44x5 — 3,0x,— 
— 05x, ~-0,56x,x, — 0,44x Xg—0,44e xy 
~ 0,25x,x, — 0-B7e 1% -- 0, bx, — 0, DOK 9h > 
. 0) 44x 5%, ’ 0 69% 4%, 0, O4x5 — f), 71x (9) 
1 ,29x4, 


102 





4 66 4 1/X, 4,2n, 9,97 ke (10) 
+ BAe ty 4 6B, ~ B95 Ks 


After analyzing the obtained equations (7)-(10), we were able to note some 
of the patterns in effects of the tested factors in the chosen ranges of 
their varlation on the parameters studied. 


With increase in temperature there was an increase in larval mortality in 
the course of development and reduced pupal biomass, but development of lar- 
vae and, consequently, substrate processing occurred in a shorter time. 


An increase in larval density on the vubstrate led to increase in pupal 
biomass and degree of utilization of substrate by the larvae, 


With {ncrease in substrate moisture there was a decline of larval mortality 
during development, more intensive larval utilization of substrate, increase 
{n biomass of pupae; however, further increase in moisture led to the 
opposite effect. 


[In view of the described influence of factors on the parameters under study, 
{t 16 not deemed feasible to find unambiguously the conditions for larval 
development that would yield extreme values for all parameters at the same 
time, 


Let us effect optimization of each of the parameters studied using the method 
of reduction of regression equations to canonical form and then, let us 
select out of the calculated modes the one that would yield the extreme 

value for one of the parameters and values that would satisfy us for the 
other parameters. 


In view of the limited size of this article, we shall describe the calcula- 
tions for optimum value of output parameter only for Y,, and for the rest 
we shall merely give the end results. 


Thus, using formulas (3) and (4), equation (7) in canonical form will appear 
as follows: 
%, 7,172? + 3,427 — 0,3325 — 4,6724 — 


8B Oiz: + 28,73 (11) 


The connection between old and new coordinates is described by the 
following system of equations: 


—~ 0,092, — 0,23 


x, = 0,782, + 0,612, + 0,122, ~ ),0lz~— 
~0,012%,- 1), 26 


| x, = —0,592, +- 0,782, —0, 182, —0,102,— 





x —1),0Az, + 0,082, — 0,042,+-1,.00z,4 

.0,02,-0.04. ssc (12) (12) 
kg —0,202, + 0,082, +0,982z, +0,022,+ 

+ 0,0lz, — 0,3) 

Xs 0,042, + 0,072, —0,022, —0,032,+ 


1 ,00z, + 0,28. 


103 





Since we need to determine the maximum value for Rin let us assume that 
uy = 44 = 25 = O. Equation (11) will have the following appearance: 


V, = 7,172? + 3,422? + 28,73, 


The system of equations (12) will be as follows: 


x, = —0.592, + 0,782, ~ 0,23 
| x, <= 0,782, ~ 0,61z,— 0,26 

x, = —0,042, + 0,052,~- 0,04 
X,= —0,202, -- 0,082, + 0,31 

x, = —0,0Az, + 0,072, + 0,28 


The results of prior tests revealed that, with high values for density of 
larvae on the substrate, the amount of decomposed organic matter ci the 
substrate will not exceed an average of 50% [2]. Bearing this in mind, 

as well as the range of temperatures that are critical to survival of 

larvae [3], let us assume that 2 = -1.8, 22 = +1, then x7; = 1.6, x2 = 01.05, 
oy = 0.11, 2, = 0.75, xs = 0.42 


When making the test at this point, we could expect close to 50% substrate 
processing, which exceeds the maximum obtained from running 27 tests. 


Analogously, we can obtain the coordinates of points that yield extreme 
values for the rest of the parameters, namely, 


for Y2 xj==3,1; xg—=—1,0; x:=0; x,=0,89; 
X,==-+1; for Y; x;==—2,18; x2—=—0,22: 
X3== —0,96; x,=0,77; x; =——0,01; for 
Y, x,;=1.07; x,—=—0,08; x,——0,25; 
1,= —0,8: X,=—1,8. 


The modes calculated from the results of optimization of the process of 
larval development and their utilization of substrate are listed in Table 2. 


In analyzing the obtained modes, it should be noted first of all that the 
values of parameters Y, (amount of substrate organic matter decomposed by 
larvae during development) in mode 1, Y, (pupal biomass) in mode 10, Y; 
(mortality of larvae during development) and Y, in mode 7 have no physical 
meaning, which is related to the fact that factors X, (modes 7 and 10) and 
Xs (mode 1) exceed the range of their variation. For this reason, using 
the above modes is unwarranted. 


In modes 2 and 3, there is insignificant utilization of substrate by the 
larvae (Y,;), and since we are governed primarily by maximum possible sub- 
strate utilization in selecting the mode, because of the problem being 
solved in the BLSS with use of housefly larvae, these modes must be 
deemed ineffective. 


Under the conditions of mode 11 there is little biomass, and for this 
reason the mode is also ineffective. 


104 


te 





lable Ze Results of optimization Of proce \s OO] deve lor nent if larvae 
and their uttilizatlon of substrate 


COORDINATES OF POINT | 
MOoOnr ; Y | Y, | VY « | y 
A ‘y ‘y , ‘, | 
j | 
| () OF f) 4 4 } ‘ | , ’ 
() (ym () vs, (4 13 40) -. | te ft 
; fy ) ()K ) ‘) x 10 ln i099 12,4 5 
| 5 Wh) 75 " ) Q7 | a f ’ 
me () |] () 7% () 49 14 | 4 } if, 
1, fy | | O7% (1) 42 15.4 6.77 / 4 fot 
i 0 () 4g mi | 4" 4 1}.19 | pO 44 9 4 
2 ) 0) “9 1,9 1 197 B40) ih 
/ | 1.0 | f () 0) () AG 1 fj 11.4 1 OW 740 74.9 
) 2,14 22 0) 96 ( / 0] 4.5 1 04 4,40 HAL 
1,5 0,22 0.96 077 | 00) | 29 | OS | 1,0 | O45 
| | | | | | 


Note: Optimum modes (1, 4, / and 10) are given for each parameter and 
corresponding values for the other parameters. Modes 2, 3, 6, 8, 9 
and 11 were derived from optimum ones by varying the values of 
factors exceeding the experimentation range, s0 that they would 
approximate borderline value, 


Modes 8 and 9, as well as 4-6, provide for more utilization of substrate (Y,) 
than was obtained in each of the 27 tests. However, while there were close 
values for biomass (Y7) and diration of development (Y;), larval mortality 
(Y,) in modes 8 and 9 was almost 207% higher than in modes 4-6, and for this 
reason modes & and 9Y are unsuitable, 


Of the other modes, let us take mode 4 as the optimum for solving the set 
problem, since it provides for maximum utilization of substrate and close 
to maximum (obtained in executiug the plan for the experiment) biomass, 
as well as satisfactory development time and survival. 


Thus, as a result of analysis of the obtained modes as it applies to solving 
the formulated problem, we arrive at the conclusion that we can recommend 
mode 4 conditions for development of larvae (150 g substrate, 2 cm height 

of substrate layer, 7/77 substrate moisture, 34-35°C temperature, density 

of larvae on substrate--10 larvae/g wet substrate). 


The results of an experiment performed at this point exceed estimated 
data by 15%, which is permissible in a biological experiment [4]. 


BIBLIOGRAPHY 


l, Shepelev, Ye. Ya., in "Osnovy kosmicheskoy biologii 1 medicsiny" 
[Fundamentals of Space Blology and Medicine], !foscow, Vol 3, 19/5, 
pp 277-316. 


2. Golubeva, Ye. G. and Yerofeyeva, T. V., KOSMICHESKAYA BIOL., No 6, 1981, 
pp 54-57. 


LO5 








The parameters of desorption properties 
of some of the agents mentioned above 
are listed in the Table, which shows 
that the time of removal] of sulfur-con- 
taining agents from the Pt electrode 
is directly related to the chemistry of 
ij tne agent and potential. It was also 
noted that complete desorption of 
aaare the above agents occurs within a certain 
range of potential, below which there is 
no desorption. For example, for AET 
complete desorption is absent at a 
: . potential of less than +0.4 V; for L- 
? cystine, reduced glutatione, cystaphos 
and 2-AETSA it is absent at less than 
+0.3 V. 


“> « 
oO», 


MAMmw% 


fod 
* 


Figure 2. 
Changes in magnitude of current 
surges in different ranges of 
potential with constant concentra- 
tion of radioprotective agents 
X-axis, potential (V); y-axis, 
current (uA) with application of 
negative (7,) and positive (7,4) 
pulses on electrode. Explanation 
is given in the text. 


Thus, considering the chemical structure 
of the agents, it can be concluded that 
those containing the functional groups 
~NH2-SO3H and -COOH cannot be absorbed 
on the surface of a smooth Pt electrode 
in saline. At the same time, agents 
containing sulfur in the groups -SH, 
-SPO3;H2 and -SS0O3;H, as well as sulfur 

in the form of a disulfide bridge and 
bivalent sulfur, are adsorbed well on this electrode. Complete desorption of 
these agents from the electrode is possible only within specific ranges of 
potential. We discussed above the results of in vitro adsorption of the 
agents on an electrode. Are the adsorption properties of sulfur-containing 
radioprotective agents manifested when the ACA method is used on the 
organismic level? 


