by Academicians Oleg GAZENKO and Anatoly GRIGORYEV; Anatoly YEGOROV, Dr. Sc. (Mcd.); State Research Center-Institute for Medico-Biological Problems, Russian Academy of Sciences

Piloted astronautics has made a giant leap since the trailblazing flight of Yuri Gagarin in April 1961. This is no longer fiction but routine work as space crews stay within orbital stations for many months on end. However, their onboard physical comfort is next door to the hostile environment of the void. Warding off its hazards is a formidable job that can be tackled none the less...

FIRST STEPS

The medico-biological problems of space flights were first addressed by the Russian scientists Konstantin Tsiolkovsky (1857 - 1935) and Friedrich Zander (1887 - 1933) as well as their counterparts abroad-Robert Esnault-Pelterie (1881 - 1957), Hermann Oberth (1894 - 1989) and others. The progress of rocket engineering (Werner von Braun in Germany and later, in the United Stated, Sergei Korolyov and others in the Soviet Union) in the 1940s and 1950s enabled biological experiments first in suborbital (1949) and then in orbital flights. The first tests of this kind were performed by John Henry and Otto Gauer of the United Slates on squirrel monkeys and mice. Up until 1951 it had not been possible to keep those animals alive, though using biotelemetry, investigators could register EKG, respiration, body temperature and other vital parameters.

In our country investigations in this area were begun in the summer of 1951 by the personnel of the Air Force Institute for Aviation Medicine on the spacedrome Kapustin Yar. Sending up rockets with dogs and other animals to 100 - 450 km, experimentalists could not detect any substantial disorders in the organism of the test animals when they stayed in weightlessness for as

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The range of adaptive changes in a cosmonaut's organism in endurance flights and during readjustment to ground conditions.

long as 8 minutes, and during their ejection and subsequent parachuted descent. Carried out by Vladimir Yaz-dovsky, Alexander Seryapin, Abram Ghenin and other experimentalists, such launchings-aside from physiological observations-were also meant for developing life support and rescue systems for pilots of rocket planes. However, at that stage one could not go deep into the effect of prolonged zero gravity on biological objects. The tables were turned with the launching in the Soviet Union of the first artificial satellite of the earth (sputnik)in October 1957.* Next, in November 1957, the first living being-the dog Laika-was carried aloft. Thereupon came successful flights with dogs and other test-objects. These projects were carried out with active assistance from Academicians Vassily Parin, Norayr Sisakian, Vladimir Chernigovsky Vladimir Engelgardt and other big-name scientists. In bioexperiments inestimable support came from Acad. Anatoly Blagonravov, Mstislav Keldysh and Sergei Korolyov, our Chief (General) Designer of spacecraft.

We studied responses of different organisms to space flight conditions and tested life support systems, control methods and emergency rescue techniques. The evaluation of all these data invited this conclusion: man-in-space flights were possible indeed.

By 1959 the first group of prospective astronauts (or cosmonauts as we say) was picked from among young fighter plane fliers (Nikolai Gurovsky, Ivan Bryanov, Yev-geni Fyodorov, Yevgeni Karpov and others). They went through a period of preflight training completed by the spring of 1961; here particular attention was given to medical aspects and tolerance of the human organism to stres-sors, such as g-loads, heat, hypoxia (oxygen starvation), low barometric pressure, weightlessness and the like.

Yuri Gagarin's pioneering orbital flight took place on April 12, 1961, aboard the Vostok spaceship. Taking 108 minutes, this mission was an epic achievement for our country**; simultaneously, it ushered in an age of aerospace medicine as a new science. Many research centers became involved in space medicine studies and projects. In 1963 the USSR Health Ministry set up a goal-oriented research center, the Institute for Medico-Biological Problems (IMBP), which is still a head organization handling problems of medical support of long space flights and all-round testing of hardware.

SHORT FLIGHTS

First and foremost, our experts are concerned with such problems as the effect of flight factors on the

* See: V. Senkevich, "Russian Cosmonautics at the Turn of Two Centuries", Science in Russia, No. 1, 2001. - Ed.

** See: A. Orlov, "He Opened Window into Space", Science in Russia. No. 4, 2004. -Ed.

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human organism and modes of protecting it from all the various hazards. Also, with onboard life support and equipment, and adequate physiological and hygienic standards. Furthermore, we take care of facilities for rescue operations of crews in distress or in emergency situations as well as medical control, prevention and treatment of associate diseases. This work is based on the achievements of aerospace physiology, radiobiology, hygiene, medical expertise and many other areas of theoretical and clinical medicine.

