The water-salt balance and renal function in space flights and in model experiments

Study of a condition of mineral and water-electrolyte metabolism, function of kidneys, and their hormonal regulation during model experiments (hypokinesia, bed rest, immersion etc.), and also in space flights and in readaptation period, has shown a major role of water-electrolyte homeostasis during general adaptation of humans and animals to new conditions of life and to conditions of weightlessness in particular. The change in regulation of volumes of fluid milieu in an initial period of weightlessness was shown to be the consequence of redistribution of blood and hemodynamics of the shifts resulting in change of production of volume-regulation hormones, formation of negative water balance, and redistribution of fluid in the organism among various fluid compartments. At later stages of flight or long-term hypokinesia, a change of water-electrolyte homeostasis occurs with a decrease in the kidneys excretion of sodium, and diuresis, but with an increased excretion of calcium and production of ADH and RAAS hormones. Following returning to earth gravitation, the majority of astronauts have adaptive reactions, compensating for the loss extracellular fluid and mineral substances and formation of "earth" water-electrolyte homeostasis. For estimation of water-electrolyte homeostasis and the functions of kidneys in astronauts, various functional loading tests have been developed. The developed system of preventive maintenance is successfully used for abolition of adverse changes at various stages of space flight and in readaptation period.     

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.     

The volume of extracellular fluid under conditions of long-term space flights

The volume of extracellular fluid (the bromine space) was determined in 18 cosmonauts 30 days before the start of a space flight and on the first day after landing. The duration of space flights on the Mir orbital station was from 126 to 438 days. Moreover, the volume of extracellular fluid was determined in seven cosmonauts directly during long-term space flights approximately two weeks before landing. After long-term space flights, the volume of extracellular fluid was decreased in all cosmonauts studied. The bromine space volume was significantly decreased compared to its initial preflight value. A decrease in the volume of extracellular fluid was caused not only by the reduction in the dense mass of the body but also by its dehydration. These processes developed independently of the duration of weightlessness but are mainly determined by the individual features of human beings.     

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).     

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.     

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]     

Plasma hormone levels in human subject during stress loads in microgravity and at readaptation to Earth's gravity

In great part of the investigations of endocrine system functions in astronauts during space flights the plasma levels of hormones and metabolites were determined only in resting conditions, usually from one blood sample collection. Such levels reflected the psychical and physical state and new hormonal homeostasis of organism at the time of blood collection, however, the functional capacity of neuroendocrine system to respond to various stress stimuli during space flight remained unknown. The aim of present investigations was to study dynamic changes of hormone levels during the stress and metabolic loads (insulin induced hypoglycemia, physical exercise and oral glucose tolerance test) at the exposure of human subject to microgravity on the space station MIR. The responses of sympatico-adrenomedullary system to these stress and workloads were presented by Kvetnansky et al.     

Endocrine responses to space flights

Simultaneously with human space flights several series of observations were performed by using experimental animals--mainly rats--exposed to space flights on board of special satellites BION-COSMOS or in Shuttle Transportation Systems (STS). The aims of these experiments were to study in more details: the mechanisms of the changes in bones and skeletal muscle, the alterations of the function of immune system, the radiation effects on organism, the mechanism of the changes of endocrine functions, the evaluation of the role of hormones in alteration of metabolic processes in organism. The advantages of these animal experiments were the possibilities to analyze not only the plasma samples, but it was possible to obtain samples of organs or tissues: for morphological and biochemical analysis for studies of the changes in enzyme activities and in gene expressions, for measurement of metabolic processes and for investigation of the hormone production in endocrine glands and estimation of the response of tissues to hormones. It was also possible to compare the endocrine response to spaceflight and to other stress stimuli. These animal studies are interesting for verification of some hypothesis in the mechanism of adaptation of human organism to the changes of gravity. The disadvantage was, however, that the animals in almost all experiments could be examined only after space flight. The actual inflight changes were investigated only in two SLS flights. In this short review it is not possible to evaluate all hormonal data available on the response of endocrine system to the conditions of space flights. Therefore we will concentrate on the response of pituitary adrenocortical system, pituitary thyroid and pituitary gonadal functions.     

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.     

Microgravity and the lung.

Although environmental physiologists are readily able to alter many aspects of the environment, it is not possible to remove the effects of gravity on Earth. During the past decade, a series of space flights were conducted in which comprehensive studies of the lung in microgravity (weightlessness) were performed. Stroke volume increases on initial exposure to microgravity and then decreases as circulating blood volume is reduced. Diffusing capacity increases markedly, due to increases in both pulmonary capillary blood volume and membrane diffusing capacity, likely due to more uniform pulmonary perfusion. Both ventilation and perfusion become more uniform throughout the lung, although much residual inhomogeneity remains. Despite the improvement in the distribution of both ventilation and perfusion, the range of the ventilation-to-perfusion ratio seen during a normal breath remains unaltered, possibly because of a spatial mismatch between ventilation and perfusion on a small scale. There are unexpected changes in the mixing of gas in the periphery of the lung, and evidence suggests that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a few acini. In addition, aerosol deposition in the alveolar region is unexpectedly high compared with existing models.     

