Effect of physical loads on lipid and carbohydrate metabolic indices in hypokinesis

Experiments on 140 white rats kept under hypokinetic conditions for 15, 30, 60 and 90 days showed a significant decrease of the glycogen content in the liver and skeletal muscles, acceleration of lipolysis in the adipose tissue, progressive increase of the content of nonesterified fatty acids, ketone bodies and cholesterol in the blood, decrease of the content of total lipids and increase of the cholesterol content in the skeletal muscles and liver. Hypokinetic rats exposed to exercises (swimming) also exhibited changes in carbohydrate and lipid metabolism; however the content of ketone bodies in the blood increased a little, the glycogen content in tissues decreased to a lesser extent, the cholesterol level in the and skeletal muscles increased only on the 15th day, remained at the control level at later stages and even decreased in the skeletal muscles. Thus, during an exposure to hypokinesia and its combination with exercises the role of lipids on the energy balance of the animal body increases. Exercises facilitate better utilization of lipids, thus delaying adverse effects of hypokinesia.     

Effect of hypokinesia on human nutritional status

In three series of experiments of 120, 49 and 180 days in duration 36 test subjects were exposed to clinostatic and antiorthostatic hypokinesia. Human requirements for various nutrients were defined under hypokinetic conditions. It was demonstrated that during bed rest exercises together with adequate nutrition and after bed rest certain nutrients can serve as efficient countermeasures against metabolic changes.     

Energy metabolism in the erythrocytes of humans exposed to anti-orthostatic hypokinesia

Energy metabolism in red blood cells of men exposed to antiorthostatic hypokinesia (-8 degrees) was investigated. It was found that during this exposure erythrocytes synthesized organic phosphates such as diphosphoglyceric acid (2,3-DPG), ATP and ADP that were similar in terms of their effect on hemoglobin affinity for oxygen. On hypokinesia day 6, when the oxygen concentration in the erythrocyte environment increased, the content of the above phosphates also grew. It can therefore be concluded that glucose metabolism in erythrocytes of test subjects exposed to antiorthostatic hypokinesia is implemented via enhanced interaction between glycolytic and pentose-phosphate pathways.     

Changes in the mitochondrial oxidative enzyme activity in the skeletal muscles od rats during the recovery period after hypokinesia of varying duration

Enzyme activity was measured in 164 white rats exposed to hypokinesia of varying duration. NAD- and NADP-dependent isocitrate dehydrogenases (ICDH) decreased on hypokinesia day 7 and returned to normal on recovery days 4-5. Their enzyme activity was diminished on hypokinesia day 15. NAD- and NADP-dependent ICDH returned to normal on recovery days 11 and 7, respectively. Activity of alpha-ketoglutarate dehydrogenase (KGDH) and succinate dehydrogenase (SDH) decreased immediately after hypokinesia and remained lowered till day 18. Activity of pyruvate dehydrogenase (PDH) was decreased on recovery days 1-3 and increased on days 9-17. After 30-day hypokinesia PDH activity was lower than normal on recovery days 2-14. 30-day hypokinesia led to reduction of ICDH, KGDH, and SDH. NADP-dependent ICDH returned to normal on recovery day 12 and other enzymes during the third week of readaptation. These results suggest that during recovery the enzymes that are responsible for energy metabolism restoration are first to return to normal.     

Individual characteristics of water-mineral metabolism during 120-day head-down tilt hypokinesia and the effectiveness of prophylactic measures

Sodium balance and circulating plasma, intracellular, extracellular and interstitial fluid volumes were measured in the test subjects exposed for 120 days to head-down tilt at -5 degrees. The large scatter of the above parameters was associated with individual variations and with the use of different countermeasures against demineralization (exercise and drugs-xydiphone and glucamak). The effect of the countermeasures was different both in qualitative and quantitative terms. It appears that the target of their action was different. The best prophylactic effect was seen when exercise and drugs were used in combination. These findings suggest that individual variations of fluid-electrolyte metabolism during prolonged hypokinesia are related to the different capacity of tissues for water and electrolytes.     