Since, owing to scientific and technological progress, "orbiter houses" provide ever more comfort and amenities to the crews, only a limited complex of stressors acts upon the human organism, and these are: overloads upon takeoff and descent; weightlessness from the moment of injection into orbit up to the initial leg of the homebound journey; emotional and nervous stresses caused by an enhanced sense of responsibility while in flight; also, the strange environment and the constant threat of unexpected emergencies... Finally, ionizing radiation is always much around. But if flights occur below the radiation belts of our planet and if there is a quiet, undisturbed sun, this kind of radiation, though it exceeds the ground level, lies within safe bounds.

Now what concerns zero gravity, or weightlessness: at the present stage our knowledge is not sufficient yet about its aftereffects for human health, capacity for work, reproductive functions and life expectancy. And we were all the more ignorant about that forty-five years ago. Opinions were poles apart then. The optimists maintained weightlessness as such was essentially unable to upset the course of vital biological processes-what it did was to cause physical discomfort. Objecting, the pessimists argued that in the process of his phylogenetic evolution man had never confronted this phenomenon and, therefore, lacked evolutional mechanisms of protection. Hence staying long in weightlessness posed a health hazard.

Since these two viewpoints were not backed by experimental proof then, we had to proceed cautiously in increasing space flight duration. The medical examination of our first cosmonauts upon their return to earth did not defect any substantial disorders in their health apart from moderate symptoms of geodynamic and locomotor disturbances. This inspired our space boffins-so much so that they dropped the subject of prolonged man-in-space journeys.

But then something happened. In June 1970, after their 18-day space mission on board Soyuz-9, the crew betrayed symptoms of significant disturbances. The fitness to work of the spacemen Andrian Nikolayev and Vitaly Sevastyanov was much below normal during their first days back on earth-what's more, they could hardly keep a body's upright position. Furthermore, they experienced dyspnea and tachycardia, and showed locomotor disorders when walking and running. Even though these symptoms were transient and did not last long, the disturbances were clearly on hand, and the optimists, disheartened, lay low.

As Abram Ghenin, one of the space medicine pioneers, recalled, the condition of the cosmonauts was discussed in detail at the Second Scientific-Technical Conference held on the 15 - 18 December 1970 at the Space Training Center under General Nikolai Kamanin, Assistant Air Force Chief. The conferees agreed that 18 days was the outside endurance limit for weightlessness, and that subsequently the rate of increase in the duration of space flights should not exceed twenty-four hours. Accordingly, one questioned the expediency of long-term piloted stations in orbit-at that time under construction in the Soviet Union and the United States.

Back in 1964 to 1966 experts of the Research Institute of Aerospace Medicine and Institute for Medico-Biological Problems (IMBP) had worked out a program for security on long space flights. An essential part of that program were ground laboratory tests simulating the physiological effects of zero gravity. Visualized as the most probable targets of negative effects were the heterogenic (different) macrostructures of the organism of man and animals, that is whole organs and systems, but not microstructures for one knew that with a decrease in an object's mass the gravitational and iner-lial forces acting upon it decreased proportionally. However, the forces of molecular interaction determining the viscosity of a medium as well as the diffusion and kinetics of chemical reactions do not depend on the magnitude of gravitation, and their relative role tends to increase. These considerations furnished a basis for the hypothesis on the essential possibility of averting unfavorable aftereffects of man's long stay in weightlessness: this could be achieved by imitating weight loads on the locomotor, cardiorespiratory and other systems of the organism.

Such studies involved broad cooperation of researchers from the best laboratories of the Soviet Union, the United States, Japan, Czechoslovakia, Poland, Hungary, France, Bulgaria and Romania. This work was coordinated by the INTERKOSMOS Agency of the USSR Academy of Sciences. It was proved in the long run that zero gravity does not produce any outright noxious effect on basic vital processes at the cellular and subcellular levels with no rigorous gravity orientation implicated on the microlevel, while the biological aftereffects appeared to be due to the impact on the entire organism.

Model endurance experiments (up to a year) at ground laboratories with volunteers imitated the primary effect of weightlessness on the cardiorespiratory, locomotor and other systems. Also studied were the psychic and physiological responses of a small group of test-subjects to long isolation within an orbiter dummy.