The bio-rhythmic problems of a space flight

The influence of space-flight factors on the organism's circadian periodicity is discussed. It is shown that in mechanisms of such influence, the transformation of natural structure of Zeitgebers accompanying a space flight, can play the essential role. It is confirmed by the results of ground research carried out in conditions of isolation simulating the usual space flight transformation of Zeitgebers system. The data obtained in the ground researches with isolation, testify that the changes of circadian rhythms in these conditions are similar to those in space flights and frequently are interpreted as the result of influence of weightlessness. Special attention is paid to phenomenon of delay of the daily maximum and to possible connection of this phenomenon with the tendency to transition of rhythmic process in a free-running regime.     

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.     

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?     

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.     

Reflex response changes during hyper and microgravity

This paper reports the quantitative evaluation of the H-reflex exhibited by parabolic flight with exposure to micro and high-gravity. With respect to previous findings in parabolic flights and short-term space missions, the analysis focused on reflex activity in weightlessness. The aim of this study was to investigate the effect of gravity on H-reflex and motor evoked potentials (MEP) in soleus muscle (SOL) during parabolic flight.     

Structural and metabolic characteristics of human soleus fibers after long duration spaceflight

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.     

REGULATION OF HAEMOPOIESIS IN ALTERED GRAVITY

(1) The aetiology of one of the most striking physiological changes occurring during space-flight, the loss of red blood cells, remains unknown, and its precise time-pattern in flight has not yet been studied. (2) It is suggested that the changes during space-flight responsible for loss of red blood cells in man are (a) loss of plasma volume resulting from disappearance of hydrostatic pressure in the circulation during weightlessness and (b) reduced energy expended in maintenance of form, posture and locomotion resulting from elimination of the usual gravitational load on the muscles. Quadrupeds, like rats, would be expected to suffer minimal blood shifts in weightlessness and therefore have an unchanged plasma volume. However, since in weightlessness the activity-related energy expenditure by the muscles is reduced, the accompanying reduced oxygen demand by the tissues would cause a reduction in erythropoietin levels and so in the production of red blood cells, and a progressive lowering of the total red blood cell mass toward a new steady-state level. (3) Loss of plasma volume alone does not explain the observed loss of red blood cells in astronauts because, in the three manned Skylab missions, as the duration of the missions increased, loss of red blood cell mass decreased, whereas loss of plasma volume increased. This discrepancy is, however, well accounted for by the above hypothesis by taking into consideration the increased level of exercise of the astronauts as the duration of the mission increased. (4) Though water submersion of human subjects does mimic the effects of weightlessness, such effects were overriden in sea mammals because of adaptation to other factors associated with a life in the sea. (5) From the presented analysis of haemopoietic changes observed in spaceflight, an experiment can be designed for a future flight to uncover the causes and mechanisms of these changes and provide a basis for developing protective measures. Thus, the space environment can be used as an investigative tool to enhance the knowledge of the function of the haemopoietic system, which is a major homeostatic system of man and other vertebrates.     

Pulmonary diffusing capacity and pulmonary capillary blood volume during parabolic flights

Vaïda, Pierre, Christian Kays, Daniel Rivière,Pierre Téchoueyres, and Jean-Luc Lachaud.Pulmonary diffusing capacity and pulmonary capillary blood volumeduring parabolic flights. J. Appl.Physiol. 82(4): 1091-1097, 1997.Data from theSpacelab Life Sciences-1 (SLS-1) mission have shown sustained butmoderate increase in pulmonary diffusing capacity(DL). Because of the occupational constraints of the mission, data were only obtained after24 h of exposure to microgravity. Parabolic flights are often used tostudy some effects of microgravity, and we measured changes inDL occurring at the very onsetof weightlessness. Measurements ofDL, membrane diffusing capacity,and pulmonary capillary blood volume were made in 10 male subjectsduring the 20-s 0-G phases of parabolic flights performed by the"zero-G" Caravelle aircraft. Using the standardized single-breathtechnique, we measuredDL for CO andnitric oxide simultaneously. We found significant increases inDL for CO (62%),in membrane diffusing capacity for CO (47%), inDL for nitric oxide (47%), andin pulmonary capillary blood volume (71%). We conclude that majorchanges in the alveolar membrane gas transfers and in the pulmonarycapillary bed occur at the very onset of microgravity. Because thesechanges are much greater than those reported during sustainedmicrogravity, the effects of rapid transition from hypergravity tomicrogravity during parabolic flights remain questionable.

     

Bone mineral and lean tissue loss after long duration space flight

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.     

Oxidative phosphorylation in rat skeletal muscles after space flight on board biosatellites

Polarographic analysis of biological oxidation in rat's skeletal muscles after the 18- and 22-day flights revealed changes specific for the flight animals: oxidative phosphorylation uncoupling, distinct inertness of energy accumulation after 10 hrs of landing. Tissue respiration's inhibition was observed in both flight and synchronous rats suggesting the effect of other than microgravity factors. Energy metabolism in muscles of flight animals returned to the pre-flight level later (29 d) compared to the synchronous rats (6 d). Muscles of different functions (predominance of fast or slow fibers) showed similar responses of energy metabolism to weightlessness, i.e. inhibition of the intensity and decline of the energy efficiency of oxidative processes. A decrease in dehydrogenase activity has been found in the first day of recovery. The effects may be caused by the inhibition of both aerobic and anaerobic metabolism after space flight.