Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.

For the scientific community, the ability to fly mice under weightless conditions in space offers several advantages over the use of rats. These advantages include the option of testing a range of transgenic animals, the ability to increase the number of animals that can be flown, and reduced demands on shuttle resources (food, water, animal mass) and crew time (for water refill). Mice have been flown in animal enclosure module (AEM) hardware only once [Space Shuttle Transport System (STS)-90] and were dissected early in the mission, whereas rats have been flown in the AEM on >20 missions. This has been due, in part, to concerns that strong and annoying odors from mouse urine (vs. rat urine) will interfere with crew performance in the shuttle middeck. To screen and approve mice for flight, a method was developed to evaluate the odor containment performance of AEMs housing female C57BL/6J mice compared with AEMs housing Sprague-Dawley rats across a 21-day test period. Based on the results of this test, consensus was reached that mice could fly in the AEM hardware for up to 17 days (including prelaunch and contingency) and that the AEM hardware would likely contain odors beyond this duration. Human sensory and electronic nose analysis of the AEMs postflight demonstrated their success in containing odors from mice for the mission duration of STS-108 (13 days). Although this paper focuses specifically on odor evaluations for the space shuttle, the concern is applicable to any confined, closed-system environment for human habitation.

Experiments were carried out on peripheral blood leukocytes and spleen lymphocytes from 29 male rats that were flown during the Spacelab Life Sciences 1 (SLS-1) nine-day mission on the shuttle Columbia in June 1991 and on appropriate ground controls. On the day of landing, there was a significant decrease in the total white blood cell counts (P < 0.0001) of flight animals in comparison to controls. There was also a significant decrease in the absolute number of lymphocytes (P < 0.0001) and monocytes (P < 0.0001) in the flight animals. A slight decrease in the absolute number of eosinophils and a slight increase in the number of neutrophils were observed at landing, compared with preflight values. Immunophenotyping of the peripheral blood and spleen lymphocytes of flight and control animals indicated that, on the day of landing, there was a decrease in the absolute number of CD4 and CD8 positive cells and B lymphocytes. However, relative percentages of peripheral blood CD4+, CD8+, and B cells were not found to be depressed. No differences were discerned in the percent reactivity of spleen lymphocytes of flight animals compared with controls. The observed decrease in the number of leukocytes and lymphocytes at the immediate postflight period was transient and all values returned to the control levels by nine days postflight.

Hindlimb hypokinesia was induced in young and old rats. After 3 weeks, the activities of five enzymes have been measured in soleus and medial gastrocnemius muscles. Soleus showed increased activity of hexokinase and decreased activity of phosphofructokinase, lactate dehydrogenase and malate dehydrogenase in both groups. The activity of 3-hydroxyacyl-CoA-dehydrogenase was decreased in the old muscle. Medial gastrocnemius showed decreased activity of phosphofructokinase and lactate dehydrogenase in both groups. The activity of 3-hydroxyacyl-CoA-dehydrogenase was decreased in the old muscle whereas hexokinase increased its activity in the young one. It is concluded that suspension hypokinesia results in changes at the enzymatic level. These changes appear to be related to the age of the muscle and to its fibre composition.

To determine if the atrophic process was different in the young and in the aged slow-twitch soleus muscle, in which the aging process is clearly apparent, hind limb hypokinesia/hypodynamia was induced. After 3 weeks, we measured speed-related indices, tension indices, and tension producing capacities. Fiber type composition and fiber cross-sectional area were also investigated. After the treatment, body weight and muscle weight decreased, the most important loss being measured in the young group. The ratio of muscle weight to body weight was not altered by hypokinesia/hypodynamia but this ratio was greater in the 3-month-old control group than in the 22-month-old group. Contraction time and half-relaxation time decreased in both groups. In the control group, the old soleus muscle was slower to contract and relax than in the young muscle. Tension indices and tension producing capacities decreased. These included twitch tension, maximally developed tension, force generated per gram muscle, and specific tension. The mean muscle area and muscle weight of the young soleus decreased more than that of the old soleus. The fiber cross-sectional area was reduced in both groups whereas fiber type composition remained the same after hypokinesia/hypodynamia. The suspension atrophy appeared to be independent of age in the soleus at the contractile level whereas atrophy was greater in the young muscle at the morphometric level.