The 23-day space mission of Georgi Dobrovolsky, Vladislav Volkov and Viktor Patsayev aboard the first

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orbital station Salyut-I in June 1971 was an acid test for the experimental results. Up until the final day the flight proceeded without a hitch. However, as the descent module of the transportation space vehicle Soyuz-II made a touchdown, the cosmonauts were found stone dead, "without any signs of life", as the official report said. The first scenario that the crew died because of the descent overloads after prolonged stay in weightlessness proved wrong. As it was, however, the descent module came to be depressurized soon after undocking, and the inside pressure plummeted to zero just within 40 seconds. The men died of acute oxygen want (hypoxia) and decompression. Their long stay under zero-gravity conditions had nothing to do with that. Taking stock of the available data, experts saw that flight duration could be upped.

LONG FLIGHTS

There came other space endurance records. In the past three decades or so, as many as nine piloted orbital stations (OS) were launched: Salyut (1971. 1974, 1975, 1976, 1977, 1982); Mir ( 1988) as well as the US Sky lab (1973), and the present International Space Station (placed in orbit in 2002). A huge amount of work was accomplished in studying extraterrestrial and outer space, our home planet earth and man's condition on endurance space missions. A good deal of attention was given to aerospace medicine and gravitational physiology, an important factor for coping with the job of medico-biological life support of space crews.

Owing to new elements of the medical control and monitoring system at the OS Mir, it became possible to set several space endurance records culminating in the superlong 438-day mission of the space medic Valery Polyakov. Tested at this orbiter were effective remedies of medical assistance on board and of post-flight rehabilitation back on earth. This work went on nonstop during the fifteen years of Mir's life in orbit, with 62 cosmonauts and astronauts taking turns (many went on repeat missions), including six medics from Russia, the United States and France.

The physiological and biological studies made during and after these missions yielded a wealth of data on the vital activity of the human organism under extreme conditions and on psychic responses and capacity for work vis-a-vis dynamic overloads. New regularities were discovered for adaptation of the functional systems of the organism to gravitational differentials, and valuable experience was gained in the socio-psycholog-ical backing of physical fitness of crews exposed to longtime stresses in solitude. All that was naturally taken into account for upgrading onboard security and safety. The hygienic, microbiological and radiation-physical investigations enriched our knowledge of the dynamics of processes occurring in the confinement of orbital complexes. We acquired experience in the medical and sanitary maintenance of space crews on board. Experiments on higher plants, amphibia, snails and other biological objects furnished valuable information for the subsequent designs of better biological life support systems.

Good headway was made in developing medical research equipment, and in improving the computer-aided system of collecting, processing and storing medico-biological data, and in compiling an experimental databank.

A number of major joint projects were realized at OS Mir with Austria, Germany, France, the European Space Agency and the United States. The experience of joint effort of scientists from several countries in piloted astronautics problem solving laid a solid groundwork for the International Space Station (ISS) and, as we hope, may be helpful for a prospective expedition to Mars, which is a special chapter of the story.

A set of variable factors acts upon a space traveler, and their combination changes from flight to flight and even during one single space expedition. All that hampers data evaluation relevant to the condition of the organism and its functions. It stands to reason that the physiological impact of these factors can be studied at

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ground-based laboratories. But for obvious reasons this does not hold for zero gravity, which is dominant and ever-present on man-in-space missions. Weightlessness is responsible for adaptation toward an adequate relationship of the organism with a complex of the "lower demands" of the environment. This causes phenomena of "disuse" and later of "atrophy from inaction". As to the functional changes, these are due to three chief causes: changes in the afferent* link of the nervous system, abolition of the blood hydrostatic pressure, and zero weight load on bone and muscular tissues.

Now the very first effect of weightlessness is manifested in the illusions concerning body posture or transposition in space. Such illusions are connected with faults in the hitherto well-coordinated performance of the vestibular apparatus of the ear, visual aberrations, and mismatches of skin and muscle sensitivity. You feel as though you were falling or flying head down. The physical discomfort is enhanced by vertigo (dizziness), weakness, nausea, hypersalivation and even vomiting. The time and indication of such symptoms vary with different individuals, but they are observed to some extent in more than half of the persons exposed to weightlessness while in orbit. The "space, or motion sickness" became a barrier in the way of manned space exploration.

In the course of their extensive studies, Dr. Lyudmila Kornilova and coworkers succeeded in identifying the causes of sensory anomalies. They made a study of visual fixation processes, and detected faults expressed in the diminished rate and accuracy of visual tracking. One could get over this barrier through a "vestibular selection" of the hardiest candidate cosmonauts, by preflight training sessions, and other preventive procedures. Thus we managed to arrest such disturbances.

