Physiological Cost of Physical Exercise and Mitochondrial Volume in Working Muscles of Subjects Exposed to Long-Term Hypokinesia: Effects of Local Resistance Exercise

The results of changes in the physiological cost of 30-min submaximal aerobic bicycle ergometric exercise and characteristics of the mitochondrial apparatus of m. vastus lateralis were assessed comparatively during 120-day (–6°) antiorthostatic hypokinesia either without prophylactic measures or with low-intensity resistance exercise training for 60 days using a Penguin exercise suit. Hypokinesia was accompanied by an increase in the working heart rate and lactate accumulation in the blood during the test exercise, as well as by a decrease in the myofibril size and the volume density of mitochondria in the m. vastus lateralis fibers. The patterns of dynamic changes in the lactate concentration in the blood during exercise training and in the volume density of central mitochondria were found to be similar. A correlation between the rate of lactate accumulation in the blood during the test exercise and the volume density of mitochondria in the working muscle appeared after long-term (60 days) exposure to hypokinesia. The use of the Penguin exercise suit in dynamic mode during prolonged (60-day) exposure to hypokinesia completely prevented the following effects: atrophy of slow-type fibers, a decrease in the volume density of central mitochondria, and an increase in the level of lactate accumulation in the blood under conditions of a standard submaximal aerobic exercise load. The correlation links between the oxidative potential of working muscle and the energy supply of muscular work are discussed.     

Dynamics of oxidation stress markers during long-term antiorthostatic hypokinesia: A retrospective study

Nine volunteers aged 27 to 42 participated in an experiment with 370-day antiorthostatic hypokinesia at–5°C, and their blood serum samples were tested for the concentrations of lipid peroxidation (LPO) derivatives, including diene conjugates (DCs), malonic dialdehyde (MDA), and Schiff bases (SBs), and indices of the antioxidant defense system, including the tocopherol (TP) concentration and total antioxidant activity (AOA). The subjects were divided into two groups, which differed in physical training regimen and prophylaxis measures. Initial LPO steps were inhibited in both of the groups by 54–73% from day 50, while the level of SBs, which are final LPO products, decreased by 50–61% by day 230 and remained much the same up to the end of the experiment. The MDA and SB concentrations decreased by a factor of 1.6–2.3 during recovery. Total AOA decreased as an aftereffect during recovery to a level far lower than physiologically normal. Based on the significant inhibition of free-radical LPO throughout the experiment, long-term adaptation to simulated hypogravity was accompanied by a pronounced decrease in biological oxidation and caused severe stress. Substantial long-term readaptation stress developed during recovery after 370-day antiorthostatic hypokinesia, as was evident from the facts that the LPO activity was almost halved, TP concentration significantly increased, and the functional reserves of water-soluble antioxidants were exhausted. Lack of LPO activation was assumed to reflect adequate compensation in the subjects.     

Cardiovascular Function in Humans Using Thigh Cuffs during Seven Days of Simulated Microgravity

Data are summarized on changes in the human cardiovascular system associated with the use of cuffs during seven days of antiorthostatic hypokinesia simulating weightlessness. Eight subjects participated in two series of experiments, of which one was carried out with and the other (the control) without cuffs wrapped snugly around the upper third of the thighs. The parameters of the systemic hemodynamics, the cardiac function, and the hemodynamics of the cervicocephalic region and the lower limbs recorded under control and experimental conditions were analyzed. Without cuffs, changes in the hemodynamics during antiorthostatic hypokinesia were caused by displacement of body fluids in the cranial direction. The subjects responded favorably to the use of cuffs during antiorthostatic hypokinesia: most of their hemodynamic parameters remained at the baseline level, and signs of venous stasis in the cervicocephalic region were alleviated. Although the leg veins were distended in subjects wearing thigh cuffs during antiorthostatic hypokinesia, no pathological changes in the veins were detected during or after the experiment. Cuff usage during antiorthostatic hypokinesia lasting for seven days did not produce a cumulative effect on the cardiovascular system. These results justify the use of thigh cuffs in the initial period of adaptation to simulated or real weightlessness.     