Parameters of desorption properties of sulfur-containing radioprotective 
agents in saline 














| | Purification time with appli- 
| | cation of potential on the 
Agent | Concentration, | 
| 210-2 ¥ | electrode, V 
| I +0.6 ms i +0.4 +0.3 
—— + ' , 
AET | 0.261 | 811 | 2783 | None 
L-cysteine | 0.82 | 541 | 181 | 3042 
Reduced glutathione | 0.65 | 3+1 | 5+1 | 12+1.5 
Cystaphos | 1.1 | 2 | 4+] | 9+1 
2-AETSA | 0.66 | 1 | 2e1 | 341 
i 





Figure 3 illustrates the changes in current surges in the presence of acute 
anoxia (curve 2) followed by intraperitoneal injection to rats of 60 mg/kg 
serotonine creatinine sulfate (curve 3), 250 mg/kg AET (curve 4) and 405 mg/kg 
MEA (curve 5). At the time of anoxia (curve 2), there was a reduction of 


120 








Surging current by a value corresponding to virtually total absence of oxygen 
in tissues. When the animals were changed to air breathing, surging current 
reverted to the initial level (curve 1) in view of recovery of normal partial 
oxygen tension in tissues. Thirty min after anoxia, injection of radioprotec- 
tive agents lowered appreciably the current surges, mainly due to adsorption 
of sulfur-containing radioprotectors (curves 4 and 5) and partial decrease in 
sensitivity of Pt electrode to oxygen. The latter was confirmed by the re- 
sults of experiments involving creation of additional acute anoxia against 

the background of radioprotective agents in the body. In this case (dotted 
parts of curves 4 and 5), there was some statistically unreliable decrease 

in current surges, which was less marked than under anoxic conditions without 
radioprotective agents (curve 2). Unlike the sulfur-containing radioprotective 
agents, those containing no sulfur (for example, serotonine creatinine sulfate) 
did not present adsorptivity (curve 3), since the decline of surging current 
under the effect ofthis agent corresponded entirely to the decline in 
current observed with acute anoxia, indicating that there was only an oxygen 
eftect. This is also confirmed by the ::uct that additional anoxia virtually 
failed to elicit a decline of current surges. 














' 100 ¢ if 
ae 4} Ti ) 
| YW 0% ¢j 
40) \ 
16+ 
i727 \ ° ‘| = 
b Vk F a 
08+ .'y 
| —% * 95 
06) ; 
‘ 
——o 0 530 w 
Figure 4, 
Figure 3. Change in surging current with nega- 
Change in surging current with applica- tive pulse to electrode when giving 
tion of negative pulse on electrode in animals different radioprotectors. 
the presence of anoxia (+), after its X-axis, time (h); y-axis, magnitude 
elimination (*) and subsequent adminis- of surging current (7%) 
tration of radioprotective agents 1) taurine 
X-axis, time of measurement (min); 2) reduced glutathione 
y-axis, current (vA). Curves are 3) 2=-AETSA 
explained in the text. 4,5) AET (50 and 150 mg, respectively, 


intraperitoneal injection) 


Thus, the results of this experiment are indicative of presence of adsorption 
on the electrode of sulfur-containing radioprotective agents, as well as the 
fact that the ACA method is not adequate for measuring 0» level in tissues 
when animals are given radioprotective agents. 


In the next series of experiments, we examined the distinctions of dissemina- 
tion in the body of radioprotective agents, on the basis of their adsorption 


121 








properties. Figure 1 illustrates the level of surging current with applica- 
tion of negative pulse on the Pt electrode, which characterizes the distribu- 
tion of various radioprotective agents in mice and rats. Mice were given 
intraperitoneal injections of 250 mg/kg taurine and 350 mg/kg 2-AETSA. The 
Pt clectrode was in the femoral muscle. Rats were given intraperitoneal in- 
jections of 400 mg/kg reduced glutathione, 50 and 150 mg/kg A£T (with the 
electrode in the femoral muscle) and hypodermic injections of 50 and 150 mg/kg 
AET (with the electrode in the spleen). It was established that the sulfur- 
containing agents differed substantially from one another in rate of distribu- 


tion in the body. Reduced glutathione spreads the fasted, followed by AET and, 


finally, 2-AETSA. Taurine did not affect the level of current surges, just 
like in the experiments in vitro (see Figure 2), which is indicative of the 
fact that it has no adsorption properties. 


Thus, the ACA method permits evaluation of the rate of distribution of sulfur- 
containing radioprotective agents in the body. 


The data we obtained from these studies can be used to investigate the 
kinetics of distribution of sulfur-containing agents in different animal 
specles, as well as to determine the time parameters of modified radio- 
resistance by means of radioprotective agents, evaluation of efficacy of 
radioprotective effects of sulfur-containing agents according to their ad- 
sorption on the electrode. Moreover, these data may be useful in explaining 
the nature of the decline of redox potential in animal tissues after adminis- 
tration of sulfur-containing radioprotective agents. 


BIBLIOGRAPHY 


l. Vorob'yev, Ye. I., Yefimov, V. I. and Karsanova, S. K., KOSMICHESKAYA 
BIOL., No 1, 1982, pp 4-12. 


2. Saksonov, P. P., Antipov, V. V. and Davydov, B. I., "Problems of Space 
Biology," Moscow, Vol 9, 1968. 


3. Skobets, Ye. M., in “Polyarograficheskoye opredeleniye kisloroda v 
biologicheskikh ob"yektakh" [Polarographic Determination of Oxygen in 
Biological Objects], Kiev, 1968, pp 7-22. 

4. Kazarinov, V. Ye., ELEKTROKHIMIYA, Vol 8, No 3, 1972, pp 393-395. 


5. Budnikov, G. K., "Principles and Use of Voltampere Oscillographic 
Polarography," Kazan, 1975, pp 20-158. 


6. Zaytsev, G. N., “Methods for Biometric Calculations," Moscow, 1973, p 43. 


122 





BRIEF REPORTS 
UDC: 629.78:612.1.017,2 
EFFECT OF PHENIBUT ON ORTHOSTATIC STABILITY 


Moscow KOSMICHESKAYA BIOLOGIYA i AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 15 Jan 82) pp 81-82 


[Article by E. B. Petrova and N. Ye. Panferova] 


[Text] Pharmacological agents, in particular, tranquilizers, derivatives of 
-aminobutyric acid (GABA) [1-3], are gaining increasing use for the correc- 
tion of an operator's functional state when controlling complex technological 
systems, including spacecraft. It is known that GABA derivatives maintain 

autonomic equilibrium, exerting a presynaptic and postsynaptic inhibitor 
effect on adrenergic and adrenohypophyseal systems actively involved in 
regulating cardiovascular function [4]. Since weightlessness during a 
spaceflight alters primarily the cardiovascular system, it is necessary 

to be familiar with the effects of GABA derivatives during a spaceflight, 
which imposes greater demands on the cardiovascular system. 


Our objective here was to test the effect of phenibut, a GABA derivative, on 
adaptability of the cardiovascular system. For this purpose, we tested the 
effect of this agent on man's orthostatic stability. 


Methods 


This study was conducted on 12 essentially healthy men 20 to 45 years of age. 
The subjects were divided into two groups. The first group was unrestricted 
as to motor activity and the second group was submitted to antiorthostatic 
[head-down] hypokinesia (AOH) at an angle of -12° for 4 h. A passive 5-min 
orthostatic test was performed twice, before intake of the agent and during 
the period of its action. The agents were taken once a day in various 
combinations: 0.5 phenibut, 0.5 phenibut + 0.01 ephedrine, 0.5 phenibut + 
0.01 phenamine, after the first orthostatic test. We used placebo as a 
control. During the orthostatic test, we recorded the EKG in the D-S lead 
and measured blood pressure (BP) in the background period, on the lst and 5th 
min of the orthostatic test. 


Results and Discussion 


The results of this study revealed that the change from horizontal to erect 
position elicited a reliable increase in heart rate (HR) in the first group 
of subjects, by 15-19/min in the lst min and 20-23/min in the 5th. BP did 

not change. 


123 








Table 1. Change in pulse rate during orthostatic test against the background 


of pharmacological agents 











AGENT . “TIME OF BACK- ORTHOBTATIC 
TEST GROUND IrirnsT MIN|IF IF TH MIN 
PLACEBO (| UNRESTRICTED BEFORE INTAKE way 
sere Reran'wnnane™ | (203s | ciseet | Mest 
" “am 
PLACEBO (AOH) er ie 63,743,8 | 75,344,8 | 85,9+6,1 
AFTER 58,1+2,9 78,143,0 84,2+3,5 
PHENI@UT ( AOH) BEFORE : 59,545,3 | 82,0+3,4 | 85,8+4,1 
AFTER 64,5+4,8 77,0+5,8 $2,0+6,8 
PHENIGUT + EPHEDRINE perore " 62,043,6 | 76,2+6,6 80,8+4,5 
(UNRESTRICTED ACTIVITY) |AFTER  '! 65,347,2 | 89,546,3 | 88,7+2,5 
PHENIBUT + EPHEDRINE Berorne " 62,84+6,0 | 80,347,0 | 77,0+10,0 
( Aon) AFTER " 61,2+2,9 79,5+8,0 89,0+6,5 
PHENIBUT + PHENAMINE Beronsc " 59,5+5,7 | 79,845,5 | 80,8+5,1 
(UNRESTRICTED activity) |ArTEeR  " 69,5+5,7 | 92,0+2,0 | 97,0+2,0 

















Here and in Table 2, the results obtained in the lst and 5th min 
differ reliably from background data with P<0.05. 