Immunologic mechanisms of regulating calcium metabolism in human bone tissue (production of osteoclast-activating factor) during long-term anti-orthostatic hypokinesia

During 370 days 10 healthy male subjects were exposed to antiorthostatic hypokinesia. The exposure enhanced the production of the osteoclast-activating factor (OAF) by blood mononuclear cells. The enhancement began after the 2nd month of hypokinesia and continued to increase thereafter. The index of resorption was: prior to hypokinesia--1.15 +/- 0.156, 8 months after onset--2.05 +/- 0.129, and 11.5 months after onset--2.37 +/- 0.296, the upper normal limit being 1.54. The changes were correlated with a greater amount of active T-lymphocytes in blood and a progressive increase of calcium negative balance. This investigation lends support to the previously formulated hypothesis (I. V. Konstantinova, 1986) that immunological mechanisms associated with the OAF production contribute to calcium metabolism disorders in human bone during prolonged space flights.     

Effect of hypokinesia on the osteogenetic and hematopoietic functions of the bone marrow in mice. The ectopic bone model

Using heterotrophic transplantation of syngenic bone marrow under the renal capsule, the effect of hypokinesia on osteogenic and hemopoietic cells-precursors as well as on de novo formed bone marrow was investigated. Altogether 16 experiments were performed, employing 260 recipients and 200 donors in two modifications: 1) bone marrow from animals exposed to hypokinesia for 3 days or 3 weeks (stage I or II of the general adaptation syndrome) was implanted to intact mice; 2) recipients who 5 to 7 day before exposure were implanted with bone marrow from intact donors were hypokinetic for 3 weeks. It was found that determined bone marrow precursors of osteogenic tissue as well as cells transferring hemopoietic microenvironment remained insensitive to hypokinesia. Three-week hypokinesia produced noticeable inhibition of osteogenesis and hemopoiesis. It is concluded that the stress-reaction plays the leading role in the changes that develop in hypokinetic mice.     

Status of alpha 1-adrenergic regulation of stroke volume during hypokinesia in the rat

The positive effect of phenylephrine (PE) on stroke volume (SV) was 3 to 5 times weaker in the rats exposed to hypokinesia for 30 days as compared to the controls. After obsidan blockade of beta-adrenoreceptors SV increased in both groups and the intergroup differences in the PE effect remained significant but less pronounced. This can be attributed to a greater effectiveness of PE after obsidan administration during hypokinesia. Correlation analysis showed that the weak effects of PE on SV were potentiated by obsidan (potentiation was the stronger the weaker the effects) while the distinct effects were on the contrary inhibited. This demonstrates the synergy--antagonism relationships in the PE and obsidan interaction and seems to indicate that the common site of their action is alpha 1-adrenoreceptors. After phentolamine injections the PE effect on SV was not found. In this situation SV decreased; the SV decrease as well as its increase under the action of obsidan was less significant in the hypokinetic than in the control rats. The above investigation suggests that the activity of alpha 1-adrenoreceptors involved in the actualization of positive effects of agonists on SV is considerably lower during hypokinesia.     

Lipid peroxidation in the human blood during a 120-day period of anti-orthostatic hypokinesia

Time-course variations in the accumulation of endogenous products of lipid peroxidation and the state of antioxidative enzymes--superoxide dismutase and catalase--in blood of men exposed to antiorthostatic hypokinesia (-4.5 degrees) for 120 days were investigated. It was found that bed rest led to stimulation of lipid peroxidation which was measured as increased concentrations of lipid hydroperoxides and final products of lipid peroxidation in blood. Vitamin E and drugs with a specific metabolic action produced a normalizing effect on the content of products of lipid oxidative destruction. Special exercise regimens had a similar but less significant effect.     

Metabolic aspects of readaptation after hypokinesia (based on experimental results with animals)

This review discusses changes in protein, carbohydrate and lipid metabolism of animals during their readaptation after exposure to hypokinesia of varying duration. It is concluded that at an early stage of readaptation anabolic reactions aimed at the recovery of the bulk of active muscle proteins and the amount of energy substrates are predominant. In this situation the synthesis of lipids and carbohydrates is prevailing over their utilization. It is postulated that during readaptation amino acids are used more actively to make up for energy expenditures, gluconeogenesis and lipid synthesis. In the course of readaptation wave-like metabolic changes occur, being sometimes greater than during hypokinesia.     

