Adaptation of the water-electrolyte metabolism to space flight and at its imitation

A fifty-year study of water-electrolyte metabolism, the condition of the water medium of the body, and hormonal regulation during space flights and the postflight period or their on-ground modeling (hypokinesia, bed rest, immersion, etc.) has shown the important role of water-salt homeostasis in adaptation of the human and animal body to weightlessness. It has been revealed that, in weightlessness, the conditions for the development of a negative balance of a liquid (hydrohydration) and basic electrolytes are created. After termination of long space flights, attributes of the development of adaptive reactions, compensating for the loss of extracellular liquid volume come to light. In order to assess the state of the kidneys and water-electrolyte metabolism in cosmonauts and investigators, functional load tests, and special methods of diagnostics were developed. This is the basis for the research aimed at improving the scheme of correction of the water balance of the body of cosmonauts at different stages of a flight.     

Changes of insulin in plasma and receptor for insulin in various tissues after the exposure of rats to space flights and hypokinesia

The explanation of the mechanism of the response to gravity changes is of great importance for the determination of the capacity of human subjects to adapt to the load of gravitational stress. Therefore several studies were performed to investigate the activity of endocrine system, since the hormones are involved in the regulation of physiological functions and metabolic processes. However the studies of endocrine system activity during altered gravity conditions, especially during the weightlessness are influenced by the several interventions in biomedical observations due to operational program of astronauts, wide variability in individual response and tolerance, use of extensive countermeasures, differences in the type of space missions and in the studies after landing also a hypergravity effect at landing and variability in postflight readaptation process. The significant changes of plasma insulin and glucose levels were observed in astronauts during space flights and in the first days of recovery period. In the first inflight period plasma insulin levels were increased, unchanged or decreased however after 4-5 weeks of exposure to weightlessness a decrease of insulin plasma levels were noted. After space flights an increase of plasma insulin levels were demonstrated in experimental animals and in human subjects. Since plasma insulin level is considered as most important factor involved in the regulation for insulin receptors in target tissues, an investigation of insulin receptors in various tissues was performed in rats exposed to space flight or to hypokinesia (model used for simulation of some effects of microgravity).     

Functional load tests in the assessment of the state of the kidneys and water-electrolyte metabolism

The use of functional load tests to assess the specific features of water-electrolyte metabolism under extreme conditions is considered, with special emphasis on their implications for space physiology and medicine. Water and mineral metabolism, the kidney function, and their hormonal regulation during simulation experiments, as well as in spaceflights and in the readaptation period, play an important role in human adaptation to new conditions of vital activity. In order to assess the state of the kidneys and water-electrolyte metabolism in cosmonauts and investigators, functional load tests were developed. They enabled us not only to gain insight into the mechanisms of osmotic and volumetric regulation but also to develop countermeasures to correct unfavorable shifts in water-salt homeostasis.     

The influence of space flights on water-electrolytes turnover and its regulation

A study of water-electrolyte exchange, the condition of water milieu of the organism, and the volume- and electrolyte homeostasis regulation in space flights, and also in postflight period has shown the important role of the water-salt homeostasis in adaptation of the human and animal organism to weightlessness. Obviously, downturn of food consumption, renal excretion and the intestine output seem to be caused by suppression of activity of mechanisms of ion deposition. The most intensive changes of the liquid milieu volumes occur in the first days of weightlessness or in its ground simulation. And, with prolonged duration, the changes of extracellular liquid volume and the volume of plasma do not extend. After termination of long space flights, activation of renin-aldosterone systems occurs as well as a decrease in efficiency of antidiuretic hormone, misbalance of pressor/unpressor prostanoids. In the period of re-adaptation after space flights, development of desensitization of kidneys to endogenous ADH occurs. This is the basis for researches directed to improvement of the existing scheme of correction of the hydrogenous status of the astronaut organism in the closing stage of flight.     

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?     

