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The progress of science and technology at the end of the XIXth and first half of the XXth century paved the way to start space exploration by humanity. The flight of Yu. A. Gagarin on April 12, 1961 was one of the history watersheds that had a great many of social implications. Piloted missions to space demonstrated the possibility for humans to adapt to the spaceflight factors which, nonetheless, can provoke various unfavorable reactions, particularly on return to Earth. Step-by-step extension of mission length paralleled enhancement of the methods of monitoring of crew health, life support systems, and development of modalities to maintain crew health and performance. The paper contains brief discussion of data acquired in short- and long-term missions including the 438-d mission of cosmonaut-physician V.V. Polyakov. The final section is devoted to the mainstream problems of future piloted space programs.

This paper describes the history of the Institute of Biomedical Problems (IMBP): its birth and development. IMBP's directors were: Andrei V. Libedinsky (1963-1965), Vasily V. Parin (1965-1967), Oleg G. Gazenko (1968-1988), and Anatoly I. Grigoriev (1988 to the present). Most of the early employees of IMBP came from the USSR Air Force Institute of Aviation Medicine and the USSR Ministry of Health Institute of Biophysics. The major goals of IMBP were: development of a system of medical monitoring and support of long-duration space missions, selection and training of civilian crew members, bioengineering testing of flight equipment, and development of life support system concepts and requirements. The paper presents major results of the above research activities.

In a brief review of 50-year scientific activity of professor N. N. Sirotinin and his students the authors emphasize that this broad-minded scientist contributed to development of such disciplines as microbiology, pathophysiology, high-altitude, aerospace medicine. However, his main goal was evolution of reactivity and resistance, approaches to perfection of human health and performance. Much attention was paid to effects of low partial oxygen pressure on human and animal body, to hypoxic states of different origin. Methods of hypoxytherapy and hypoxic training are widely used in Russia and abroad. The contribution of academician N. N. Sirotinin to modern pathophysiology, high-altitude and aerospace physiology, internal and sport medicine is highly appreciated in Russia.

In 1987, the USSR cosmonauts Y. V. Romanenko (326 days), A. I. Laveikin (approximately 176 days), and A. P. Alexandrov (approximately 160 days) made a space mission on Mir. (A. I. Laveikin showed specific cardiovascular responses to exercise tests and was therefore replaced with A. P. Alexandrov). The most important medical result of this mission was that Yu. V. Romanenko, who remained in orbit for 3 months longer than anyone before, working intensively, did not exhibit any changes that were qualitatively different from those observed in previous long-duration space flights. The health status and work performance of other crewmembers were also good, although each of them showed individual responses. The postflight recovery period went smooth.

This paper discusses general concepts and specific details of the habitability of space stations and planetary bases completely isolated from the Earth for long periods of time. It emphasizes inadequacy of the present-day knowledge about natural conditions that provide a biologically acceptable environment on the Earth as well as lack of information about life support systems as a source of consumables (oxygen, water, food) and a tool for waste management. The habitability of advanced space vehicles is closely related to closed bioregenerative systems used as life support systems.

During 1982-1986 the orbital complex Salyut-7--Soyuz-T was visited by six long-term (from 65 to 237 days) principal crews and five short-term (from 8 to 12 days) visiting crews. Many medical investigations were performed during those missions, especially during the longest 237-day flight in which a physician-cosmonaut took part. The objective of the investigations was to accumulate new data and complementary information about physiological responses to microgravity. The methods and procedures used were in part the techniques, which were employed in previous missions but modified to meet specific requirements, and in part new techniques such as echocardiography for cardiovascular measurements, various loading tests, sensory tests, and blood and urine biochemistry.

This paper presents medical results obtained in a Salyut-7 8-month manned mission in which a physician-cosmonaut took part. The results include body mass and height measurements, vestibular studies, cardiovascular studies at rest and in response to staged functional loads (with echocardiographic examinations accentuated), metabolic and hormonal studies. The paper also gives information about medical aspects of extravehicular activities. It is emphasized that during the mission both old and new methods of research were used and medical results of preceding flights were considered.