Changes in metabolic processes in humans during a 120-day antiorthostatic hypokinesia

The activities of organ- and tissue-specific diagnostically significant enzymes, including aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, total and prostatic acid phosphatase, glutamate dehydrogenase, choline esterase, amylase, lactate dehydrogenase, oxybutyrate dehydrogenase, and creatin phosphokinase (muscular and cardiac isoenzymes), as well as the concentrations of total cholesterol and the cholesterol of high- and low-density lipoproteins, the ratios of their concentrations, and the level of triglycerides, were studied during an experiment with 120-day antiorthostatic (?7°) hypokinesia (ANOH) in the blood of six volunteers (men, 21 to 36 years old). In addition, the indices of lipid peroxidation (LPO) and antioxidant activity were determined, including the concentrations of diene conjugates, malonic dialdehyde, Schiff bases and tocopherol, and the total antioxidant activity. It was found that a 120-day ANOH in this experiment did not result in the formation of deep metabolic shifts accompanied by unfavorable changes in organs and tissues. The changes in cholesterol metabolism during hypokinesia were expressed in the redistribution of cholesterol fractions with the dominance of atherogenic forms and a higher risk of atherogenesis. All of the observed metabolic changes were easily reversible and eliminated during the first month of the recovery period. No signs of a higher intensity of free-radical processes were observed during any of the examination periods due to activation of the antioxidant defense system.     

Study of Temperature Homeostasis in Real and Simulated Weightlessness

The analysis of the temperature (T) reaction of the body of healthy humans was carried out using the results of investigations with the thermometry technique under antiorthostatic hypokinesia (ANOH) (38 males in the studies of 14- to 49-day duration, eight females, 120 days), isolation in a regenerated gas environment (six males, 90 to 135 days), suit immersion (46 males, three to 72 days), and space flight (three males, 12 to 174 days) conditions. Using digital thermal thermometers, the morning and evening T values, namely, oral, rectal, and at 9 to 11 points on the body surface, were recorded at rest (under the ANOH and isolation conditions, bed rest regimen). The weighed average body and skin T, the chest–foot, core–membrane T-gradients, etc. were calculated. The flight pattern of the T-parameters of three astronauts preliminarily investigated under suit immersion conditions is given. The results of our studies show that, under real weightlessness and (partially) its terrestrial simulation conditions, the effectiveness of the thermoregulation mechanisms may decrease due to the changes noted at each of the main stages of heat exchange (metabolic heat production, transfer, and emission), up to the development of desynchronosis. The differences in individual adaptive shifts in the subjects differing in the level of thermal sensitivity, their interrelationship with the reactions of water–electrolyte metabolism, hormonal control, resting energy expenditure, and physical working capacity call for further natural and experimental studies.     

Reaction of striated fibers of human skeletal muscles to long-term anti-orthostatic hypokinesia

Eight men have been kept under a strict bed rest. The lower end of the bed has been elevated by 6 degrees. During the whole effect of the antiorthostatic hypokinesia (AOH) in biopsy of the skeletal muscle tissue no gross morphological changes and essential changes in relation of the muscle fiber (MF) types have been found. On the 120th day of AOH without application of any physical loading concentration of RNA, protein metabolism, glycogen, activity of the energetic metabolism enzymes, MF size decrease. Both contractile and energetic apparatus suffers essentially. This demonstrates certain atrophic processes in both types of the MF. Physical loading against the background of AOH, on the 120th day, prevents development of the atrophic processes in MF. This is demonstrated as maintenance of certain metabolic level and less pronounced changes of ultrastructure. On the 360th day of the experiment in the group without any loading, an essential atrophy of MF, a noticeable++ decrease in metabolism are observed. In the test group against the background of AOH the changes in the biopsy fibers are less pronounced and not so uniform. Application of physical loadings contributes to the development of certain adaptive reactions; their positive effect to the skeletal muscle fiber morphology depends on the structural background, against which it acts and their intensity. The earlier the load begins to act and the higher its intensity, the more pronounced is the delay in development of profound atrophic changes.     

Dynamics of the glycemic profile in women in long-term antiorthostatic hypokinesia

The dynamics of the glycemic curve profile was investigated in 8 healthy women during performance of the glucose tolerance test (GТТ) in 120-day antiorthostatic hypokinesia (–6°) (АNОH) simulating the effects of weightlessness. Glycemic profiles were characterized by more marked hyperglycemic response at 30 min of GТТ in the first month of stay under ANOH conditions and had a flattened appearance three months later. Glycemic profiles characteristic of delayed restoration of the blood glucose concentration appeared in the fourth month, which persisted over the first week after the end of АNОH. The glycemic profile changes developed against the background of the signs of progressive congestion of blood in the venous system of the abdominal cavity. The expansion of diameters of the main veins of the abdominal cavity was noted at the beginning of АNОH; an increase in the size of the organs and the signs of expansion of venous plexuses at the site of portocaval anastomoses, after three months; the occurrence of the signs of transudation and free fluid in the abdominal cavity was revealed at the end of hypokinesia. The countermeasures against hypodynamia did not prevent transformation of the glycemic profile nor did they influence the progression of blood flow congestion in the venous system of the abdominal cavity whose features determined the character changes in the glycemic profile in different periods of ANOH.     

Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after addition of succinate into diet

The intensity of cell respiration of the rat m. soleus, gastrocnemius c.m., and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the unloading. This may be associated with the transition to the glycolytic energy pathway due to a decrease in the EMG activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.     

The physical work capacity of the body in experiments with the combined action of hypokinesia and radiation]

After combined exposures to hypokinesia and radiation, hybrid CBA x C57BL mice of the first generation showed a drop in their working capacity as estimated by the rate of swimming through a limited distance. It was found that hypokinesia was a sufficiently strong stressor, no less affecting the working capacity than ionizing radiation in LD50. There was no summation in effects of these irritants with respect to the drop in working capacity.     

Dehydrogenase activity in skeletal muscles of rats after long-term exposure to weightlessness

Malate- and isocytratedehydrogenase activity in mitochondrial and cytoplasmic fractions and lactate dehydrogenase activity in hindlimb muscles have been studied at different stages after 18.5-day flight on a biosatellite "Cosmos-1129" and after 20-day hypokinesia. A decrease in dehydrogenase activity has been found on the first postflight day. The enzyme activities returned to the control values in mitochondria, and in the cytoplasm they were greater by day 6 postflight. It was concluded that hypokinesia did not reveal all the effects of microgravity on the whole system but some enzyme alterations in the muscle resembled those observed during the flight. The effects may be caused by the inhibition of both aerobic and anaerobic metabolic pathways under the effect of microgravity.     

Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after dietary succinate supplementation

The intensity of cell respiration of the rat m. soleus, m. gastrocnemius c.m. and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the discharge. This may be associated with the transition to the glycolytic energy path due to a decrease in the EMG-activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.     

Adaptation of the Human Body to Simulated Weightlessness: Clinical Studies

Problems of adaptation of functional systems of the human body to conditions of continuous weightlessness are considered (prolonged stay under conditions of antiorthostatic hypokinesia and in an immersion medium). It was revealed that, during adaptation to these conditions, polymorphic clinicofunctional disorders develop, transforming into clinicophysiological syndromes, the most frequently observed being autonomic vascular malfunction, asthenoneurotic syndrome, detraining of the blood circulatory system, trophic and neuromuscular disorders, statokinetic syndrome, pain syndrome, and metabolic and hormonal disorders. The severity of the specified disorders and the duration of the recovery period depend on the duration of hypokinesia and the intensity and regularity of application of preventive measures during hypokinesia. The most probable pathophysiological mechanisms of adverse effects of continuous hypokinesia (maladaptation) on functional systems of the human body are described.     

The phasic structure of early disorders of functional capacity following irradiation in rats

In experiments with rats it was shown that an early decrease in physical efficiency after irradiation involves some partially mutually superimposed phases. Phases of excitation, hypokinesia and neurological disorders are identified in early transient inefficiency followed by phases of an early transient diminution of efficiency and a reversible disturbance of the accomplishment of the known operations. Simultaneously, there is a phase of an irreversible decrease of the informational capacity of CNS as well as the tolerance to early transient in efficiency upon repeated exposure.     

Mitotic activity of the lymphocytes of the thymus cortex in hypokinesia during the period of readaptation

The changes in the weight and mitotic index were studied in the cortex of the thymus of Wistar rats during 10-day hypokinesia and 10-day readaptation (restoration). 24 hours after immobilization of the animals the mitotic index was 2 times as lower. No complete readaptation was attained during 10-day hypokinesia. No readaptation was attained during 10-day hypokinesia. In readaptation the stage of secondary stress was found (the mitotic index was 3.5 times as reduced), the stage of genuine restoration being revealed after 10 days.     

Systemic and regional hemodynamics in conscious rats during 24-hour antiorthostatic posture

The systemic and regional hemodynamics during antiorthostatic hypokinesia were studied in male Wistar rats using the radioactive microsphere technique. The animals were hanged up by the tail with the head tilted down (30 degrees) and were able to exercise using only front limbs. Twenty four hours long exposure to antiorthostasis induced significant changes in systemic hemodynamics as well as in regional blood flow in skeletal muscles, spleen, liver and pancreas. Antiorthostasis induced blood flow changes in lungs, heart and brain were less pronounced.     