Note: 


In the second group of subjects, the pulse rate changed on the average 
within the same range as in the first group: by 12-20/min in the lst min and 
by 22-26/min in the 5th min. 
In the group that took phenibut, HR increased similarly to the pulse 


BP rose somewhat (by 4-9 mm Hg; Tables 1 and 2). 


changes with intake of placebo prior to intake of that agent: by 23/min in the 


lst min, 26/min in the 5th. 
less increment of HR: by 13/min in the lst min and by 16/min in the 5th. BP 
did not change appreciably (see Table 2). 


In the case of combined intake of phenibut and ephedrine by the first group 
of subjects, pulse increased by 12/min in the lst min and 7/min in the 5th 
min. Systolic BP rose by 8 mm Hg in the lst min and diastolic pressure 
increased by 9 mm Hg in the 5th min. 


The change from horizontal to erect position after being in head-down 
position, after the combined intake of phenibut and ephedrine, elicited 
an increase of 20/min of HR in the lst min and by 28/min in the 5th min; 
systolic BP rose by 5-10 mm Hg and diastolic by 15-20 mm Hg. 


Against the background of phenibut combined with phenamine, HR increased by 
24/min in the lst min and 28/min in the 5th min in subjects of the first 
group. Systolic BP rose by 14 mm Hg in the lst min, while diastolic BP 

did not change. 


Thus, the results of these studies revealed that HR parameters diminished 
in comparison to the background and intake of placebo during the 5-min 
orthostatic test after intake of phenibut in subjects who had spent 4 h in 
antiorthostatic position. 


Against the background of phenibut combined with ephedrine, in subjects 
whose motor activity was unrestricted, HR increased, but BP did not change. 


124 





After intake of the agent, there was considerably 


After 4 h in antiorthostatic position, we observed a more distinct increase 
in both HR and BP, Similar changes, but more marked, were demonstrated 
after use of phenibut combined with phenamine. 
































Table 2. Changes in BP during orthostatic test against the background 
of pharmacological agents 
pack. _ORTHOSTATIC TEST. 
AGENT TIME OF TEST BP GROUND |rinst mini FIFTH MIN 
PLACEBO BEFORE INTAKE! S 112+-5,9 106-+3,7 112+3,0 |: 
( UNRESTRICTED * D 72+4,2 7741,8 a+ 2,5 
acTivitTyv) AFTER s 120+ 3,6 1134-5,4 112+3,0 
D 722:3,5 73+1,8 76+1,9 
naneee BEFORE 7 s 113-46,1 118+-2,8 121+4,8 
UNRESTRICTED D 71+2,6 86+ 2,2 83+ 4,5 
ACTIVITY) AFTER . Ss 1292+5,8 122-+ 6,1 122+4,4 
D 79+ 3,1 79+4,] 79+3,8 
PHENI@UT ( AOM) BEFORE " Ss 127+ 10 122+ 10 115+6,1 
D 85+ 8,3 85+ 5,0 80+ 2,9 
ih) = Vs = es 
AFTER Ss 120+ 13 115+ 13 117+10 
D 72+5,0 85+ 8,3 82+ 5,0 
PHENIS@UT + EPHEDRINE | BEroRE ” Ss 117+5,8 123-+-6,2 118+6,2 
( UNRESTRICTED ~ D 74+ 1,8 81+1,7 85+ 5,0 
ACTIVITY) AFTER Ss 118+5,9 116+6,7 117+5,¢ 
D 74+4,1 79+3,8 77+5,5 
PHENI®BUT + EPHEDRINE | BEroRE 8 Ss 110+4,1 108+ 2,2 103+ 1,9 
(AOH) " D 70+3,9 72+3,2 72+1,6 
AMTER S 116+6,3 112+7,2 113-5,7 
D 82+2,8 87+ 2,4 80+4,2 
PHENIBUT + PHENAMINE | BEFORE " Ss 112+5,0 102+ 4,3 102+4,3 
( UNRESTRICTED - D 72+ 1,0 72+2,0 80+ 2,5 
activity) AFTER Ss 127+ 10 117+4,3 115+ 13 
D 77+4,3 72+ 4,3 82+7,1 
Key: S) systolic D) diastolic 


On the basis of the foregoing, it can be concluded that phenibut improves 
somewhat the functional state of the cardiovascular system during orthostatic 
tests following antiorthostatic position. The combination of phenibut and 
ephedrine, or phenibut and phenamine under the same conditions had an adverse 
effect on the cardiovascular system. The results of our studies must be 
taken into consideration when working out recommendations for use of the 
above-mentioned pharmacological agents during spaceflights. 


BIBLIOGRAPHY 


1. Shashkov, V. S. and Sabayev, V. V., KOSMICHESKAYA BIOL., No 5, 1980, pp 10-18. 
2. Vasil'yev, P. V. and Glod, G. D., Ibid, No 3, 1977, pp 3-9. 


3. Belay, V. Ye., Vasil'yev, P. V. and Glod,G. D., in "Aviakosmicheskaya 
meditsina" [Aerospace Medicine], Moscow, Vol 3, 1971, pp 118-129. 


4. Meyerson, F. Z., “Adaptation, Stress and Preventive Measures," Moscow, 
1981, pp 200-215. 


125 











v 


UDC: 629.78:612.441.018-08 
RAT THYROID HORMONES FOLLOWING FLIGHT ABOARD COSMOS-936 BIOSATELLITE 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 22 Jun 82) pp 83-84 


[Article by J. Knopp, L. Macho, R. A. Tigranyan, N. F.Kalita and V. Strbak 
(CSSR and USSR) | 


[Text] Histological studies of the rat thyroid after long-tern spaceflights 
revealed that there were some morphological signs of diminished function of 
this gland (reduction in volum of thyrocyte nuclei, shortening of epithelium, 
consolidation of colloid), as well as decrease in number and volume of C cell 
nuclei 5-12 h after landing. These changes were not present 25 days after 

the flight [1]. It was found that thyroxine (T,,) concentration of cosmonauts’ 
blood plasma was increased on the concluding day of 13-day missions aboard 
Apollo, but 1 day after the flight there was complete normalization of T, 
level [2]. In the authors’ opinion, these findings are indicative more of 
increased thyroid activity than change in blood plasma protein content 

during the flight, descent and landing, since this was associated with a 
decline of blood serum cholesterol level. Analogous results were obtained 

for cosmonauts on the Skylab orbital station, in whom some decrease in 

blood plasma triiodothyronine (T,;) concentration was also demonstrated after 
28-, 56- and 84day missions, as well as elevation of thyrotropic hormone 
(TTH) level in 5 out of 9 cosmonauts [3]. The authors believe that the in- 
crease in T, concentration is a consequence of heightened thyroid activity, 
while the decrease in T; content is the result of either diminished release 
of T3; or slow transformation of T, into T; in nonthyroid tissues. 


Our objective here was to investigate processes of formation of iodotyrosines 
and thyronines in the thyroid, as well as levels of T,, T3,;and TTH in rat 
blood plasma after a flight aboard Cosmos-936 biosatellite. 


Methods 
We conducted these studies on male Wistar-SP! ats (Bratislava, CSSR), which 
had been flown in space for 18.5 days aboar: smos-936 biosatellite. A 


description of experimental conditions is furnished in the article by Ye. A. 
Il'in et al. [4]. 


We isolated the thyroid immediately after decapitating the rats; it was 
immediately frozed in liquid nitrogen and transported in dry ice to the 


126 





laboratory for subsequent analysis. From each thyroid we prepared a homo- 
genate in 0.25 mi tris-buffer (0.04 mol/2, pH 8.4) with addition of 

Tapazole [methimazole] (0.001 mol/2); the specimens were incubated with 

the enzyme, pronase, for 16 h at 37°C, after which the hydrolysate (20 ,2) 
was applied to Whatman No 3 chromatography paper. We separated the iodinated 
amino acids by ascending chromatography on paper in a system of butanol, 
ethanol and 0.5 N ammonia (5:1:2), adding at the same time to each sample 
standard diifodotyrosine (DIT), monoiodotyrosine (MIT), T, and T,; we 

assayed iodine in some segments of the chromatograms and caculated the per- 
centage of iodinated constituents. The radioimmune analysis method was used 
to assay blood plasma TTH, T, and T,. 


Results and Discussion 


Determination of percentages of iodinated constituents of rat thyroid tissue 
revealed the following (Figure 1). DIT and MIT rose significantly in rats 

of the synchronous group that were submitted to centrifuging. T, and T, con- 
tent of the thyroid did not change in 
any of the rat groups examined. The 
parameter of intensity of processes of 
hormone production (i.e., ratio of iodo- 
tyrosines to iodothyronines) rose in 
all groups, particularly in synchronous 
control animals, in which this ratio 
was almost 6 times greater than in the 
vivarium control; these data were 
indicative of decrease in hormone- 
producing processes. 


«00! «0.02 
p<0.0! 
o<002 





129656123456 129656 129458 129456 Immediately after landing, T, in blood 
DIT MIT I ‘6 5 plasma of rats submitted to inflight 
Figure 1. centrifuging was elevated, as compared 


to both the vivarium control and 

flight rats that were in weightlessness; 
25 days after landing there was no 
longer any difference whatsoever 
between levels in animals of the tested 
groups (Figure 2). 


Percentage of iodinated amino acids 
in rat thyroid tissue 

1) shoft-arm centrifuge 

2) flight 

3) vivarium control 

4) synchronous experiment 

5) syncrhonous experiment + 

centrifuge 

6) flight + centrifuge 
Results of testing 5 animals are 
given. 