Dynamics of several indices of carbohydrate and lipid metabolism during the period of readaptation after prolonged restriction of movement

Eighty-seven white rats were exposed to prolonged hypokinesia. On 90th hypokinesia day the content of cholesterol, free fatty acids and acetone bodies increased and the content of sugar and triglycerides decreased in blood, the content of glycogen decreased and the content of cholesterol increased in liver and skeletal muscles. On the 15th day after exposure most parameters returned to normal. However, glucose-6-phosphate dehydrogenase in liver and adipose tissue increased and remained elevated till recovery day 60. On the 30th recovery day the changes were similar to those during hypokinesia. On the 90th recovery day the content of triglycerides, cholesterol and acetone bodies in blood grew and the content of triglycerides and glycogen in muscles increased.     

Hormonal reaction of steroid-producing glands of female Papio to long-term hypokinesia

The endocrine function of steroid-producing glands of hamadryas baboon females exposed to 28-day clinostatic hypokinesia at different stages of the menstrual cycle was investigated. The adrenocortical response to hypokinesia developed in two phases: early stimulation was followed by inhibition of the adrenocortical activity which persisted during the subsequent period of hypokinesia and two weeks after exposure. The degree and duration of the activation effect of hypokinesia were determined by the initial phase of the menstrual cycle: the adrenocortical response during the follicular phase was higher than during the luteal phase. The hormonal function of ovaries was inhibited under the action of hypokinesia. The ovarian response was dependent on the initial phase of the menstrual cycle. Exposure to hypokinesia that began in the follicular phase resulted in a drastic reduction of estradiol while that started at the luteal phase led to a significant decline of progesterone. Monotonously low secretion of ovarian steroids was combined with desynchronosis of their circadian rhythms. Disorders in the function of steroid-producing glands during hypokinesia were transient.     

Role of active vitamin D3 metabolites in regulating calcium metabolism in rats during hypokinesia

The rats exposed to prolonged hypokinesia showed hypocalciemia, lower PTH and higher calcitonin concentrations in the serum, decreased calcium absorption in the small intestine, and a trend toward nephro- and arteriocalcinosis. Prophylactic administration of 24,25-hydroxy D3. 1,25-hydroxy D3 and their combinations enhanced calcium absorption and alleviated hypocalciemia. The changes in the hormonal regulation of calcium homeostasis can be viewed as a factor responsible for calcium metabolic disorders associated with hypokinesia.     

Morphologic and biochemical study of the functional state of the adrenal cortex in the rat during prolonged hypokinesia

Female rats exposed to 3-month hypokinesia were used to study adrenal morphology and plasma corticosterone. Prolonged hypokinesia (60-90 days) led to a dissociation between adrenal hypertrophy and lower corticosterone content in plasma. During hypokinesia rats were also exposed to an additional stress-effect, i.e. 5-hour immobilization. This approach showed that in the course of 90-day hypokinesia the adrenal cortex retained its ability to react to an acute stress by an enhanced corticosteroid secretion. Moreover, in response to stress-effects of identical strength and duration the experimental adrenals produced more corticosterone than the controls with no structural rearrangement or de-lipoidization.     

Dynamics of immobilization-induced osteoporosis in rats

Wistar male rats weighing 250-270 g were exposed to hypokinesia for 7, 15, 35 or 60 days. Spongy bone of the metaphysis of long bones, vertebral body, breast bone and iliac bone were examined histomorphometrically. It was found that during hypokinesia osteoporosis developed in two stages: Stage 1 (from hypokinesia day 1 to day 15) was characterized by a drastic bone mass loss due to stress-effects (steroid osteopenia) and Stage 2 (from hypokinesia day 15 to the end) was characterized by adaptive changes which included steady-state development and transition to a lower functional level (immobilization osteoporosis).     

Features of humoral regulation of metabolism during modelling of space flight factors

Hormonal regulation of metabolism was investigated in test subjects of three age groups: group 1 included test subjects of 41-50 years old, group 2 test subjects of 50-57 years old, and group 3 test subjects of 26-33 years old. Test subjects from groups 1 and 2 were exposed to head down tilt (-8 degrees) as well as linear acceleration of 3 GZ for 1 min and exercises of 450-1050 kgm before and after the tilt test. Group 3 test subjects were exposed to neuro-emotional stress before, during and after the head-down test. Exposure to head-down tilt, acceleration and exercises caused adaptive changes in humoral regulation of metabolism in the test subjects of groups 1 and 2. Food supplements given to group 3 test subjects produced a normalizing effect on humoral regulation of metabolism.     

