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Male rats of the Wistar strain were for 40 days exposed to hypokinesia and hypodynamia. After exposure bone biochemical, physical, chemical, morphological and strength parameters were investigated. Both simulation studies led to changes in calcium and phosphorus metabolism but the nature of bone changes was different. It is concluded that the efficacy of drugs used as countermeasures in animal simulation experiments should be assessed by both exposures, viz. small size cages and suspension, because they reproduce different mechanisms of potential bone lesions in microgravity. It is also inferred that various countermeasures should be used in combination to yield the best results.

Fluid-electrolyte metabolism and renal function of the crewmembers of the 185-day space flight were examined. Various changes in fluid-electrolyte metabolism and its regulation were seen in the Commander and Flight-Engineer. As most other crewmembers who performed similar flights, Cr showed fluid and sodium retention, whereas FE displayed higher than preflight sodium excretion in the urine. These differences were associated with individual variations of regional hemodynamics which modified the renin-angiotensin-aldosterone system in a different manner. Postflight both crewmembers showed a higher excretion of bivalent ions. The higher excretion of calcium was accompanied by a lower concentration of total and ionized calcium in the serum as well as by a lower concentration of PTH and calcitonin. The loading KC1 test made it possible to assess variations in potassium metabolism that occurred during flight. They included the inability of tissues to retain potassium due to atrophic processes which developed in the weightless state and due to the unloading of the musculoskeletal system.

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.

The diphosphonate effect on bones was studied in Wistar male rats weighing about 200 g. The rats were kept for 60 days in small-size cages where their motor activity was diminished. Every day the rats were given per os 0.3% solution of 1-hydroxy-ethylene-1,1-diphosphonate (HEDP) containing 9 mg/kg phosphorus. In the course of hypokinetic exposure the rats developed generalized osteoporosis. Histomorphometric measurements demonstrated that the drug did not prevent mineral losses from the tubular bones (humerus, femur). However, the drug led to a complete bone mass recovery in the pelvic and a partial recovery in the sternum. The drug also produced a preventive effect on the population of cells-precursors of osteogenesis the number of which decreases significantly during hypokinesia.

Using histomorphometric methods, the effect of diphosphonates (hydroxydimethylaminopropylene diphosphonic acid and hydroxyethylene diphosphonic acid) on the development of osteoporosis in spongy matter of tibia and vertebrae of the rats exposed to hypokinesia for 60 days was investigated. It was found that aminopropylene diphosphonic acid in the dose 6 mg phosphorus/kg/day prevented osteoporosis and caused an increase in the volume density and abnormal (cartilage rich and poorly ossified) spongy bone. By contrast, ethylene diphosphonic acid in the dose 9 mg phosphorus/kg/day did not prevent osteoporosis but reduced its severity.

Two groups of 5 healthy volunteers each were exposed for 7 days to: 1) group 1 to horizontal bed rest and 2) group 2 to head-down tilt at -6 degrees. The purpose of the study was to determine the effect of body position on fluid-electrolyte metabolism and renal function. During the control period (14 days), bed rest and the recovery period the consumption of fluids and mineral substances and their renal excretion were measured. The typical changes in fluid-electrolyte metabolism during head-down tilt developed faster than during horizontal bed rest. The fluid-electrolyte balance became negative in the course of the exposure and returned to normal during the recovery period. The group 2 subjects showed greater body weight losses due to both fluid and muscle mass losses.

Nine healthy test subjects, aged 25 to 44 years, were exposed to bed rest (at -5 degrees) for 120 days. Venous blood and 24-hour urine samples were used to measure Na, K, total and ionized Ca, Mg, total protein, protein fractions, creatinine, urea, uric acid, malate, isocitric and lactate dehydrogenases, aspartate and alanine aminotransferases, and creatine phosphokinase and its isoforms, acid and alkaline phosphatase and its isoenzymes. Prolonged exposure to head-down tilting resulted in a negative balance of fluid and electrolytes, lowered concentration of total protein and albumins, and an increased concentration of urea and creatinine, basic products of protein metabolism. In blood, the activity of dehydrogenases of the tricarboxylic acid cycle and creatine kinase decreased at the expense of its muscle isoenzyme and the activity of acid phosphatase, total alkaline phosphatase and bone isoenzyme of alkaline phosphatase increased.