T3 content of blood plasma was virtually 
the same in all tested groups of rats, 
with the exception of cases where it 

was elevated (as compared to other 
groups) in the synchronous control 

group (see Figure 2). 


TTH content of blood plasma immediately after flight in animals who experi- 
enced weightlessness was significantly diminished, as compared to rats 
submitted to centrifuging during the flight and control groups of rats; 
plasma TTH level in flight animals did not differ from the control 25 days 
after landing (Figure 3). 


127 


“4 b 

































































Tavs 
26 days 
Postflight 
Figure 2, 
T; (mmol/2; a) and Ty (umol/2; b) 
content of rat blood plasma. 
Asterisk shows reliability (P<0.01) 
in relation to parameters for the 


other groups. Here and in Figure 3: 


1) vivarium control 

2) flight 

3) flight + centrifuge 

4) synchronous experiment 

5) synchronous experiment + 
centrifuge 

6) short-arm centrifuge 





25 days 
Postflight 


Figure 3. 
TTH content (yunits/m2) in rat blood 
plasma. Asterisk shows reliability 
(P<0.01) in relation to parameters 
for vivarium control and flight animals 
in centrifuge 


Our findings indicate that no appreciable 
changes in thyroid function occurred 
during a long-term spaceflight. In 
spite of the fact that we demonstrated 
an increase in blood plasma Ty, and T;3 
concentration, one cannot conclude 
from the results that elevation of 
hormone levels occurred due to in- 
crease in thyroid function. It is 

most probable that elevation of 
thyroid hormone levels occurred either 
due to their diminished utilization or 
diminished activity of deiodinating 
enzymes. Intake of iodine during the 


flight is also rather important. The feed consumed by rats during the 
flight contained about 100 ug iodine/day, and this amount can probably 


alter synthesis of T, and T;. 


BIBLIOGRAPHY 


l. Plakhuta-Plakutina, G. I., KOSMICHESKAYA BIOL., No 3, 1980, pp 29-33. 


2. Sheinfeld, M., Leach, C. S. et al., AVIAT. SPACE ENVIRONM. MED., Vol 46, 


1975, pp 47-49, 


3. Leach, C. S., Johnson, P. C. et al., Ibid, Vol 48, 1977, pp 595-597. 


4. Il'in, Ye. A., Korol'kov, V. I. et al., KOSMICHESKAYA BIOL., No 6, 1979, 


pp 18-22. 


128 








UDC: 629.78:612.822.1.014.22.577.175.52 


EFFECT OF LONG-TERM SPACEFLIGHT ON CATECHOLAMINE CONTENT OF ISOLATED NUCLEI 
OF RAT BRAIN 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA !.ZDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 28 Oct 82) pp 84-86 


[Article by R. Kvetnansky, R. A. Tigranyan and J. Culman (CSSR and USSR) ] 


[Text] A prolonged spaceflight is associated with numerous factors that 
affect neuroendocrine reactions. For this reason, it is quite justified to 
assume that changes occur in catecholamine (CA) metabolism in the brain 
under the influence of spaceflight factors. Considering current knowledge 
about the numerous functions of different parts of the brain, investigation 
of CA metabolism in the whole stem and hypothalamus is less informative and 
satisfactory. In recent years, good results have been obtained by the 
method of isolation of individual nuclei from different brain structures. 
The studies of CA metabolism in the rat hypothalamus, which were pursued 

in an experiment aboard Cosmos-1129 biosatellite, revealed that only some 
parts of the hypothalamus reacted in the form of change (drop) in CA level 
after the spaceflight, mainly the nucleus arcudtus, nucleus periventricularis 
and eminentia medialis [2]. 


We report here on a study of epinephrine (EP), norepinephrine (NE) and dopamine 
(DA) concentrations in isolated nuclei of the brain stem, limbic system, as 
well as cerebellum of rats after a long-term spacefl -ht aboard Cosmos-1129. 

It should be noted that such studies of the animal brain following spaceflights 
had not been conducted before. 


Methods 


We conducted our studies on male Wistar rats (Bratislava, CSSR) who had been 
flown in space for 18.5 days aboard Cosmos-1129 biosatellite. The animals 
were submitted to euthanasia 6-8 h after landing and on the 6th postflight 
day, and some of the animals examined on the 6th postflight day were sub- 
mitted to immobilization stress 5 times (150 min daily); the animals in the 
control and synchronous groups were also submitted to repeated immobilization 
stress. 


We prepared sections, 300 nm in thickness from the frozen rat brain in a 
cryostat at a temperature of -15°C; the nuclei were isolated from the sec- 
tions under a microscope using the method described in [1]. 


129 






























































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We singled out four regions of the brain stem containing the bodies of some 
catecholaminergic and serotoninergic neurons that adrenergically innervate 
virtually the entire brain and cerebellum; we also singled out three regions 
{n the limbic system that are particularly involved in mechenisms of emotional] 
stress. In these nuclei, as well as the cerebellum, we assayed the concentra- 
tions of E, NE and DA by the radioenzymatic method [3]. Statistical relia- 
bility was calculated using Student's ¢ test. 


Results and Discussion 


We demonstrated relatively minor changes in CA concentration in brain stem 
nuclei of animals decapited immediately after terminating the experiment; flight 
rats presented a decrease in DA content (as compared to the vivarium control) 
and E (as compared to levels found in the synchronous experiment) in the locus 
coeruleus, whereas animals used in the synchronous experiment showed a decrcase 
(as compared to vivarium control) in concentrations of NE and DA in locus 
coeruleus and NE in area A, (Table 1). No changes were demonstrated in CA 
levels in the cerebellum and lLimbic system nuclei, with the exception of a 
reliable decline (as compared to vivarium control) of E concentration in the 
septum of animals in the synchronous experiment (Table 2). 


No changes were found in concentrations of CA in nuclei of the brain stem, 
limbic system and cerebellum 6 days after the experiment, with the exception 

of a decrease (as compared to vivarium control) in DA content of the locus 
co@ruleus in rats of the synchronous experiment, as well as decrease in DA 
concentration in flight rats (as compared to synchronous control) and increase 
in DA content in animals of the synchronous experiment (as compared to vivarium 
control) in the amygdala centralis (see Tables 1 and 2). 


After conclusion of the experiment, the rats were submitted to repeated 
immobilization. No changes in CA concentration were demonstrable in any 

o. the groups of animals in areas A; and Az, or in the cerebellum (see Tables 
l and 2). At the same time, similar findings were made in the locus coeruleus 
and nucleus raphe magnus--decrease in NE and DA concentration in vivarium 
control and synchronous experiment animals (as compared to intact control) 

and increase (only in locus coeruleus) in NE and DA content of flight animals 
submitted to repeated stress, as compared to both control groups (see Table 1). 
Nuclei of the limbic system responded to repeated stress in the following 
manner: decrease (as compared to intact control) in NE content of the amygdala 
centralis of animals in the synchronous experiment and amygdala lateralis of 
rats in all tested groups, as well as DA in the amygdala centralis and later- 
alis of flight rats, E in the septum of flight animals and those in the 
synchronous experiment; the decrease in DA concentration of the amygdala 
centralis and lateralis of flight rats was also reltable, as compared to 
parameters for the corresponding group in the synchronous experiment (see 
Table 2). 


At the present time, there are very sparse data concerning the effect of 
stress on concentration of CA in isolated nuclei of the stem and limbic 
system, as well as cerebellum. It has been demonstrated that there is a 
decrease in concentration of E in areas A; and A,and locus coeruleus following 


131 








20-min and especially 240-min immobilization [4]. According to our data [5}, 
3O- and 150-min immobilization led to decrease in NE and DA content of area A» 
and locus coeruleus. As for the effect of repeated immobilization stress, 
there is no information at the present time concerning changes in CA content 
of the brain structures examined, 


Our findings indicate that only some regions of the brain stem and limbic sys- 
tem react in the form of alteration of CA level after conclusion of a space- 
flight, chiefly the locus coeruleus, in which maximum changes had been pre- 
viously demonstrated in CA content following acute stress [4, 5]. The 
diminished levels of E and DA in locus coeruleus are convincing evidence of 
the fact that rats were under stress during the landing. It is not deemed 
possible to give an unequivocal answer to the question of whether this 
stressor was acute or chronic, in view of absence of data about changes in 

CA content of the structures examined under the effect of repeated immobiliza- 
tion stress. However, by analogy with hypothalamic nuclei [2], it can be 
assumed that acute stress, occurring at the moment of biosatellite landing, 
was the most probable cause of decline in CA concentration of locus 

coeruleus. 


BIBLIOGRAPHY 


1. Palkovits, M., BRAIN RES., Vol 59, 1973, pp 449-450. 


2. Tigranyan, R. A. and Kvetnansky, R., NEYROKHIMIYA, Vol 1, No 3, 1982, 
pp 211-220. 


3}. Kvetnmansky, R. and Tigranyan, R. A., KOSMICHESKAYA BIOL., No 1, 1982, 
Ppp 80-83. 


4, Saavedra, J. M., in "Catecholamines and Stress: Recent Advances," Eds. 
E. Usdin, RK. Kvetnansky and J. Kopin, New York, 1980, pp 37-45. 