Behavioral and functional vestibular disorders after space flight: I. Mammals

The review presents data on functional disorders in mammals caused by changes in the vestibular system after space flight. These data show that the mammalian vestibular system responds to weightlessness dissimilarly at different ontogenetic stages. During the embryonic period, orbital space flight conditions have a little effect on the developing vestibular system and even promote normal fetal development. During the early postnatal period, when optimal sensorymotor tactics arise, long-term exposure to space flight conditions leads to the development of novel, “extraterrestrial”, sensory-motor programs that may fixate in CNS for life. In adult individuals, substantial vestibular changes and disorders may occur immediately after landing depending on the weightlessness duration. An adult organism has to solve two concurrent and mutually conflicting problems: to adapt to weightlessness and not to adapt to it in order to facilitate readaptation after return. Thus, individuals have to counteract weightlessness to retain a maximum of their pre-flight health status. The means of such a counteraction have to be adjusted according to the weightlessness duration. It is noteworthy, however, that not all functional changes occurring in adult individuals under weightlessness can be adequately accounted for. Some of them can assume a chronic or even pathological character. The review raises for the first time the question of necessity to include into the scope of studies the effect of weightlessness on a senile (senescent) organism and its vestibular system. We believe that development of space gerontology as a special branch of space biology and medicine is undoubtedly of interest and may become practically important in the future in view of the ever-growing age of space explorers.     

Lipid peroxidation rate and the antioxidant protection system during the readaptation period after long-term space flights on board the International Space Station

The content of lipid peroxidation (LPO) products (diene conjugates (DC), malondialdehyde (MDA), Schiff bases (SB), and tocopherol (TP, a main lipid antioxidant) were measured in blood serum of 17 astronauts taking part in long-term (125–217 days) missions on board the International Space Station (ISS) during the preflight period, on the day of the landing, and on the 7th and 14th days after landing (the rehabilitation period, RP). A decrease in the DC and MDA levels against a background of an increase in TP has been found in a group of eight astronauts after landing on board the Space Shuttle spacecraft and a group of eight astronauts after a space flight on board the Soyuz TM in the course of RP. The changes in measured indices were more pronounced in the group of astronauts after the space flight on board the Space Shuttle spacecraft. Inhibition of LPO during RP was regarded as an adequate response to readaptation stress to the conditions on earth. The possible mechanisms of differences in the efficiency of LPO inhibition between groups are discussed: the changes in the biomembrane phase state under the conditions of deceleration load during disorbiting and the stressful reaction to landing on board different spacecrafts.     

地面模拟失重实验方法概况

虽然载人航天事业已得到突破性的进展,但航天员对失重的适应和返回地球后的再适应,无论在理论上还是实践中都是尚未攻克的技术难题。航天失重环境下航天飞行综合征的发生机理及对抗措施,仍是航天医学的重要课题。在地面上无法创造长期的失重环境,但根据失重对机体产生的生理效应可实现地面模拟失重实验。本文概述了地面模拟失重的人体实验、动物实验概况,为更好开展地面模拟失重条件下相关研究提供参考。     

Effect of weightlessness and artificial gravitation on thyroid gland morphology]

The investigation of the thyroid gland was carried out in Wistar rats, SPF colony 4.5--13 h and 25 days after a 18.5 days flight on board the space biosatellite "Cosmos-936". In animals subjected to weightlessness, moderate symptoms of the thyroid hypofunction were observed, statistically significant decrease in number and volume of the nuclei in calcitonin-secreting cells (C-cells) was especially pronounced during 4.5--9 h after landing. Similar but less pronounced changes were observed in C-cells of the rats subjected to artificial conditions of space flight, besides weightlessness. The similarity of the changes in the animals of both groups made it possible to connect the increasing amount of C-cells and the morphological symptoms of their functional inhibition with the effect of weightlessness and hypokinesia. During the space flight, the animals were kept under the conditions of artificial gravitation on board the biosatellite and therefore morphological peculiarities specific for the earth conditions were preserved in C-cells and the thyroid gland. Thus, it was concluded that artificial gravitation prevented the development of the thyroid changes which appeared under the influence of weightlessness.     