Electrocardiographic parameters and serum concentrations of potassium, sodium, calcium (total and ionized) and magnesium in 6 essentially healthy men, aged 30-45 years, were measured before, during and after 120-day head-down tilt at -4.5 degrees. A close correlation was demonstrated between T-wave depression and serum concentrations of potassium (direct correlation) and calcium and magnesium (inverse correlation). No consistent changes in the sodium content during the 120-day test were seen. In spite of electrolyte changes in blood induced by head-down tilt, ECG variations showed minor hypokalemia that was not followed by any clinical symptoms. These data can be used to evaluate the status of healthy people exposed to prolonged hypokinesia and to develop adequate prophylactic measures.

Nine healthy male volunteers were exposed to head-down tilt (-4.5 degrees) for 120 days. The concentrations of parathormone, calcitonin, gastrin, growth hormone, total and ionized calcium were measured in plasma. Prolonged exposure to antiorthostatic hypokinesia led to significant changes in the hormonal regulation of calcium-phosphorus metabolism, the most important of which was an enhanced secretion of the parathyroid hormone. The increased concentration of calcitonin and gastrin was a secondary response to the higher content of ionized calcium. The phase-like changes in the somatotrophic hormone secretion were induced by variations in the parathormone concentration in blood, on the one hand, and by a reduction of plastic processes, on the other.

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.

The effect of 120-day bed rest on skeletal bones of 15 volunteers was investigated by noninvasive methods, viz. gamma-photon absorption, ultrasonic and neutron-activation analysis. The test subjects were divided into 4 groups one of which served as control and three others used different countermeasures (drugs, exercise or drugs in combination with exercise). Calcium loss in skeletal bones was not more than 0.5% per month; calcium loss in leg tubular bones was 1 to 2% per month in 6 test subjects; calcium loss in heel bones was on the average 3-4% per month in the control, exercise and combination groups. No strict correlation between the negative balance of calcium and mineral content in leg compact bones and foot spongy bones was found. There was a correlation between changes in the mineral content of leg bones and ultrasound propagation along certain compartments of the tibial median surface. In terms of negative and positive trends leg and foot bones were in better condition in the drug group. The techniques used were assessed with respect to their diagnostic and prognostic value.

Ten cosmonauts who performed 30- to 175-day space flights on board Salyut-4 and Salyut-6, and 50 test subjects exposed to head-down tilt (-4 degrees) for 182 days were examined. In actual and stimulated weightlessness renal excretion of calcium and potassium increased, reaching maximum during the 4-6th weeks. Before and after flight the test subjects were exposed to loading salt tests. Renal excretion of calcium and potassium in response to the loading tests with their salts postflight was much higher than preflight. During the potassium chloride load the aldosterone content in blood correlated with potassium excretion, and during the calcium lactate load an increase in calcium excretion was paralleled by a decrease in the parathormone content in blood. It is most likely that the negative balance of ions in weightlessness is associated with the reduced capacity of tissues to retain electrolytes due to the decreased ion pool. It was shown that electrolyte balance can be beneficially influenced by exercises.

This paper presents information about the goals, tasks and protocols of a 370-day antiorthostatic hypokinesia study. It describes the use of various methods of research and different countermeasures.

The paper presents the results of studying fluid-electrolyte metabolism and the renal function in A. A. Gubarev and G. M. Grechko after their 30-cay orbital flight. On the R + O day renal excretion of fluid, sodium, potassium and osmotically active subtances decreased. Renal excretion of calcium and magnesium postflight was higher than preflight. Similar, although better pronounced, changes were seen during provocative tests with a water load. One of the factors causing changes in the renal transport of electrolytes postflight could have been an alteration in the ionic composition of the serum, especially a decrease in the potassium concentration and an increase in the calcium and magnesium content. Disorders in the relationship between the function of osmo- and ion regulation systems and dissociation in the renal excretion of individual ions after the 30-day flight that were distinct during tests with a water load seem to be associated with metabolic changes during and after flight rather than with hemodynamic changes.