5. Culman, J. and Kvetnansky, R., Ibid, 1982, pp 69-74. 


132 





UDC: 616.71.018,.46-02:615,835.12)-092.9 


CHROMOSOME ABERRATIONS IN BONE MARROW CELLS OF RATS SUBMITTED TO HYPERBARIC 
OXYGENATION 


Moscow KOSMICHESKAYA BIOLOGIYA IL AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/, 
No 4, Jul-Aug 83 (manuscript received 27 Apr 82) pp 87-88 


[Article by Ye. P. Gus'kov] 


[Text] The genetic sequelae of hyperbaric oxygenation (HBO) have not been 
sufficiently investigated. An attempt was made here to demonstrate in rt 
hone marrow cells the cytogenetic consequences of HBO combined with the 
anticarcinogen, sarcolysin. 


Methods 


Experiments were conducted on 75 male rats weighing 200-250 g. The animals 
were placed in a pressure chamber where, after 3-min pumping of oxygen, a 
pressure of 4 atm was maintained for 2 h. In each version of the test, we 
used at least 5 rats. Upon conclusion of this exposure, the animals were 
decapitated after 6 and 24 h, and bone marrow was flushed out of the femurs 
into centrifuge tubes with Carnoy fixative. After 3-fold elution, the cell 
suspension was applied to slides. The preparations were stained with azure 
blue dye and eosin according to Romanovskiy. We recorded chromosome aberra- 
tions at the stages of late anaphase--early telophase. In one of the 
versions, the rats were given sarcolysin at the rate of 0.002 mg/g weight 
2h before HBO, 


Results and Discussion 


The Table ‘ists data, which show that there was an increase in number of 

cells with aberrations of chromosomes to almost double the control 6 h after 

HBO, and it did not decrease for 24 h after HBO. After 6 h, there was ; 
increase in relative share of cells with fragments and by the 24th h there 

was increase in relative share of chromosome bridges. 


The Table lists the results of combined use of sarcolysin and HBO. Sarcolysin 
elicited just as many chromosome aberrations 24 h after it was administered 

as HBO; however, there was a different spectrum of induced aberrations: con- 
siderable decrease in share of fragments and increase in share of chromosome 
bridges. The combined use of the two agents elicited an additive effect, 

but half of all the aberrations consisted of fragments. 


133 





Results of cytogenetic analysis of rat bone marrow cells treated with 
HBO and HBO with sarcolysin 





-- —_— ; T 


Aberrations " 







































































Fixinc Total Ana- - 
Treatment ty ana- phases chromo- 
oe ck an frag- jchromatid some 
h phases | with ab : 
' | ments |bridges (bridges 
errations | 
HBO 
Control 24 1480 46 12 a. 6; 
HBO | 6 1120 Be | 2 42 8 
HBO { | 1760 178 46 49 | 5() 
HBO and sarcolysin 
Control 24 197 107 | 25 58 of 
HBO 6 1997 244° &3 | = 45 46 
HBO 24 1130 cs Oe? en 
Sarcolysin 24 860 115° 13 | 44 ys 
Sarcolysin + HBO 4 690 222° 114 of 4 
| 
*Pp<0.005. 
0 ; The differences between groups of 
' . - ‘ | control animals were statistically 
Bs 4 unreliable; however, the tendency 
bo | } toward more aberrations in the second 
) 030, } g control could be attributable to the 
4 : fact that the first series of experi- 
: 4 20 ' ments was conducted in January and 
- 
v the second in March, and in the latter 
& %10} } case the hormonal changes in males 
™ y ; could have been the cause of the 
~~ & 
ES ii. un - 7 , observed tendency. 
The information in the literature 
Change in spectrum of chromosome , 
concerning the cytotoxic and cyto- 
iberrations in rat bone marrow cells ee | 
“ génetic effects of HBO is extremely 
ifter HBO and sarcolysin. White ee le oe 
bere represent fremmente, hatehed contradictory [1]. Most data were 
pee P , obtained with treatment of tissue 
bars--chromatic bridges, black bars-- 

' brid cultures, whereas there is insuffi- 
~ os we a cient information about the response 
tL. IIT) oa. ’ nd 24h of tissues of intact organisms to HBO 

. ane Pave ‘ , [2]. The above-described results 
, y indicate that, in therapeutic doses, 
IV) sarcolysin, 24 h 
VY) HBO + sarcolysin, 24 h HBO is a mutagen for bone marrow 
tice , cells. The genetic aspect of HBO 





effects could be a rather substantial 


obstacle to extensive use of high oxygen pressure in clinical practice, and 
consequently it requires thorough and comprehensive investigation. In recent 
years, HBO has been used in oncological practice to enhance the therapeutic 
effect of anticarcinogens [3, 4]. It has been determined that, with the 
combined treatment of tumors with HBO and adriamycin, there is depression 


134 





of the effect of adriamycin, but If it is injected into tissue immediately 
aiter HBO, there is drastic enhancement of the anticarcinogenic eftiect of 
this agent [5]. Mustard gas combined with HBO and without it elicits the 
same effect. Sarcolysin, which contains an yperite group bound with amino 
acid, enhances by almost 2 times the effect of mutagens when used in combina- 
tion (see Table). The Figure illustrates data on incidence of different 
types of chromosome aberrations in the control and experiment. Six hours 
after HBO, there is an increase in quantity of fragments that appeared at 

the end of the S and Gy phases. By the 24th h, most aberrations are repre- 
sented by metabolic disturbances in the G,; phase. By the 24th h, sarcolysin 
also elicited chiefly chromosome bridges; however, when combined with HBO, 
the largest share of aberrations consisted of fragments. The interaction of 
the two mutagens either prevented chromosome repair processes or elicited a 
prolonged effect, as a result of which the aberrations appeared in the G, 
phase after the treatment. Thus, analysis of the spectrum of aberrations 
yields additional information about the nature of the cytogenetic effects 

of HBO on the genetic system. The submitted results may be indicative of the 
fact that the G,; phase is more sensitive to HBO than G,. This is evident 
when we compare the number of aberrations in the first and second fixations 
after termination of HBO. 


Thus, the submitted data indicate that HBO is a mutagenic factor, not only 
for microorganisms, plants and cultures of animal tissues, but for intact 
mammals. 


BIBLIOGRAPHY 
|. Haugaard, N., PHYSIOL. REV., Vol 48, 1968, pp 311-373. 


2. Krichevskaya, A. A., Lukash, A. 1. and Bronovitskaya, Z. G., “Biochemical 
Mechanisms of Oxygen Poisoning," Rostov-on-Don, 1980. 


3. Mose, J. R., ZBL. BAKT. I. ABT. ORIG., Vol A244, 1979, pp 541-545. 


4, Shuvayeve, N. I., Dar'yalova, S. L. and Vedernikova, N. V., in 
"Mezhdunarodrvy kongress po giperbaricheskoy meditsine. 7-y. Tezisy" 
(Summaries of Yapers Delivered at 7th International Congress on 
Hyperbaric Medicine], Moscow, 1981, p 139. 

5. Weller, R 
pp 310-37 


», Dirks, T. W., Lunardi, I. et al., CANCER RES., Vol 39, 1979, 
-P 


135 











UDC: 612.273.2-06:615.217.24]-08:612.111.7 


EFFECT OF LONG-TERM ADMINISTRATION OF OBSIDAN ON RAT RESISTANCE TO HYPOXIA 
AND THKOMBOCYTE AGGREGATION DURING ADAPTATION TO MODERATE ALTITUDE 
(1600 METERS) 


Moscow KOSMICHESKAYA BIOLOGIYA I AVILAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 7 Sep 82) pp 88-90 


[Article by M. A. Aliyev, V. A. Lemeshenko, A. K. Bekbolotova and 
G. K. Ryskulova] 


[Text] Adaptation of animals to moderate and high altitudes improves their 
resistance to hypoxia [1, 2]. The combination of adaptation to altitude 

and certain pharmacological agents enhances even more animal resistance [3]. 
we have been searching for drugs with antihypoxic action in the mountains 
for a long time. It is known that aggregation of thrombocytes induced 

by ADP and epinephrine is inhibited by a f-adrenoreceptor blocking agent, 
such as propranolol (obsidan, inderal). It depresses the release reaction, 
has a nonspecific effect on thrombocyte membranes, diminishing their 
adhesiveness [4]. 


Our object here was to determine the antihypoxia and antiaggregation proper- 
ties of obsidan when given once and for a long period of time under two 
different ecological conditions, in the "plains" (Frunze) and at moderate 
altitude (Issyk-Kul Lake, 1600 m). 


Methods 


We conducted our studies with 132 mongrel male rats weighing 180-200 g, which 
were divided into groups. There were 5-6 animals per group. To test 
resistance to hypoxia we used the method of determining "spare time," or 
survival time of rats at an “altitude” of 12,000 m [1]. The rate of ascent 
constituted 25 m/s, and the “spare time” was counted from the moment the 
"nlateau" at 12,000 m was reached to the second agonal inspiration. The 

rats were "brought down" alive and blood was taken 2-3 min later. We used 
the micromethod described in [5] to demonstrate thrombocyte aggregation. 
Obsidan was given intramuscularly ina dosage of 0.5 mg/kg. 


Results and Discussion 


A single injection of obsidan under "plain" conditions increased with statis- 
tical significance rat resistance to hypoxia, as compared to “moderate 


136 





altitude" (Table 1). After descend- 
ing from an "altitude" of 12,000 m, 
platelet aggregating activity did 
not change appreciably in either group 
of animals. Only the time of onset 
of aggregation and disaggregation 
diminished appreciably in rats who 
were in the "plain." No differences 
in degree of disaggregation were de- 
monstrable. In the case of long- 
term adm_nistration of obsidan, “spare 
time” increased by more than 4 times 
on the 10th day in the rats of this 
group, as compared to the data for 
"moderate altitude" animals. Their 
thrombocyte-vascular hemostasis did 
not change appreciably, whereas dis- 
aggregation diminished in the rats 
at "moderate altitude." 