Likewise important are reactions triggered by the abolition of hydrostatic blood pressure. Turning weightless, the circulating blood is redistributed-it is rechanneled from the lower to the upper part of the body, and its ever increasing influx expands its intratho-racic (within the chest) volume. The nerve receptors controlling the mass and pressure of circulating blood respond to this situation as an emergency one. So mechanisms cutting the circulating blood volume are switched on. The decreasing output (secretion) of re-nin and angiotensin, the hormones regulating water-and-salt metabolism, is also playing a substantial part; as a result, the kidneys discharge an increased amount of water and electrolytes. The phenomenon of hypodipsia occurs, and a negative water balance is established. This explains the weight loss on a space flight's initial stretch. The outward symptoms arc manifested in hyperemia ("rush of blood"), face oedema (swelling) and eye reddening. As a consequence, in two or three weeks one can develop symptoms of cardiovascular untraining. As a matter of fact, the state of the cardiovascular system got a priority attention, and so essential indicators were registered from start to finish. Ultrasound studies made by the space medic Valery Polyakov and Dr. Galina Fomina of our staff showed that in weightlessness during quiescence there develops a syndrome of moderate hypovolemia (a drop in the volume of circulating blood) expressed in a fall of systolic (arterial) pressure, in the contraction of cardiac cavities and in the lower resistance of the renal artery against the persisting contractive and pumping function of the heart.

Symptoms of hypervolemia (increase in the volume of circulating blood) and venous congestion were diagnosed in and about the head and within lesser blood circulation. Indications of relative hypovolemia, diminished blood flow and resistance of the femoral arteries were detected in inferior limbs. The femoral veins showed constrictions in their lumen. Such changes were observed in space crews in other endurance flights as well.

* Afferent (Physiol.) - bringing to or leading toward a central body or point. - Ed.

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The lower body negative pressure test (analog of the orthostatic test imitating redistribution of blood whereby it is deposited in the region of the lower extremities, which is characteristic of man's upright posture on the ground) resulted in the diminished capability of femoral vessels in counteracting the blood flow to the body inferior part. This was accompanied by a decreased efficiency of cerebral circulation due to changes in the resistance of the brain's vessels. It was demonstrated in the final analysis: the post-flight reduction of orthostatic competence (assessed by responses of the organism to changing from the prone to the upright position) is largely determined by the condition of blood vessels of the legs and by the regulation of the tone of cerebral and femoral blood vessels. These data are important for methods of preserving orthostatic stability upon touchdown.

Persisting weightlessness gives rise to responses resulting from the abolition of weight loads on the bone and muscle system. The underloading of muscles, tonic ones in particular (which are responsible for body postures), leads to their partial atrophy. This affects protein and electrolyte metabolism and upsets the overall ener-

gy budget of the organism. The locomotor activity pattern undergoes appreciable changes: man docs not walk, he kind of swims within a spaceship. The muscular mass contracts, chiefly at the expense of the lower limbs and the back.

The joint Russian-Austrian studies carried out by the teams of Prof. Frank Gerstenbrandt and Inessa Koz-lovskaya, RAS Corresponding Member, detected diminished strength indicators of extensor muscles induced by zero gravity, though less pronounced in the flexor muscles of the leg. These effects were not abolished by prophylactic remedies during the first month in orbit. But they tended to normalize later on largely thanks to preventive physical training.

Osteoporosis was diagnosed in bone tissue, the aftereffect of the loss of calcium and phosphorus. Thus far changes in skeletal hardness did not pose any major threat. But these phenomena need further investigation.

The immune system showed a decrease in cellular and antiviral activity but no changes in humoral immunity. The amount of erythrocytes and hemoglobin in blood was down.

Yel by far not all changes in a space traveler's organism can be explained by the effect of zero gravity. Thus, changes in the man/microorganisms system result from staying within a confined, hermetic space, diet peculiarities, modified reactivity of the organism and last, from the variability of microorganisms themselves. All that must be the cause of deviations of some of the immunity indicators in orbit.

Still and all, considering the available experience, our impression is that human beings are capable of adjusting to persisting effects of weightlessness. Apparently this must be due to the physiological and partly, anatomical, moditlcation of the organism. The reverse side of the coin are troubles connected with the readap-tation to customary terrestrial conditions. All spaceper-sons have experienced such troubles upon touchdown. The hard and occasionally painful process of readjustment is the biological price paid for the privilege of seeing the globe from the orbit.

Hence the medical support strategy: use moderate physiological adaptation to zero gravity so as to avoid or alleviate the readaptation troubles.