The spawn of the aquarium fish Brachydanio rerio was developing during 5--6 days under conditions of weightlessness (first on board the spaceship "Sojuz-16", then in the space station "Salut-4") in special aquariums "EMKON", in thermostable installations. Electron microscopically the embryos were found to have a well developed labyrinth in early developmental histologically and cytologically differentiated receptory structures of the macula utriculi and macula saccili. In contrast to controls, the experimental animals showed certain alterations in the otolite organization. In similar experiments the embryos of clawed frog Xenopus laevis in the stage of the tail bud were also placed in special containers "EMKON" and thermostable apparatus "Biotherm-4" and by the spaceship "Sojuz-17" were brought to the space station "Salut-4", where it stayed for 16 days. The initial embryos had already had a well developed acoustic vesicle with macula communis. Inspite of the preliminary load by start acceleration and staying under conditions of weightlessness, they reached the general development fairly similar to controls. As it was shown electron microscopically their labyrinth had highly histologically and cytologically differentiated structures. However, a disturbance of the development of the otolithic membrane and otoconia should be noted. The alterations observed in the otolithic membrane organization in experimental fishes and frogs may be explained by general disorders in calcium metabolism.

The program of the 7-day flight of the biosatellite Cosmos-1667 launched in July 1985 included experiments on two rhesus monkeys, ten Wistar SPF rats, ten newts, Drosophila flies, maize seedlings, lettuce sprouts, and unicellular organisms--Tetrahymena. The primate study demonstrated that transition to orbital flight was accompanied by a greater excitability of the vestibular apparatus and an increased linear blood flow velocity in the common carotid artery. The rat studies showed that atrophy of antigravity muscles and osteoporosis of limb bones developed even during short-term exposure to microgravity. The experiments on other living systems revealed no microgravity effects on the cell division rate, proliferative activity of cells of regenerating tissues and organs, energy metabolism of developing insects, structure or chemical composition of higher plant seedlings.

The major goal of biomedical investigations in prolonged (up to 6 months) manned missions was to obtain information about physiological reactions to long-term weightlessness and to carry out detailed clinical, physiological, immunological and anthropometric investigations before, during and after flight. The results obtained give evidence that man can adapt to the prolonged exposure and to maintain good health condition and high work capacity. The changes detected postflight were reversible and disappeared completely within a relatively short time period. The changes were not correlated with the flight duration. The good health condition and high performance inflight were maintained and postflight readaptation was facilitated due to a rational work-rest cycle and specific countermeasures which were modified with respect to the results of regular medical examinations. Salyut-6 medical data have demonstrated that the duration of forthcoming manned missions can be extended.

Four experiments were carried out with mammals (white laboratory rats) in Kosmos biosatellites. The experimental results indicate that rather prolonged weightlessness does not cause pathological changes in internal organs. Changes were discovered in the metabolic and hormonal status of the organisms, allowing us to consider an 18-22-day space flight as a moderately stressful activity. Changes in the musculoskeletal system involved atrophy of particular muscle groups, adaptive transformation of the contractile properties of some of them, osteoporosis, and decreased durability of bony tissue. There was a decrease in the ATPase activity of myocardial myosin, and there were changes in the erythrocytic system: decreased erythrocytic hemopoietic activity, increased levels of spontaneous hemolysis of erythrocytes, etc. All the described changes were reversible, and examination of the animals 25 days after their return to Earth showed practically complete normalization of the parameters studied.

In 1975 the Soviet Union performed two manned flights on board the orbital station Salyut 4. The first mission of 30 days was flown by A. A. Gubarev (Commander) and G. M. Grechko (Flight Engineer) and the second mission of 63 days by P.I. Klimuk (Commander) and V.I. Sevastyanov (Flight Engineer). The present paper gives preliminary data on the general health and cardiovascular investigations of the crew members during and after flight. The clinical and physiological examinations of the cosmonauts showed that the work-rest cycles and counter-measures used helped to maintain their good health and high performance in flight, to alleviate adverse reactions and to facilitate readaptation post-flight. Medical results of the post-flight investigations revealed no changes that may detract from further increasing the duration of manned space missions.

Rat experiments on the Cosmos biosatellites demonstrated that the percentage of renal excretion of consumed water after flight was lower than after synchronous experiment. This can be attributed not only to water retention but also to a different level of extrarenal losses postflight. Weightless rats showed increased sodium excretion after water load tests and increased potassium excretion after potassium load tests. The sodium, potassium, and calcium balance was positive after weightlessness. Analysis of the electrolyte composition of different kidney zones revealed a decreased potassium content in the medulla, which is considered to be one of the causes of changed renal iono- and osmoregulatory function in weightlessness. The normalizing effect of artificial gravity on the natri- and kaliuretic renal function was demonstrated.

