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After humans and animals have been in conditions of real and modeled weightlessness, the most marked changes are seen in the "slow" tonic muscles, particularly soleus. Studies of the effects of weightlessness and movement restriction on the soleus muscle in monkeys demonstrated significant reductions in the sizes of slow and rapid fibers due mainly to the actions of real weightlessness (rather than movement restriction in the space capsule). Protein loss in soleus muscle fibers in monkeys following space flight was more marked than loss of other components, including water. The level of atrophy of soleus muscle fibers in these conditions was greater than the decrease in the number of capillaries. Succinate dehydrogenase activity in soleus muscle fibers decreased proportionally to the reduction in fiber size.

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Monkeys subjected to space flight were found to have significant decreases in the sizes of slow and rapid fibers in the vastus lateralis muscle, due not only to weightlessness but also, to some extent, to restriction of movement activity within the capsule. The quantity of total protein in muscle fibers did not decrease. The respiratory peak in the pool of vastus lateralis muscle fibers decreased after space flight, as did the activity of oxidative enzymes (particularly in rapid fibers of the vastus lateralis muscle).

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Monkeys developed a significant reduction in size of the m. vastus lateralis' fast and slow fibres, the amount of protein in them remaining the same.

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After staying in real and simulated weightlessness, the most obvious changes were recorded in the "slow" tonic muscles like m. soleus, the protein loss in the fibres being greater than the loss of other components, water included.

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The fiber size decline, alterations in fiber metabolic potential and increase of connective tissue component were shown in human m. vastus lateralis after short and long-duration space flights and in m.soleus and m.vastus lateralis after 120 day head down tilt bed rest. It is known from rat and monkey studies that the exposure to weightlessness leads to the most pronounced changes in postural muscles, e.g. m.soleus. It was shown that 17 day space flight induced significant decrease of fiber cross-sectional area and slow-to-fast fiber type transformation in human soleus. But in the cited work the fiber population under study was limited like in most single fiber technique analyses. The present study was purposed to investigate the structural and metabolic properties of soleus muscle in Russian cosmonauts exposed to 129-day space flight on board of the International Space Station.

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It had been hypothesized and recently shown that the exposure to gravitational unloading brought out to sufficient accumulation of Ca2+ in the myoplasm of soleus muscle fibers. Some authors believe that this dramatic Ca2+ accumulation induces the muscle protein degradation (including cytoskeletal proteins) by means of Ca 2(+)-activated proteases. For instance, the loss of giant sarcomeric cytoskeletal protein titin which is believed to determine the elasticity properties of muscle fibers, may contribute to the fiber stiffness decrease under unloading conditions. The study was designed to test the hypothesis suggesting that intracellular Ca2+ binding by means of EDTA administration would allow to attenuate hypogravity-induced atrophic changes including changes in myofibrillar proteins of skeletal muscle fibers.

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It is known that exposure to actual or simulated weightlessness is often accompanied by decreased muscle dynamic performance, and increased level of blood lactate accumulation. Decreased mitochondrial content found in fibers of the working muscles is considered to be one of the possible causes for those changes. Studies on oxidative potential of the muscle cell (i.e. capacity of the cell to oxidative energy production) under conditions of altered gravity have been carried out since late 70-ties. It was shown that the relatively short term spaceflight and hindlimb suspension induced significant decrease oxidative enzyme activities and mitochondrial volume density in rat fast muscle. However postural soleus muscle failed to exhibit similar changes, although the absolute mitochondrial content was found to be sufficiently lower after exposure to simulated microgravity. This phenomenon allowed to conclude that the pronounced soleus fiber atrophy masked the proportional absolute decrease in oxidative potential which failed to be revealed as subsequent changes in mitochondrial volume density and oxidative enzyme activity. It is also important, that biosatellite studies exposed considerable changes in mitochondria distribution pattern inside m. soleus fibers: volume density of mitochondria (and, correspondingly, activity of oxidative enzymes) increases (or does not change) in the center of fiber, and decreases at its periphery, in subsarcolemmal area. However the time course of mitochondrial alterations development (particularly during long-duration exposures to real or simulated microgravity) and some peculiarities of the mitochondria distribution were not described yet. Also, materials dealing with simultaneous time-course comparative analysis of mitochondrial characteristics and indices of physiological cost of submaximal exercise are very rare. The present paper is purposed to compare the data, obtained in several experimental studies, allowed to analyze the possible contribution of muscle mitochondria changes to changes in metabolic cost of submaximal exercise and the time-course dynamics of mitochondrial characteristics under conditions of actual or simulated gravitational unloading.

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Studies of m. vastus lateralis in Rhesus monkeys exposed to weightlessness on board of the Russian biosatellites showed the profound changes of the muscle structural and metabolic profile. It is known that exposure to head-down tilt berets (BR) induces the similar changes though not so pronounced. It is supposed that the artificial gravity application is one of the promising countermeasure means purposed to prevent from the unfavourable effects of exposure to weightlessness. The present work was aimed to study the effects of the artificial gravity on structural and metabolic characteristics of hind-limb muscle in monkeys exposed to BR. 11 monkeys were subjected to 30 day 6 head down tilt BR.5 animals of them (group BR + Gz) were exposed also to daily rotation on the centrifuge (1.4 G for 5-20 min), the other animals (BR) were under only pure BR during the study. In BR animals the m. vastus lateralis slow-twitch (ST) and fast-twitch (FT) fiber size decreased by 25.4% and 12.7% respectively. In group BR + Gz the ST and FT fiber cross-sectional area was reduced by 18.7% and 8.1% respectively. The area percentage of the connective tissue compartment in BR animals increased from 4.6% to 6.8%. Capillary per fibre ratio was reduced by 9.6% and 8.6% in BR and BR + Gz monkeys respectively. The less pronounced level of capillary reduction as compared to level of fibre size decrease led to the increase of the capillary density by 13% in BR group, and no change in BR + Gz one. No changes in succinate dehydrogenase (SDH) activity were revealed in fibres of BR animals (this phenomenon may be the consequence of the proportional decrease of the oxidative potential and fibre size). In BR + Gz monkeys the SDH activity were found to be significantly elevated by 22.2% and 28.6% in ST and FT fibres respectively. Thus the data obtained show that chronic application of Gz tends to diminish the intensity of structural and metabolic changes in skeletal muscles under simulated microgravity.