Stress under normal conditions, hypokinesia simulating weightlessness, and during flights in space

Stress due to intensive mental work under normal conditions was compared to stress under a sharp limitation of motor activity (hypokinesia), simulating weightlessness on the human body. Mental stress causes typical alterations of cerebral circulation under normal conditions: increase of blood flow in the supramarginal and angular gyri of the parietal lobe, in the frontal lobe, and in the superior temporal gyrus of the left hemisphere, and changes in cardiac activity and in the tonus of vessels. Dynamics of human stress reactions, among other features of this process, is best reflected in the parameters of a electrocardiogram, a rheoencephalogram, and total peripheric vascular resistance. An increase in the latter is an informative index of stress development. Human reaction to stress under hypokinesia and during flights in space have specific features. Prolonged hypokinesia causes an imbalance in an organism's control systems, specifically depressor reactions are distorted. In the context of hypokinesia, anxiety and mental stress lose their adaptive nature to a large extent. They provoke disturbances of the heartbeat and hypertensive reactions. A whole complex of factors affects the living organism during space flights. An imbalance of the body's control systems, emotional and physical overloads, which arise episodically, changes in electrolyte and energetic metabolism, and alterations in the head vessels increase the probability of reactions to stress and reinforce their effect. Stress can be retarded by using on elaborated system of preventive measures which includes physical training, psychological support of astronauts and, to some degree, reduction of the hypothalamus adrenergic centers' tonus through muscle relaxation. Astronauts' reactions to being in space occur during flights under heavy loading tests and in emergency situations. Weightlessness does not generate stress when one has adapted to it. Returning from weightlessness to the Earth's gravitation causes stress. After prolonged flights, stress associated with readaptation to the Earth's gravitation is atypical in character (increase of sympatoadrenalic system activity against the background of a reduction in hypothalamo-hypophysial system activity). We explain the voltage decrease of the T-wave of the electrocardiogram, the phenomenon repeatedly occurring both during prolonged space flights and under hypokinesia, by a lowering of cardiomyocytes, energetic potential due to hypokalemia, insufficient glucose usage, and a decrease in the coupling of oxidative phosphorylation processes. [Translated from Fiziologiya Cheloveka, vol. 22, no. 2, 1996, p. 10-19]     

Circulatory and hormonal changes induced by microgravity

The absence (or decrease) of the hydrostatic pressure during space flights (microgravity state) or simulations of weightlessness (by immersion, bed rest or head-down tilt) result in a body fluid shift and an engorgement of the central circulation where mechanoreceptors involved in plasma volume regulation are located. Their activation induces the initial (first hours) hormonal response with a decrease in plasma vasopressin, renin and aldosterone and probably an increase in a natriuretic factor (Gauer reflex). Prolonged exposure to microgravity leads to more complex and often hypothetical responses: cardiovascular deconditioning, modifications in secretion and circadian rhythms of above cited hormones. After 24 years of studies on approximately 200 astronauts our knowledge of cardiovascular and hormonal adaptation to space flight is still at the beginning.     

Recording of blood pressure,heart rate and aortic nerve activity during parabolic flight in the rat via radio-telemetry

Exposure to microgravity induces cardiovascular deconditioning characterized by orthostatic hypotension when astronauts return to the earth. In order to understand the mechanism of cardiovascular deconditioning, it is necessary to clarify the changes in hemodynamics and the cardiovascular regulation system over the period of space flight. The telemetry system applied to freely moving animals will be a useful and appropriate technique for this kind of long term study of the cardiovascular system in the conscious animal during space flight. The purpose of the present study is twofold: firstly, to observe the detailed changes of arterial pressure and heart rate (HR) during microgravity elicited by the parabolic flight in order to study the acute effect of microgravity exposure on the cardiovascular system; and secondly, to test the feasibility of the telemetry system for recording blood pressure, HR and autonomic nervous activities continuously during space flight.     

Physiological analysis of the possible causes of hypoxemia under conditions of weightlessness

It was found that the partial oxygen tension in the capillary blood in astronauts during a space flight was 12–30% lower than that before the space flight. Analysis of the possible causes and mechanisms of hypoxemia was performed, which made it possible to conclude that an increase in the venous blood flow that passes through the lungs and does not undergo complete gas exchange in the pulmonary capillaries is most likely to be the main cause of the decrease in the oxygen tension in the blood in astronauts under conditions of weightlessness.     