Efficacy of the Combined Use of Negative Pressure on the Lower Part of the Body and Negative-Pressure Respiration under Simulated Microgravity

The efficacies of the standard procedure for application of negative pressure on the lower part of the body (NPLB) and a combination of NPLB and negative-pressure respiration (NPR) during a simulated last stage of a spaceflight under conditions of antiorthostatic hypokinesia (ANOH, –6°) and isolation for 7 days have been compared in the course of three series of tests involving six volunteers in an EU-100 pressurized chamber. After the end of the 7-day ANOH and isolation, episodes of orthostatic disorders were observed in all six subjects in the first series of tests (the control series) and in four subjects in the second series (NPLB). In the third series (NPLB + NPR), orthostatic disorders, if any, were slight. Two main conclusions have been made. First, ANOH combined with isolation in a small chamber may be used to simulate the effects of the combined factors of spaceflight on humans in order to obtain model gravitational circulatory disorders. Second, the combined use of NPLB + NPR under these conditions may be effective for the prevention of orthostatic circulatory disorders in humans.     

Adaptive Responses of Secretory Cardiomyocytes of the Right Atrium during Simulation of Microgravity Effects by Long-Term and Repeated Antiorthostatic Tail Suspension of Rats

Reactive changes in right atrial cardiomyocytes during antiorthostatic tail suspension of rats, which is commonly used to simulate effects of microgravity, have been studied by electron microscopy and morphometry. A 14-day tail suspension proved to increase contractile and secretory activities of cardiomyocytes. At the same time, signs of depleted activity are observed in some cells. Prolongation of the experiment to 30 days leads to development of adaptive compensatory responses and increases their secretory capacity. A 30-day rest in the normal orthostatic position does not completely restores the structure and functioning of cardiomyocytes and leads to accumulation of internal secretion in them. A repeated 14-day tail suspension to a certain extent facilitates cardiomyocyte adaptation to altered conditions as compared to a single exposure; apparently, secretion release decreases, while its production is activated.     

The effect of long-term bed-rest head-down-tilt hypokinesia on the functional properties of the human neuromuscular apparatus]

An influence of 120-days antiorthostatic (-6 degrees) hypokinesia (ANOH) on the functional properties of human m. triceps surae (TS) was investigated. After ANOH the maximal force and the maximal voluntary contraction of TS decreased on the average by 45.5% and 33.7%, respectively, and the maximal twitch response force--by 36.7% (P < 0.05-0.01). The value of force deficit increased on the average by 60.2% (P < 0.001), while a relative increase of the TS force contraction decreased in response to pair irritation (P < 0.05-0.01) as well as the velocity properties of TS after ANOH (P < 0.05-0.001). The rate of absolute (c.u.) tension development fell significantly in response to electrical nerve irritation and during voluntary contraction, while the force-velocity muscle properties according to relative (%) parameters remained unchanged. The fatiguability index of TS constituted the average 0.61 +/- 0.02 after ANOH as against 0.80 +/- 0.03 prior to it (P < 0.05). It is postulated the alterations of contractile properties of TS are due both to atrophic processes, muscle length change, condition of sarcoplasmic reticulum and to changes in the state of the central nervous system.     

Effect of hypokinesia on nucleic acid and protein metabolism in the lymphoid organs of rats

Metabolism of nucleic acids and protein by lymphoid cells of the rat spleen and thymus was studied under conditions of 22-day hypokinesia. It was shown that in the course of hypokinesia the loss of cellular mass by the spleen and thymus was associated with varied biochemical changes in the remaining lymphoid cells. The thymocytes showed a significant activation of nucleic acid and protein biosynthesis. Meanwhile in spleen lymphocytes, DNA and RNA metabolism was inhibited with no appreciable changes in protein metabolism. Potential mechanisms of changes in metabolism of thymus and spleen lymphocytes under long-term hypokinesia are discussed.     

Long-term antiorthostatic hypokinesia stimulates storage of osmotically inactive sodium in the human body

Changes in the water and sodium balances and in the states of the fluid compartments of the human body observed in experiments performed with healthy subjects exposed to long-term (120 days) antiorthostatic hypokinesia (ANOH) were analyzed. A hypothesis was suggested that the normal dietary consumption of sodium could be associated with the accumulation of osmotically inactive sodium in the body of a healthy person (independently of changes in the total water content). The results agree with the assumption that considerable amounts of osmotically inactive sodium may be stored in the human body. This hypothesis was confirmed by the inversion of the correlation between the cumulative sodium balance and the total water content of the body found both in the group-averaged data and in individual data. This nonsmotic sodium accumulation may take place not only during deviations from its normal consumption, but also during its regular dietary supply. Accumulation of sodium in these stores and its depletion are not associated with any significant changes in the volumes of body fluids. Infradian rhythmic changes in the sodium balance observed in some subjects exposed to the long-term ANOH, which were not caused by any periodic external influences, indicated the existence of a specific mechanism regulating the sodium content of the body. This mechanism must be significantly more inert and less precise than the fast regulation of the volume, osmolality, and ionic composition of extracellular fluids.