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Intensive muscle tension induces significant blood accumulation of enzymes and structural proteins of the muscle origin. Altered macromolecular permeability of the sarcolemma is attributed to integrity of sarcolemmal cytoskeleton, mainly to dystrophin-sarcoglycan (DSG) complex. It is known that intensive tension of the antigravity extensor muscles is observed under conditions of gravitational overloading. We assumed that acute exposure to hypergravity would lead to serum accumulation of creatine phosphokinase (CK) associated with considerably altered integrity of the dystrophin layer in fibers of extensor muscles.

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The dynamics of atrophy in the muscles-extensors of the leg and thigh during long-term hypokinesia was studied with the model of head-down tilt (HDT -6 degrees) in a series of two experiments (120 and 60 days in duration) with participation of men and women. Dynamics of the cross-sectional area of human muscular fibers was characterized by similar atrophy of the fast and slow fibers on the first stage of HDT. Later on, the size of fast fibers in m. soleus and m. gastrocnemius lateralis reached plateau whereas the size of slow fibers continued to diminish. These were only fast fibers that underwent further atrophy in locomotor m. vastus lateralis. A supposition can be made that the controversy between literature data on the character of atrophy of muscular fibers in experiments with human subjects and rodents is primarily linked with different rates of atrophy developed by muscles in various species; besides, investigators describe different stages of one process. Analysis of the benefit from preventive exercises for the muscular atrophy control during HDT indicated that locomotor (with loading restraint belts) and resistive exercises can preclude slow fibers atrophy under the conditions of hypokinesia.

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It was shown that changes in structural and metabolic indices of extensor muscles of the lower extremities were usually found in man after exposure to space flight or to bed rest. Similar changes were also observed in monkeys, space-flown on "Kosmos" biosatellites. Response to weightlessness and to restraint was found to be different in m. soleus and in m. vastus lateralis. Therefore, it is important to study structural and metabolic changes of m. vastus lateralis fibers under conditions of gravitational unloading in monkeys, who have motor apparatus similar to that of man, and are much more fruitful object of research. It is assumed that artificial gravity can serve as a countermeasure, aimed at diminishing effects of gravitational unloading. We have studied the effect of repeated gravity overloading, created by means of a centrifuge, on structural and metabolic indices of monkey m. vastus lateralis at the background of 30 day head down tilt bed rest (BR).

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The effect of microgravity and diminished motor activity on m. soleus fibers of rhesus monkeys was investigated. A significant size reduction of both slow- and fast-twitch fibers was found in the flight animals only. Also, total protein and capillary per fiber number were shown to decrease in the flight animals.

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The effect of microgravity on slow- and fast-twitch fibers of m. vastus lateralis of rhesus monkeys was investigated. After real flight, fibers of both types were reduced in size, whereas after simulated flight, only type I fibers tended to diminish. Oxidative potential decreased in type II fibers of both flight and control animals.

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There have been presented the results of studying the reactivity of leucocytes with respect to tuberculin and monspecific migration activity of leukocytes in the cosmonatus pre flight and after completion of orbital expeditions of various duration are presented. In some cosmonauts tuberculin rearranged migration of leukocytes. This may bear witness to activisation of the immunity system in response to the antigens which had been already familiar to test-subjects. Experimental data pointed to significant changes in leukocyte mobility in 12 out of 28 cosmonauts examined on days 1 and 7-14 of recovery after the first or repeated long-duration space missions indicating some functional disorders in the phagocytic link which may lead to a typical decline in human resistance to infections.

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Migration activity of the leukocytes featuring the functional state and metabolic activity of immunocompetent cells was studied. Migration of phagocyting cells was explored in 8 female test-subjects in the course of 120-day head-down bed rest and 3 male volunteers isolated in a hermetically sealed room over a similar period. Bed rest without use of preventive measures decreased significantly the migration activity of leukocytes; on the opposite, administration of the preventive measures by the bedrested subjects doubled the parameter. In the experiment with the long-term isolation the activity of leukocytes decreased significantly.

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Metabolism and structural/functional status of membrane of blood cells (erythrocytes, lymphocytes) were investigated in human subjects during simulation of MIR environment and operations, and postflight activities. Homeostasis of the blood count cells was assessed by the parameters of intercellular metabolism. Histochemical technique was used to evaluate the activity of mitochondrial enzymes succinate dehydrogenase and alpha-glycerphosphate dehydrogenase in lymphocytes. State of the erythrocyte membrane was judged about by the lipid and phospholipid spectra, activity of transport ATPase and shape of erythrocytes were determined with the electronscan microscopy. Adaptational shifts in erythrocyte metabolism were particularly marked on days 22 and 113 in the experiment, and day 1 of recovery. They appear to be associated with alterations on the membrane level. Therefore, simulation of a long-term MIR mission produces changes in cellular metabolism and status of cellular membranes concurrent to the readjustment of body controls due to, probably, shifts in the sympathoadrenal system. Destabilization of the cellular membrane could be also linked with plasmic factors, e.g. increases in bile acids, lysolecithin, Ca ions, etc., in consequence to changes in lipid metabolism and electrolyte status.

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