Medical results obtained during missions of the Soyuz-12, Soyuz-13, Soyuz-14 spacecraft and the Salyut-3 orbital station are presented. The subjective feelings of the crewmembers (blood rush to the head, chest congestion, vegetative disturbances, etc), data of the inflight medical control and medical experiments as well as countermeasures used are described in detail. Results of postflight medical examinations at rest and using functional tests are also summarized. It is concluded that no abnormalities in the vital physiological functions of the crews developed inflight. The symptoms typical of the acute period of adaptation to weightlessness disappeared completely after the first flight days.

The evolution of the structural, functional and cytochemical organization of the gravity receptor which determines a body position in the gravitational field of the earth by means of muscular regulation was traced both invertebrates and vertebrates, using electron microscopic and histochemical methods. In the course of evolution of vertebrates, the specialized gravity receptor-statocyst which, as a rule, consists of primary sensory cells and supplies otoliths, is formed. In vertebrates, there exists a vestibular apparatus made up of secondary sensory cells and also having otoliths. The receptor cells, both of statocysts and the vestibular apparatus, are supplied with special antennas (kinocilia and stereocilia). Deviation of the antennas stimulated by displacement of the otoliths resulting from locomotor activity of animals leads to excitation of the receptor cells. When exposed to a modified gravitational field (linear accelerations of 10 g, for 3 min), the receptor cells of the vestibular apparatus, in all classes of vertebrates, show progressive changes in RNA content and protein synthesis (increase followed by decrease) which return to normal only after 12 days. Thus, immediate transfer of animals and man from acceleration to weightlessness appears to be a reason for movement disease. The above consideration showed the need for an experiment in which an animal (with its vestibular apparatus) which had not undergone previous accelerations, would be exposed to weightlessness. Frog embryos, Rana temporaria, at the stage preceding the organogenesis, when the vestibular apparatus and other organs were lacking, were chosen as a suitable subject. Frog embryos at the stage of an early gastrula were placed in a special container Emkon aboard the Soyuz 10 spacecraft. After short accelerations, they were exposed to weightlessness for 44 hours. The embryos were allowed to continue to develop to the stage of early tail bud. The experimental embryos showed normally developed acoustic vesicles and vestibular ganglia. Clear differentiation of the receptor cells with antennas (kinocilia and stereocilia) was found in the acoustic vesicles. Thus, in weightlessness, vestibular apparatus develops just as well as in the gravitational field of the earth. However, only a much longer stay in weightlessness conditions will indicate whether there are any changes in the structural, cytochemical and functional organization of vestibular apparatus. The similarity in the structural, functional and cytochemical organization of the gravity receptor in vertebrates and invertebrates appears to allow the prediction of the behaviour of the gravity receptor as a whole, and of its receptor elements, both in normal and changed gravitational fields. The first attempts were carried out only on the vestibular apparatus of vertebrates.

The results of biomedical investigations carried out in the U.S.S.R. manned space missions are discussed. Their basic result is well-documented evidence that man can perform space flights of long duration. The investigations have demonstrated no direct correlation between inflight or postflight physiological reactions of crewmembers and flight duration. In all likelihood, this can be attributed to the fact that special exercises done inflight efficiently prevented adverse effects of weightlessness. However, human reactions to weightlessness need further study. They include negative calcium balance and anemia as well as vestibulo-autonomic disorders shown by crewmembers at early stages of weightlessness. Attention should be given to psychological, social-psychological and ethical problems that may also limit further increase in flight duration.

The changes observed during flight on the whole corresponded with the preflight prognosis and reflected the phase nature of the processes of adaptation. They were shown by blood redistribution symptoms, fluctuations in the main indices of hemodynamics at rest not going beyond the limits of the physiological norm, an increase in the pulse-filling of the head with blood, and a decrease in that of the shank. The reaction of the blood circulation to a physical load and the application of negative pressure varied, and in a number of investigations during flight it was more pronounced than on Earth. The changes observed after the flight appeared regular for the period of readaptation of the reactions of the organism. These reactions bore a functional nature and qualitatively did not differ from reactions observed after other flights, and after the 140-day flight they were, on the whole, less pronounced than after the 96-day flight. In the postflight period to accelerate the process of adaptation a complex of restorative-healing measures was carried out, including mainly a regulation of motor activity, restorative massage of the muscles, remedial physical culture and aquatic procedures. The flight lasting 140 days revealed no contraindications to a further regular increase in the time of cosmic flights and demonstrates once again the possibility of the planned control of the state of a healthy subject in flight and the readiness of the organism for a return to the terrestrial force of gravity.