Extent of 
disaggr. 
% 








min 








Platelet 
disaggreg. 


time, 








t. 


| time, min 


Platelet 


The increase in resistance to hypoxia 
in animals kept on the "plain" and 
given obsidan for 10 days was tran- 
sient, since it disappeared by the 
15th day. Thus, after giving obsidan 
for 2 weeks, there was drastic re- 
duction of "spare time” for the 
"plain" rats. Retention of moderate 
resistance to hypoxia in the animals 
at moderate altitude who were given 
obsidan was associated not only with 
moderate intensification of platelet 
aggregation, but marked increase in 
disaggregation, as compared to the 
10th day of injections. On the 20th 
day of obsidan injections, resistance 
to hypoxia was low in lowland animals, 
whereas in the “moderate altitude” 
animals it was, as before, moderate. 
There was repeated intensification 

of thrombocyte aggregation followed 
by intensive disaggregation. On the 
30th day of obsidan injections, 
resistance to hypoxia diminished in 
both groups of animals, but this was 
not associated with change in 
platelet function. 


}aqgqgrega 








Maximum 
gregat.%/aggregat. 
% 
2 
} 
Ss 
4 
24-6 
48,5+6 


ter lmin 











—_—_—— ee 





Platelet 
ia 
af 


; 
' 
i 








hy 
t. 


of 12,000 m min 
= 
+ 
+ 
+ 
+ 
t 
t 
t 
t 
+ 
+ 





Survival (s 
time) at a 











"Plain™ 
Control 
“Mod.alt.” 
Control 
"Plain" 
“Mod.alt ." 
"Plain™ 
"“Mod.alt." 
“Plain” 
"Mod.alt." 
"Plain”™ 
"“Mod.alt.” 


Here and in Table 2, the asterisk indicates reliability of difference, P<0.05. 


Conditions 





injection of obsidan to rats in the “lowlands” and during adaptation to moderate 


Change in resistance to hypoxia and platelet aggregation activity with long-term 
altitude (1600 m) 


Note 


Thus, only 10-day administration of 
obsidan was effective in enhancing 
rat resistance to hypoxia under 
ordinary conditions and in the 


l * 
Obsidan 
given 
10th day 
15th day 
20th day 
30th day 


Once 











Table 


137 








"lowlands." In the mountains (1600 m), neither single nor 10-day injections of 
this agent improved it appreciably. We compared the the results of preventive 
use of obsidan against hypoxia with those of "pure" adaptation to moderate 
altitudes (Table 2). As can be seen in Table 2, on the 10th day of administra- 
tion of obsidan, the rats’ "spare time" was one-half as long at moderate 
altitude as with “pure” adaptation. Subsequently (15th and 20th day), this 
difference was no longer demonstrable, although there was retention of moderate 
resistance to hypoxia in both groups of rats. However, on the 30th day of 
obsidan injections, there was drastic reduction of "spare time," whereas in 
rats with "pure" adaptation there remained, as before, moderate resistance to 
hypoxia. Such adaptation-induced (without use of obsidan) resistance to 
hypoxia was associated with considerable intensification of the disaggregation 
process in response to hyperaggregation of blood platelets. 


Table 2. Comparative characteristics of levels of resistance to hypoxia and 
platelet aggregation activity in rats with long-term administration 
of obsidan at moderate altitude and with "pure" adaptation to such 






































altitudes 
. . chal Platel. Start Start of| Extent of 
Way ¢ OnvS1Ganh , , 
a ot Pee oy "Spare aggreg. | Maximum of Ais- platelet 
pjyeec nS « ' ee : 
f: = time after aggreg. | aggreg. | aggreg. | disaggreg. 
pure , . ; i 
aday tation min lmin, % % min min | 5 
10th day: : 
obsidan 4,8+0,7 42,5-+4 48,545 441 10+1 39,7+6 
"pure" adaptation | 9,9+3° 48,5+7 51,147 3+0,1 6+1° Mtl 
ee opsi dan 5541 | s36e5 | sta | oer | Sat | 59,7211 
"pure" adaptation 7,3+2 46,7+5 50,35 9+0,6 7+1 72+ 12 
20th day: 
obsidan 5+! 50,94 58,7+3 ~e R~-2 72,5+8 
“pure” adaptation 4,7+3 50,44-7 57,147 2+0,5 4+0,7 63,3+ 11 
30th day: 
obsidan 19+ 1 40,37 55,7+9 3+1 6+ | 58, 8+ 6 
"pure" adaptation | 6+2 58,2+ 4° 59+ 4 1+0,4 6+2 70,7+6° 
Saino j 
fhus, prolonged blocking of 8-adrenoreceptors by obsidan in a mountain 


region ultimately causes drastic decrease in rat resistance to hypoxia, 
although this is demonstrable much later (30th day) than in the "lowlands" 
(15th day). At a moderate altitude (adaptation for 30 days), a number of 
homeostatic parameters on the’ systemic, cellular and integral levels acquire 
resistance; the parameters of the hypothalamo-hypophyseo-adrenocortical 
system (HHACS) reach the range of the “adaptive norm” [6]. Against such a 
background, the “moderate altitude" rats demonstrate increase in resistance 
to hypoxia. Hydrocortisone, when given once to rats adapted to moderate 
altitudes, prolongs by more than double the “spare time" which is already 
increased (as compared to the "plain" animals) [7]. In the same work [7], 
it was demonstrated that obsidan together with hydrocortisone increase 


138 





rat resistance to hypoxia considerably more than obsidan alone. We cannot 
fail to note that the natural means of enhancing resistance to hypoxia in 

a mountain climate does not require obsidan premedication which, by blocking 
@-adrenoreceptors, probably disrupts development of nonspecific resistance. 
lt was recently established that the acute obsidan test elicits in high- 
landers a decrease in cardiac output against a background of elevation of 
systolic pulmonary arterial pressure, build-up of pulmonary vasoconstriction 
and worsening of cerebral blood flow. This mechanism could play the leading 
role in lowering resistance to hypoxia in animals given obsidan at high 
altitudes. Hence the advantage of “pure” altitude adaptation prior to obsidan. 
Our experimental data agree with the results of other authors [1] who demon- 
strated that one can increase resistance to hypoxia in both animals and man 
by means of adaptation to alpine conditions. 


BIBLIOGRAPHY 


1. Agadzhanyan, N. A., in "Spetsial'naya i klinicheskaya fiziologiya 
gipoksicheskikh sostoyaniy" [Special and Clinical Physiology of 
Hypoxic States], Kiev, Pt 1, 1979, pp 189-194, 


2. Aliyev, M. A., “Adaptation to Mountain Climate in the Presence of 
Arterial Hypertension," Frunze, 1978. 


3. Aliyev, M. A. and Sultakeyev, R. S., in "Kirgizskiy in-t krayevoy 
meditsiny. Godichnaya nauch. sessiya. 3-ya. Materialy" [Proceedings of 
3d Annual Scientific Session of the Kirghiz Institute of Regional 
Medicine], Frunze, 1966, pp 15-19. 


4, Chernook, T. B., in "Stress i adaptatsiya" [Stress and Adaptation], 
Kishinev, 1978, p 200. 


5. Bygdeman, S. and Johnsen, O., ACTA PHYSIOL. SCAND., Vol 75, 1969, 
pp 129-138. 


6. Baluda, V. P., Chekalina, S. I., Sushkevich, G. N. et al., LAB. DELO, 
No ll, 1976, pp 653-656. 


7. Chernook, T. B., in "Stress i adaptatsiya," Kishinev, 1978, p 200. 





139 





UDC: 612.82/.83.014.426-06:612.015.31:546.15]-08 


ROLE OF CENTRAL NERVOUS SYSTEM IN CHANGING ORGAN AND TISSUE LODINE CONTENT 
DURING EXPOSURE TO VARIABLE MAGNETIC FIELD 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (manuscript received 5 Aug 82) pp 90-92 


[Article by N. V. Marsakova] 


[Text] Several researchers have noted the high sensitivity of the autonomic 
nervous system to magnetic fields (MF) [1-3]. In particular, it was demon- 
strated that the hypothalamus affects the thyroid via the hypophysis: increase 
in thyroid SH groups under the effect of exposure of the rat head to a 
variable magnetic field (VMF) [4]. 


In our previous studies [5-7], we demonstrated the compensatory effect of 

VMF with intensity of 0.11 mT and frequency of 50 Hz on parameters of protein 
and carbohydrate metabolism in rat blood serum, on levels of copper and 
iodine in organs in the case of 3-day exposure to VMF. It was also reported 
that there was activation of the thyroid with 60-day exposure to VMF of 

rats kept on their regular diet. 


We assumed that these changes occurred as a result of the direct effect of 
VMF on the CNS [central nervous system], i.e., we concurred with Yu. A. 
Kholodov [8]. In addition to the cerebral cortex, the hypothalamus is 

the part of the CNS that is the most reactive to MF; it is functionally 
connected with the anterior lobe of the hypophysis. It stimulates synthesis 
of thyrotropic hormone, which intensifies thyroid function. 


To check our hypothesis, we conducted an additional study, the purpose of 
which was to determine the role of the CNS in changing iodine content of 
organs and tissues during exposure to VMF. 