Lipid peroxidation in tissues of rats exposed to head-down tilt, exercise or immobilization stress

Lipid peroxidation in tissues of rats exposed to antiorthostatic hypokinesia (-15 degrees) for 60 days, heavy-load exercise (swimming) and 2-hour immobilization was investigated polarographically. Antiorthostatic hypokinesia produced activation of free-radical lipid peroxidation in skeletal muscles, myocardium and plasma which reached a peak on hypokinesia day 3 and remained elevated by day 60. Exercise and immobilization applied during hypokinesia led to an accumulation of endogenous lipid peroxidation products in skeletal muscles and in the heart, although in a lesser degree. It is postulated that during hypokinesia lipid peroxidation is most probably activated due to the following factors: increased activity of the hormonal component of the sympathicoadrenal system, accumulation of excessive quantities of free fatty acids, and reduced activity of anti-oxidant enzymes.     

Effect of accelerations, hypergravity and hypokinesia on protein metabolism in Japanese quail. I. Effect on muscle composition]

The effect of hypokinesia, hypergravity achieved by centrifugation and additional weight load on the content and composition of proteins and nucleic acids in the chest and pelvic muscles of four groups of quails (Coturnix coturnix japonica) was studied. The first group was used as controls, the second included hypokinetic birds, the third was made of birds with an additional weight load (the load was a double weight of the animal) and the fourth group included birds exposed to acceleration of 3 g. The birds were exposed to the above effects for 1 to 6 hours during 8 days. They were given identical food through forced feeding. The content of total proteins, sarcoplasmatic proteins, DNA and RNA, cholesterol and esterified fatty acids was measured in chest and pelvic muscles. The composition of total lipids was examined in pelvic muscles. The level of corticosterone was determined in the blood plasma. The above experimental variants made it possible to discriminate individual contributions of acceleration, additional weight load and hypo-inesia to the effect. Weight load and acceleration decreased and hypokinesia increased the content of total proteins in the pelvic muscles. During an exposure to acceleration and hypokinesia the content and the portion of sarcoplasmatic proteins decreased and during an exposure to weight load increased significantly. Acceleration did not exert a significant effect on the RNA and DNA content in muscles. The content of esterified fatty acids increased under the influence of acceleration and hypokinesia and decreased significantly under the influence of additional weight.     

Tolerance of functional and exercise tests during 1-year antiorthostatic hypokinesia

During 370 days 9 healthy young volunteers were exposed to antiorthostatic hypokinesia. Group A consisting of 4 subjects performed exercises similar to those regularly made by Mir crewmembers and Group B consisting of 5 subjects did not exercise for 120 days and then performed experimental exercise regimens. It was demonstrated that the health status of men long exposed to head-down tilting can be controlled with the aid of various countermeasures. As a result of the exposure, orthostatic and exercise tolerance diminished. In view of the fact that the changes observed were more pronounced in the Group B subjects, it can be concluded that the countermeasures used were more effective in Group A subjects.     

Concentration of collagen, lipids and glycogen in the skeletal muscles of the rat during the recovery period after 15 and 30 days of hypokinesia

On the 15th hypokinetic day carcass mass, glycogen and lipid content in skeletal muscles decreased while collagen content increased. The content of collagen returned to the norm by the 7th day of the recovery period. By that time the glycogen content increased significantly and a week later decreased noticeably. The content of total lipids and triglycerides was higher than the baseline level on the 15th and 30th days of the recovery period. On hypokinesia day 30 carcass mass and glycogen content decreased while collagen content increased. After 30-day hypokinesia glycogen was significantly increased on the 7th day and returned to the norm by the 60th day of the recovery period. Lipid content was elevated only on the 7th day of the recovery period, collagen content returned to the norm on the 15th day of the recovery period. Following 15- and 30-day hypokinesia carcass mass returned to the baseline level by the 30th day of the recovery period.