In prolonged manned space flights, the cardiovascular function was examined at rest and during provocative tests. As compared to the preflight data the following changes were seen: higher heart rate at rest and during LBNP tests, decrease of stroke volume at rest and during LBNP test and a less marked increase (or decrease) during exercise tests, symptoms of a greater heart load which transformed to the syndrome of myocardial hypodynamics (preload) during LBNP tests or to the syndrome of myocardial hyperdynamics (afterload) during exercise tests (with other than preflight ratios of systolic and diastolic time intervals). The above cardiovascular changes did not, as a rule, aggravate with flight time and can be viewed as adaptive reactions to microgravity. The above cardiovascular changes were primarily produced by fluid redistribution in the cranial direction, diminished participation of the muscle system in circulation, and involvement of unloading reflexes from the cardiopulmonary receptor zones.

This paper presents the results of measuring central and regional (head, forearm, calf) hemodynamics at rest and during provocative tests by the method of tetrapolar rheography in the course of Salyut-6-Soyuz and Salyut-7-Soyuz missions. The measurements were carried out during short-term (19 man-flights of 7 days in duration) and long-term (21 man-flights of 65-237 days in duration) manned missions. At rest, stroke volume (SV) and cardiac output (CO) as well as heart rate (HR) decreased insignificantly (in short-term flights) or remained essentially unchanged (in long-term flights). In prolonged flights CO increased significantly in response to exercise tests due to an increase in HR and the lack of changes in SV. After exercise tests SV and CO decreased as compared to the preflight level. During lower body negative pressure (LBNP) tests HR and CO were slightly higher than preflight. Changes in regional hemodynamics included a distinct decrease of pulse blood filling (PBF) of the calf, a reduction of the tone of large vessels of the calf and small vessels of the forearm. Head examination (in the region of the internal carotid artery) showed a decrease of PBF of the left hemisphere (during flight months 2-8) and a distinct decline of the tone of small vessels, mainly, in the right hemisphere. During LBNP tests the tone of pre- and postcapillary vessels of the brain returned to normal while PBF of the right and left hemisphere vessels declined. It has been shown that regional circulation variations depend on the area examined and are induced by a rearrangement of total hemodynamics of the human body in microgravity. This paper reviews the data concerning changes in central and regional circulation of men in space flights of different duration.

This paper presents the results of medical investigations performed in the Salyut-7 8-month mission in which a professional physician took part. The paper contains anthropometric measurements, results of investigating the vestibular function, cardiovascular function at rest and in response to multi-step tests (with emphasis on echocardiographic measurements), metabolic parameters and hormonal status. It also discusses medical aspects of the extravehicular activity. The medical investigations, although some new methods were applied, provided the continuity of methodical approaches and data accumulated in previous missions.

The water-salt supplement developed in ground-based experiments in order to increase human tolerance to LBNP and orthostatic tests was recommended to be given to the crewmembers at the final stage of the second expedition of Salyut-4. On the 53rd flight day, concomitantly with an intake of 4.0 g sodium chloride and 900-1200 ml water, an LBNP test was carried out to assess the effectiveness of this supplement, to select its optimal doses and to clarify individual responses. After the intake both cosmonauts showed a better tolerance of the LBNP test. They also displayed individual variations in their responses, viz. the commander in arterial circulation, and the flightengineer in venous circulation. As suggested by the ground-based experiments and the inflight provocative test, both cosmonauts were requested to take 9.0 g sodium chloride and 1000--1200 ml water on the last flight day. The postflight examinations demonstrated that the countermeasures applied (physical exercises, LBNP) in combination with the direct action on the fluid-electrolyte metabolism gave a pronounced positive effect.

The paper reviews the major results of experiments on microorganisms, plants and animals flown onboard space vehicles during the past two decades. To explain the experimental findings, it is hypothesized that living beings develop an indirect adaptation to gravity effects which has a bearing only on the phylogenetic process.