HEALTH MONITORING

The chief purpose of aerospace medicine is to keep space crews fit for many years ahead. This is achieved by the system of health monitoring that has proved its worthiness and efficiency in practice. Its elements include: onboard environmental and food quality control-also, over proper water supply, personal hygiene and physical comfort; medical operational monitoring and treatment; evaluation of a crew's psychological status and efficiency; fault and error detection in job performance; adequate rest and sleep. If necessary, the

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daily routine and work schedules are readjusted, and a crew is pepped up psychologically.

Operational medical control is practiced on active flight legs and during extravehicular activity (EVA). This takes in EKG and respiration rate readings. During an egress into raw space for EVA a cosmonaut's body temperature is double-checked; this goes along with suit temperature and suit-to-ambient differential pressure control so to assess the organism's thermal status.

Thorough medical examinations occur on a regular basis, and these include monitoring of the cardiovascular and muscular systems, standard training regimens, biochemical urinalysis and blood count by the "dry chemistry" method (via a system of specific indicators), immunological studies and other procedures. An onboard array of instruments records EKG, arterial pressure, regional hemodynamics and other indicators, and transmits these readings to the ground control center. Proceeding from different combinations of the above parameters, we draw up programs for checkups on the rest stale as well as on functional test runs involving dosaged, graduated three-stage loads on the veloergometer and negative pressure applied to the body inferior part.

Examining the muscular system, medics measure the body and crural mass and, using a special test, evaluate the efficiency of standard physical training regimens. It involves a 5-stage locomotor trial (walking, running) on the treadmill supplied with simulated (artificial) gravity of about 50 kg. This is followed by additional control exercises with expanders for the dynamic and static tolerance of the musculature. To get ready for EVA cosmonauts take veIoergometric runs with hand and foot pedaling for testing their total muscular stamina and checking on the attendant responses of the cardiovascular system.

Biochemical blood counts arc taken by using REFLOTRON, a device for assaying biochemical indices of the organism's liquid media by the "dry chemistry" method; blood morphology under space flight conditions is tested with the use of the MIKROVZOR setup (which is a microscope hooked to an onboard transmitter plus a case with fixings needed for hemo-analysis).

The sanitary and hygienic monitoring of the onboard environment keeps track of air, temperature and humidity parameters, including the automicroflora, the microbial pollution of indoor surfaces, the microimpu-rities in the gas medium and their formative processes.

Indepth medical tests also draw upon the data of medical and physiological observations obtained during extensive research programs.

Prophylactic steps comprise physical exercises on the treadbahn (treadmill) and on velo- and resistance trainers which, in the opinion of Drs. Inessa Kozlovskaya and Viktor Stcpantsov, are helpful in sustaining a crew's working efficiency, for G tolerance (including positive g-force and negative g-force tolerance) and overall endurance. Such exercises boost motor coordination and fitness of the cardiovascular and other systems of the organism. G spacesuits arc prescribed for long wear (from 8 to 10 h daily) to simulate weight load on bones and muscles along the body's longitudinal axis and reproduce a definite degree of deformation and activation of the locomotor mechanoceptors. The preventive setup is also equipped with multichannel electromyo-stimulators (pacers) for skeletal muscles so as to preclude their atrophy.

Preventive medication is administered to all crew members at regular intervals. According to Dr. Igor Goncharov, such prophylaxis provides for a course of cardiotropic medication to prevent metabolic changes in the myocardium; of nootropic preparations against possible asthenoneurotic conditions; of bifidumbacterin for postural equilibrium and for a proper quantitative correlation and composition of the intestinal microflora... And so on.

At the closing stage of an orbital flight preventive measures are taken to brace up a cosmonaut's organism for gravitational stresses on the descent trajectory. For this purpose negative pressure is applied to the body's lower part. That is, hydrostatic blood pressure in the vascular bed of the legs is reproduced at zero gravity. Supplementary prophylaxis includes remedies that help retain fluids and electrolytes within the organism (this is done by applying negative pressure to the body lower part with the aid of the CHI BIS spacesuit and by water-and-salt additives to food) and boost the orthostatic competence upon touchdown. We should also mention anti-g suits for descent; these, according to Dr. Adil Kotovskaya, inhibit blood deposition in inferior limbs and thus alleviate overloads and post-flight orthostatic complications. All that facilitates the readaptation process.

The above means of health protection and monitoring have thus far been used in circumterrestrial space flights only. But some of them are bound to be employed on long-distance space voyages to other planets. This will be the subject of our next story.

(to be continued)

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