For this purpose, it was necessary to isolate the thyroid from the impulses 
traveling from the CNS, and for this we used benzohexonium, which is a 
ganglion blocking agent of n-cholinoreactive systems in ganglia cells of 
the sympathetic and parasympathetic nervous system [9]. Blocking the 
ganglia attenuates or arrests completely the flow of impulses from the CNS 
to organs that receive autonomous innervation [10]. 


140 





Methods 


We conducted the study on 80 male rats weighing 180-200 g, of which we formed 
2 groups: one was kept on the regular diet and the other on a diet deficient 
in copper, fodine and cobait. Half the animals in each group was exposed to 
VMF with intensity of 0.11 mT and frequency of 50 Hz for 3 h per day for 30 
days. Control animals were kept under identical conditions. Upon conclusion 
of the experiment, the rats were sacrificed by rapid decapitation. Total 
iodine in organs and tissues was assayed by the method proposed in [11]; we 
also recorded the weight of the thyroid. Benzohexonium was given to 24 rats 
intramuscularly, in a dosage of 30 mg/kg, 30 min before exposure to VMF, 

for the first 10 days of the experiment and, after a 10-day interval, for 
another 10 days to the end of the experiment. 


Results and Discussion 


After giving benzohexonium, total todine content of organs and tissues was 
lower in animals kept on a regular diet than in those that were not given 
this agent. Analogous changes were observed after administration of benzo- 
hexonium to animals whose diet was deficient in copper, iodine and cobalt 
(Table 1). 


fable 1. Total iodine content of rat organs and tissues (M+m) 






































|Charac- ) \Diet with copper, 
| | teristica Regular diet |iodine and cobalt 
Obrect studied | deficiency 
of expe- 
ss oriment control | MF {| control | MF _ 
Thyroid, mg% - | 48.05+0,68 | 37,6+0,98* | 36,6+0,76 | 42,58+0,97° 
. | 32,2+0,47 31,8+0,68 18,4+0,61 18,0+0,05 
Liver, Ugt 6,73+0,18 8 83+ 0,26° 4,00+0,16 5,23+-0,19° 
-- 5,450 ,32 5,27+-0,38 2,6+0,22 2,43+0,21 
Muscles, ug _ 4,7+0,13 §,28+0,19° 2,06+0,14 3,09+0,17* 
| - 3,56+0,16 3,65+0,24 1,43+0,14 1,43+0,14 
Spleen, yds -- 5,65+0,29 7,6+0,32° 3,3+0,12 4,89+0,21° 
= 3,65+0.37 | 3,65+0,21 1 ,92+0,31 1 ,93~0,17 
Heart, wUg% - 5,45=-0,29 5,944-0,32 3,03+0,17 4,12+0,24° 
+ 3,83+0,40 4,01-0,H4 2,1+0,001 2,1+0,001 
Kidneys, wg% — 5,11+0,26 7,13+0,35° |- 2,81+0,12 3,65+0,15° 
> 2,93+-0,17 3,140,001 1,76+0,21 1,77~0,21 
Urine, wGs —- 6,13+-0,14 &.64+0,27° 5,03+0,18 5,94+0,3° 
-- 3,67+0,26 3,63+0,18 2,43+0,23 2,53+0,17 
Fur, ug% 14,34+0,30 16,7+0,43* | 9,50+0,27 12,1+0,34° 
§,98+0,43 §,80+0,34 | 4,38+0,34 4,57+0,23 
| 
Key: -) without benzohexonium +) benzohexonium given *P<0.001 


The demonstrated changes coincided with previous findings [12] in a study of 
changes in iodine content of the thyroid against the background of giving 
rats hexonium methylsulfate. 


According to the views of G. P. Smirnov, the results can be interpreted as 
follows: the decrease in iodine content of the thyroid and all tested 
organs is attributable to blocking by hexonium of impulses from the CNS to 


141 








the thyroid aud inhibition of its tissue metabolism. Moreover, as believed 
by G. P. Smirnov, there is also blocking of thyrotropic function of the 
pituitary. 


fable 2. Weight of thyroid (mg) Mtm 








Regular diet | Diet with copper, 


Cnaracteristics of , , 
, | iodine and cobalt 

















experiment 4 deficiency 
— —— , control | MF control | My 
| ra ' — -—- ee 
us , ,' | 
Witnout benzonexonium | 14,72+0,09 15,5+-0,14° | 15,.56+0,18 | 14,86+0.06°° 
With benzohexonium | 13,94+0,11 14,1404 | 15,620,17 | 15,55+0,16 


” 
~ 


| 


| 











* P—0,01, oe P<0),05. 


Exposure to VMF after administration of benzohexonium did not elicit reliable 
changes in todine content of organ and tissues in either of the groups of 
rats, whereas reliable changes were demonstrable in the control. 


There was no change in weight of the thyroid under the effect of benzohexonium 
(Table 2), although G. P. Smirnov observed in his experiments a decline of 
this parameter. VMF against a background of benzohexonium did not have a 
reliable effect on thyroid weight or activity. 


Thus, blocking of impulse conduction from the CNS affected metabolic pro- 
cesses in the thyroid. VMF, which had a positive effect when used for 

30 days without this agent, elicited no changes after administration of benzo- 
hexonium. These findings indicate that the effect of VMF on the thyroid and, 
consequently, on organs and tissues is mediated through the CNS, in particular, 
through the hypothalamohypophyseal route. 


BIBLIOGRAPHY 


Kholodov, Yu. A., "Nervous System Reaction to Electromagnetic Fields," 
Moscow, 1975, p 68. 


2. Kholodov, Yu. A. and Shishlo, M. A., "Electromagnetic Fields in 
Neurophysiology," Moscow, 1979, p 83. 


3. Yakovleva, M. I., "Physiolozical Mechanisms of Effects of Electromagnetic 
Ficlds," Leningrad, 1973. 


4, Ukolova, M. A. and Kvakina, Ye. B., in "Vliyaniye magnitnykh poley na 
biologicheskiye ob"yekty" [Effects of Magnetic Fields on Biological 
Systems], Moscow, 1971, p 147. 


5. Marsakova, N. V. and Nazarenko, L. D., in "Primeneniye magnitnykh poley 


v meditsine, biologii i sel'skom khozyaystve" [Use of Magnetic Fields 
in Medicine, Biology and Agriculture], Saratov, 1978, p 48. 


142 








LO. 


ll, 


LZ. 


Marsakova, N. V., in "Magnitobiologiya i magnitoterapiya v meditsine’ 
[Magnetobiology and Magnetotherapy in Medicine], Vitebsk, 198, p 71. 


Idem, in "Adaptatsiya i ekstremal'nym usloviyam" [Adaptation to Extreme 
Conditions], Syktyvkar, 1982, p 6l. 


Kholodov, Yu. A., "The Brain in Electromagnetic Fields," Moscow, 1982, 


p 102. 


Denisenko, P. P., FARMAKOL. I TOKSIKOL., No 3, 1956, pp 9-16. 


\nichkov, S. V. and Belen'kiy, M. L., "Textbook of Pharmacology," 3d ed., 


eningrad, 1969, p 172. 


lapina, L. N., Rish, M. A. and Ben-Utyayeva, G. S., TRUDY IN-TA 
KARAKULEVODSTVA, Vol 9, 1959, p 149, 


Smirnov, G. P., PROBL. ENDOKRINOL., No 4, 1957, p 22. 











ANNIVERSARIES 


UDC: 629.78:612]:92 Parin 


VASILIY VASIL'YEVICH PARIN (ON 80TH ANNIVERSARY OF BIRTHDAY) 


Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian Vol 1/7, 
No 4, Jul-Aug 83 (signed to press 10 Jun 83) pp 93-95 


[Article by editorial board] 


[Text] The outstanding Soviet scientist, Academician Vasiliy Vasil'yevich 
Parin, is one of the founders of space biology and medicine. The talent 

and giftedness of Vasiliy Vasil'yevich were vividly manifested in this 
discipline, which emerged on the borderline of natural, medical and engineer- 
ing disciplines. He believed that it is expressly in this field that it 

was necessary to make bold use of new methods, equipment and scientific ideas. 
V. V. Parin placed everything that was new and progressive in physiology and 
medicine at the disposal of practical support of spaceflights. V. V. Parin 
saw the first cosmonaut, Yuriy Alekseyevich Gagarin, off on his mission. 

As an outstanding scientist and organizer, vice-president of the USSR 

Academy of Medical Sciences and later director of the Institute of Biomedical 
Problems, USSR Ministry of Health, V. V. Parin made a vivid contribution to 
the inception and development of space biology and medicine, its formation as 
a scientific discipline andits practical relevance. V. V. Parin was the 
first editor in chief of the journal, KOSMICHESKAYA BIOLOGIYA I 
AVIAKOSMICHESKAYA MEDITSTNA [Space Biology and Aerospace Medicine]. He 
frequently represented Si siet science at international conferences and con- 
gresses concerned with problems of space exploration. 


[fhe outstanding scientific endeavors of V. V. Parin gained worldwide recogni- 
tion. He was elected academician of the USSR Academy of Sciences and USSR 
Academy of Medical Sciences, doctor honoris causa of Bucharest University 

and Karlow University in Prague, honorary member of the Academy of the 
Socialist Republic of Romania and Romanian Academy of Medicine, honorary 
member of the Czech Medical Society, honorary member of the Czechoslovakian 
Scientific Medical Society imeni J. E. Purkinje, active member of the 
International Academy of Astronautics and vice-president of the International 
Federation of Medical Electronics. 