Preliminary results of the radiobiological experiments carried out on the biosatellite Cosmos 690 with a radiation exposure unit on board are presented. The duration of the satellite flight was 20.5 days. On the tenth day of the flight 35 rats were exposed on board the satellite to 220 or 800 rads of gamma radiation. Comparison of data obtained in test and control groups of animals has shown that under the influence of space flight factors a somewhat more severe radiation injury develops than in on-ground conditions.

In the 18.5-day flight of the Soviet biosatellite Cosmos-936 (3-22, August 1977) com-parative investigations of the physiological effects of prolonged weightlessness (20 rats) and artificial gravity of 1 g (10 rats) were carried out. Throughout the flight artificial gravity was generated by means of animal rotation in two centrifuges with a radius of 320mm. Postflight examination of animals and treatment of the flight data were performed by Soviet scientists in collaboration with the specialists from Bulgaria, Czechoslovakia, the German Democratic Republic, Hungary, Poland, Rumania, France and the U.S.A. During the flight the total motor activity of the weightless rats was higher and their body temperature was lower than those of the centrifuged animals. Postflight examination of the weightless rats showed a greater percentage of errors during maze an increase in water intake and a decrease in diuresis; a fall of the resistance of peripheral red cells; an increase in the conditionally pathogenic microflora in the mouth; a decrease of oxygen consumption, carbon dioxide production and energy expenditures; a drop in the static physical endurance; a decline in the capacity to keep balance on the rail; an increase in the latent period of the lifting reflex, etc. The centrifugal animals displayed lesser or no change of the above type. These findings together with the biochemical and morphological data give evidence that during and after flight adaptive processes in the centrifuged rats developed better.

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.

Morphobiochemical investigations of the rats flown on the biosatellite Cosmos-1667 have shown that the 7-day space flight produces shifts in different systems, organs and tissues which reflect adaptive processes to microgravity. Early signs of structural, functional and metabolic rearrangement can be detected in the musculoskeletal apparatus, hemopoietic system, lymphoid organs, neurohormonal systems, i.e., in the systems and organs that develop changes during long-term flights. The rates of adaptation to microgravity are different not only in various systems and organs but also within the same tissues. Most shifts that emerge at an early stage of adaptation to microgravity progress with flight time but some of them develop to a full extent after the 7-day flight. The specific feature of the early stage of adaptation to microgravity is the lack of significant changes in blood biochemistry in the presence of structural and metabolic changes in tissues. This fact gives evidence that the mechanisms maintaining homeostasis at the organism level are not as yet disrupted during 7 days of flight.

A morphological examination of 27 rats flown onboard the biosatellite and sacrificed on the 1st-2nd and 26-27th postflight days demonstrated no significant changes in the structural organization of the vital organs and systems of the animal body. It was, however, found that the space exposure induced morphologically detectable changes in the musculo-skeletal system, hemo- and lymphopoiesis, hypothalamic-pituitary-adrenal system and the juxtaglomerular apparatus of the kidneys. The changes were reversible and nonspecific, and could be seen in animals exposed to ground-based hypokinetic and other stress experiments. Postflight the animals developed some reactions that were similar to those in humans. This helps to identify the morphological substrate of certain changes in the human body and to investigate their pathogenesis.

In 1974 a rat experiment was carried out onboard the Cosmos-605 biosatellite. Inflight Wistar rats were kept unrestrained in small cages. The cages were equipped with a feeder, water supply, light source and a ventilation device. The state of the animals was assessed with respect to their motor activity. The flight experiment was preceded by a number of preparatory runs and testinns that were completed with an end-to-end experiment in a biosatellite mockup. The flight experiment was paralleled by the ground-based synchroneous experiment which simulated almost entirely the flight profile. For each experiment rats were selected and trained during a month's observation. Postflight rats were exposed to clinical, physiological, morphological, cytochemical and biochemical investigations. Tissue examinations were performed on the 2nd-3rd day (20 rats) and 26-27th day (12 rats) after flight. Four rats were kept to study remote aftereffects.

On the basis of a morphological examination of 27 rats that made a space flight and were sacrificed on the 1st-2nd and 26-27th days postflight, it has been shown that the 22-d space flight has produced no significant changes in the structural organization of vital organs of the animals. However, a space flight exposure is not indifferent for animals and leads to the development of morphologically visible changes in individual organs and systems (musculo-skeletal system, hemopoietic organs, hypothalamic-pituitary-adrenal system, renal juxtaglomerular system). The detected changes are reversible, nonspecific, and develop in animals exposed to ground-based hypokinetic and other stress experiments.