Bone formation induced by a novel form of mechanical loading on joint tissue.

Because of insufficient mechanical loading, exposure to weightlessness in space flight reduces bone mass. In order to maintain bone mass in a weightless condition, we investigated a novel form of mechanical loading--joint loading. Since some part of gravity-induced loading to our skeletal system is absorbed by viscoelastic deformation of joint tissues, we hypothesized that deformation of joint tissues would generate fluid flow in bone and stimulate bone formation in diaphyseal cortical bone. In order to test the hypothesis, we applied directly oscillatory loading to an elbow joint of mice and conducted bone histomorphometry on the diaphysis of ulnae. Using murine femurs ex vivo, streaming potentials were measured to evaluate a fluid flow induced by joint loading. Bone histomorphometry revealed that compared to no loading control, elbow loading increased mineralizing surface, mineral apposition rate, and bone formation rate 3.2-fold, 3.0-fold, and 7.9-fold, respectively. We demonstrated that joint loading generated a streaming potential in a medullar cavity of femurs. The results support a novel mechanism, in which joint loading stimulates effectively bone formation possibly by generating fluid flow, and suggest that a supportive attachment to joints, driven passively or actively, would be useful to maintain bone mass of astronauts during an exposure to weightlessness.     

Effect of microgravity on plasma catecholamine responses to stressors during space flight

The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.     

Mechanism for negative water balance during weightlessness: an hypothesis

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.     

Urinary albumin in space missions

Proteinuria was hypothesized for space mission but research data are missing. Urinary albumin, as index of proteinuria, was analyzed in frozen urine samples collected by astronauts during space missions onboard MIR station and on ground (control). Urinary albumin was measured by a double antibody radioimmunoassay. On average, 24h urinary albumin was 27.4% lower in space than on ground; the difference was statistically significant. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).     

Endocrine, renal, and circulatory influences on fluid and electrolyte homeostasis during weightlessness: a joint Russian-U.S. project

Microgravity is known to have a substantial effect on fluid homeostasis. The research described here was planned as part of the first joint Russian-U.S. science program carried out during a Shuttle flight. The aim of the program was to study the nature of the changes in fluid homeostasis induced by microgravity, as well as to determine the possible mechanisms underlying the regulation of fluid balance under conditions of spaceflight. To determine the effects of spaceflight on the homeostasis of fluid and electrolytes, measurements were taken of total body water, extracellular fluid plasma volumes, levels of regulatory hormones, and nutrient consumption before, during, and after a nine-day flight. Changes in renal function were studied before and after the flight. In these 2 subjects, weightlessness was not associated with a decreased extracellular fluid volume. However, there were the characteristic decreases in plasma atrial natriuretic peptide concentrations, and increases in plasma and urinary cortisol. Results indicated decreased urine volume, even through the first 48 hours of flight. Fluid volumes and glomerular filtration rate were increased after landing, probably related to the saline-loading countermeasure used by Shuttle crewmembers. The information obtained as a result of this research will facilitate the development of future research programs, as well as preventive measures for future long-duration spaceflights.     

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.     

The effect of space flight conditions on the rate of multiplication, morphology of cells, DNA and protein content in the ciliate Tetrahymena pyriformis

The conditions of a space flight and, in particular, the weightlessness promote an increased density of the ciliate culture, an enhanced reproduction rate, and an elevated ratio of dividing cells. The condition of weightlessness brings about some decrease in the bulk protein content of the cells determined by cytophotometry of Naphthol-yellow stained ciliates. The quantity of DNA in macronuclei was measured following the routine Feulgen procedure (its "cold" variant). The DNA content was found to remain unchanged. Some changes in the shape and size of the cells were noticed under flight conditions: ciliates that had developed in weightlessness appeared more spherical than control ones, due presumably to a decrease in the body length and to some extension in the body width. The conditions of space flight, including the weightlessness, induce changes in the physiological status of unicellular organisms. A decrease in the gravitation force may lead to a decrease in the energy expenditures for maintenance of the cell positional homeostasis.