The research of Academician V. V. Parin in the area of space biology and 
medicine is inseparably linked with all the rest of his scientific legacy: 
work on physiology of circulation, clinical physiology, medical electronics 
and cybernetics. We can arbitrarily single out three directions of V. V. 


144 





Parin's work in the field of space medicine: theoretical research, expert- 
mental work dealing with analysis of results of ground-based and tlight ex- 
periments, methodologica, work concerned with the search, development and 
introduction of principles and methods for assessing the health status of 
cosmonauts, Definition of the basic directions for development of space 
cardiology, formulation of problems of medical prognostication, generaliza- 
tion of the results of work on the main problems of space physiology were 
among the important results of theoretical research done by Vasilly 
Vasil'yevich Parin. 


Creation of space cardiology was 
the logical result of the 


studies pursued by V. V. Parin 
pe in the area of physiology of 
Ya ’ , ’ ’ id 
/ circulation which are unlver- 


sally known. As far back as 

the 1930's-1940's, he investi- 
gated the receptor field of 
pulmonary vessels and studied 
nervous regulation of spleen 
contractions. This work led 

to discovery of the pulmonary 
circulation unloading reflex, 
which protects the right ventricle 
against excessive loads when 

there is elevation of pressure in 
the pulmonary artery. This ref- 
lex was named "Parin's reflex." 
Parin's reflex is one of the 
important mechanisms of regulating 
central hemodynamics in weight- 
lessness. Redistribution of blood 
to the upper part of the body, 
which occurs due to disappearance 
of the hydrostatic circulatory factor, leads to increased delivery of blood to 
the pulmonary vessels. Stimulation of pressoreceptors of the arterial part 

of the pulmonary circulation, caused by elevation of pressure in pulmonary 
vessels, is associated with development of Parin's reflex: arterial pressure 
lrops and pulse slows down. Such a reaction is particularly marked for the 
first few days that cosmonauts are in orbit; subsequently, other mechanisms, 

in particular the Henry-Gauer reflex, activation of the sympathetic part 





of the autonomic nervous system and others acquire prime significance. The 
facts enabled V. V. Parin et al. (1965, 1967) to formulate a theses about 
the circulatory system as an indicator of adaptive reactions of the entire 
body. 


Development of methods of forecasting the functional state of crew members 
during long-term flights was another important result of the theoretical 
research of V. VY. Parin. In 1968, his article, "Forecasting in Space 
Biology," was published, where the methodology of this direction was first 
discussed, which is particularly important to medical support of spaceflights 
lasting many months. In this article, Vasiliy Vasil‘yevich wrote: "Scientific 


145 





and medical forecasting human states is one of the most important problems of 
cosmonautics, and as the duration, range and number of flights increase it 

wil. acquire increasing significance." In the opinion of V. V. Parin, fore- 
casting the health status of cosmonauts should consist of detection of still 
latent functional deviations in the system of controlling physiological 
processes, even before such changes and deviations lead to visible changes in 
the parameters that are monitored, This idea served as the basis of a 
subsequent] developed prognostic approach to evaluation of functional states 
of crews during long-term missions aboard Salyut orbital stations. In essence, 
this approach consists of viewing the body's reactions and, in particular, 
those of the circulatory system to spaceflight factors as stress, which alters 
the degree of their adaptation to ambient conditions. The degree of tension 

in regulatory mechanisms determines the so-called cost of adaptation to a 

given set of stress factors. An excessively high "cost of adaptation” could 
lead to complete depletion of adaptation mechanisms, development of inadequate, 
adverse states or diseases. Thus, the forecasting consists of monitoring the 
tension of regulatory mechanisms, viewing an increase in this tension as a 
prognostically unfavorable sign. 


The theoretical theses of Academician V. V. Parin about the cardiovascular 
system as an indicator of adaptive reactions of the entire body and about 
forecasting by means of detection of deviations referable to mechanisms of 
regulating functions subsequently gained broader application as well in 
public health care practice, in developing the system of preventive 
screening of the public. 


The experimental work of V. V. Parin covers a wide range of problems of space 
medicine and biology. Starting with the flight of Layka aboard the second 
artificial satellite, V. V. Parin was one of the directors of physiological 
research in space. He reported on the results of the studies during the 
first spaceflipit of Yuriy Alekseyevich Gagarin on 15 April, at a press 
conference in the Moscow Scientists’ Club and then in September 1961 at the 
lOth European Congress on Aviation and Space Medicine in Paris. On the 
basis of the results of experimental studies conducted both in the laboratory 
and during spaceflights, V. V. Parin worked out problems of space cardiology, 
problems of reactivity of the body to extreme conditions, as well as problems 
of psychophysiology during spaceflights. The completion of a cycle of biolo- 
gical studies in space was usually associated with publication of comprehen- 
sive fundamental works authored by V. V. Parin. 


VY. V. Parin was the initiator and supervisor of research on the problem of 
simulating the effects of spaceflight factors on man and animals. A set of 
investigations of the effects of hypokinesia on man was deployed under the 
guidance and with the direct involvement of V. V. Parin. V. V. Parin devoted 
much attention to this matter, stressing its social, clinical and applied 
relevance. The studies pursued under the guidance of V. V. Parin established 
the principal patterns of effects of hypokinesia on the cardiovascular system, 
myocardium, regulation of circulation, nervous and hormonal systems. 


The research of Academician V. V. Parin dealing with methodology of investi- 
gations and principles of assessing the health status of cosmonauts merits 
special attention. His interest in these matters never waned. He was one 


146 





of the ploneers in development of medical electronics and blological cybernetics 
in our country. As an experimental phystologist, Vasiliy Vasil’ yevich always 
devoted much attention to searching for new methods that would permit obtaining 
new sclentifie facts, to look deeper into the substance of the biological 
phenomena under study. 


In 1960, in an article entitled "Some of the Results and Prospects of Kesearch 
in the Area of Space Biology," Vasiliy Vasil'yevich wrote: "... in sclentif i 
institutions concerned with the study oi problems of space biology, the know- 
how of physiologists and ... the knowhow and knowledge of engineers and tech- 
nicians should merge into a single, inseparable whole." As a major specialist 
in physiology of circulation, V. V. Parin devoted particular attention to 
development of methods of space cardiology. He was personally involved in 
developing several new methods. Among them, we can mention seismocardiography, 
which was specially developed to examine central hemodynamics of cosmonauts 
during flights. Mathematical analysis of cardiac rhythm is another important 
method, which was first used in space research and for the development of 
which V. V. Parin is to be credited to a ,agnificant extent. This method tis 
used during long-term flights aboard the Salyut orbital stations to assess 
tension of regulatory systems, in particular, autonomic regulation of the 
circulatory system. One important direction of the work done by V. V. Parin 
is related to mathematical analysis of medical and physiological data, i.e., 
1utomation of data processing. Vasiliy Vasil'yevich was an active proponent 
of development of onboard computers to assess the inflight condit ion of 
cosmonauts and transmit data to the ground in "compressed" form. Several 
studies in this direction were pursued under his guidance. 


At the present time, space medicine has had over 20 years of experience in 
examining man in flight. The creative route traveled by Vasilly Vasil'yevich, 
which culminated with research in the area of space biology and medicine, was 
4 continuous chain of interrelated stages of scientific research. The chain 
of this research can be defined as investigation of mechanisms of regulating 
functions, in particular, the circulatory system. V. V. Parin realized well 
that much depends here on methods of investigation, means of gathering and 
analyzing information. Vasiliy Vasil'yevich actively called upon representa- 
tives of allied disciplines to discuss new experimental facts; he made broad 
use of mathematical models and the ideas of biocybernetics. He boldly used 
nontraditional methods and nonstandard principles to solve pressing scientif le 
problems. The results of the studies VY. V. Parin pursued in the 1950's- 
1960's retain their relevance in our time, including space medicine. 


In the 1950's, V. V. Parin instigated development and introduction to 
practice of Soviet medicine of a new method of studying heart function-- 
ballistocardio;s,raphy, which consists of recording microscopic body movements 
related to the impulse and recoil when blood is ejected from the ventricles 
into the great vessels. This technique makes it possible to assess the 
force and coordination of cardiac contractions, correlation between 
activity of the right and left heart. This method gained use primarily in 
preventive medicine for detection of early and still compensated changes in 
central hemodynamics. In 1979, the first ballistocardiogram was taken in 
weightlessness. In 1981-1982, systematic ballistocardiographic tests were 


147 








nade on crews during 185=- and 2lleday flights. New facts were obtained, 
inalysis of which could not be complete without consideration of V. V. Parin's 
research on pulmonary circulation and clinical physiology of circulation. 

V. J. Parin also made a large contribution in the area of analysis and evalu- 
ation of ballistocardiograms. Ballistocardiography in weightlessness, which 

was first done in our country, can be considered a continuation of the work 

in the area of ballistoc*rdiography as it applies to problems of space medicine, 
which was started by Academician V. V. Parin. 


[t should be noted that V. V. Parin and his disciples were able to make such 
high achievements in space medicine, particularly space cardiology, because 
their work was based on his fundamental research on physiology and patho- 
physiology of the heart and clinical studies on human physiology. He was 
ible to utilize for space medicine the most valuable achieyements of Soviet 
and world science. This was largely instrumental in the tapid and fruitful 
levelopment of Soviet cosmonautics, which has justifiably gained worldwide 
recognition. 


OPYRIGHT: "Kosmicheskaya biologiya i aviakosmicheskaya meditsina", 1983 


1s , , 
f 
LU,OD/ 


CSO: 1849/6 - END =