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Antinatriuretic kidney response to weightlessness.

We have tested the effects of weightlessness on renal function in one subject who flew the recent week-long Russian-German MIR'92 space mission. Urine flow, renal sodium excretion, and the excretion of urodilatin were measured during the first and last days of the flight. Our results demonstrated, in contrast to expectations, that urine flow and sodium excretion during weightlessness were actually lower than the values obtained during preflight measurements. These results therefore are inconsistent with the commonly held hypothesis that weightlessness induces a diuresis and natriuresis in human subjects. It would seem that further studies are necessary to resolve this issue and to determine whether currently used ground-based models of weightlessness correctly predict physiological adaptations that occur during space flight.

Atrial Natriuretic Factor↗

Postural reactions of circulation and its regulation during simulated weightlessness.

The extention and intensification of space exploration the influence of weightlessness on human organism and the formation of a new level of adaptation. The studies of blood circulation is very important because of frequent occurrence of cardiovascular disorders in the middle age subjects. In connection with extension and intensification of space exploration the influence of weightlessness on human organism and the formation of a new level of adaptation mechanisms acquires a special significance. The data obtained in recently undertaken model experiments and also during space flights indicate that weightlessness in many ways affects various physiological systems of organism, and first of all cardiovascular system with the development of reflex, humeral and metabolic reactions. It also indicates, that the changes in functioning of cardiovascular system brings about the disruption of its regular responses, which is foremost expressed in decreased antigravitational response, which manifests itself in lowered orthostatic stability. It is worth mentioning, that the changes during previous investigations of haemodynamics were mainly carried out with the subjects under forty, therefore age related specific features of blood circulation system response are described in a few articles. The studies of the kind are especially important because of frequent occurrence of cardiovascular disorders such as heart and brain vessels atherosclerosis, hypertension in the middle age, which can to a great extent complicate and affect the "acute" period of adaptation to weightlessness and readaptation process.

Adaptation, Physiological↗

Gravity, weightlessness and the genetic structures of organisms.

The whole evolution of life on earth has proceeded under the action of earth's gravity which must have influenced the structure and function of organisms. During space flights organisms are exposed to the entirely new condition of weightlessness, and to variations in gravity that produce various changes. Current flight data suggest that organisms most often respond to weightlessness by disturbances in physiological function, which are reversible after the brief exposures that have at present been possible. Only longer space flights will show whether these changes will be compensated, or will lead to alterations in the more important systems of organisms including their hereditary properties. There is evidence that weightlessness has a direct effect on genetic properties. Thus, in microspores of Tradescantia abnormal mitoses (that were not observed in the ground-based control) were recorded to an extent of 3%. The numerous changes in various vital systems suggest that for terrestrial organisms weightlessness is a factor which, if administered for a long time, may bring about serious disturbances in their activities and heredity. The higher the evolutionary position of the organism, the more pronounced the effect is likely to be.

Adaptation, Physiological↗

Weightlessness acts on human breast cancer cell line MCF-7.

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1 g in-flight and ground controls. Post-flight, fluorescent labeling was performed to visualize cell proliferation (Ki-67), three cytoskeleton components and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Several main phenomena were observed in weightlessness: The perinuclear cytokeratin network and chromatin structure were looser; More cells were cycling and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade; Microtubules were altered in many cells. The results reported in the first point are in agreement with basic predictions of cellular tensegrity. The prolongation of mitosis can be explained by an alteration of microtubules. We discuss here the different mechanisms involved in weightlessness alteration of microtubules: i) alteration of their self-organization by reaction-diffusion processes, and a mathematical model is proposed, ii) activation or deactivation of microtubules stabilizing proteins, acting on both microtubule and microfilament networks in cell cortex.

Actin Cytoskeleton↗

Haematocrit, plasma volume and noradrenaline in humans during simulated weightlessness for 42 days.

Previous results from our laboratory demonstrate that changes in haematocrit (Hct) and haemoglobin concentration (Hb) underestimate the relative (%) change in plasma volume (PV) in seated subjects during simulation of weightlessness by water immersion. Therefore, we examined whether changes in Hct and Hb would accurately reflect the changes in PV in seven subjects during simulation of weightlessness by another model, 6 degrees head-down tilted bed rest (HDBR), for 42 days. Since we have previously observed unexpectedly high plasma levels of noradrenaline (NA) in astronauts during space flight, we also took the opportunity to measure this variable. The measurements were compared with those of the supine horizontal position before and after HDBR. During HDBR, PV measured by the Evans blue dye dilution technique decreased by 6.1 +/- 2.8% (P < 0.05) on day 2 and 9.6 +/- 2.2% (P < 0.05) on the 42nd day compared with that of the supine, horizontal position. Based on changes in Hct and Hb, PV decreased similarly by 8.3 +/- 2.8 and 10.2 +/- 3.2% (P < 0.05) respectively. There were no differences comparing the results of the two methods (P > 0.05). Forearm venous plasma NA was unchanged during the whole course of HDBR compared with that of the pre-HDBR supine position. It is concluded that changes in Hct and Hb reliably reflect the changes in PV comparing prolonged HDBR with the pre- and post-HDBR horizontal, supine position. Thus, changes in Hct and Hb might accurately reflect the change in PV during weightlessness in humans provided that the horizontal supine position is used as the ground-based reference. Furthermore, the results of this study, as well as of previous studies from space, confirm that NA release is unchanged or even increased during weightlessness.

Adult↗

[Effects of simulated weightlessness on the hypophyseal-cortical-adrenal axis in the pregnant rat].

The eventual part of stress in the hormonal responses to simulated weightlessness was studied during gestation in the rat. We have compared these responses with the effects of two other situations well-known to provoke stress: ultrasounds and denutrition. An increase of blood and adrenal corticosterone levels was found in mothers after denutrition, neither after ultrasounds nor after simulated weightlessness. In foetuses, a decrease of weight was noted after denutrition and simulated weightlessness. Foetal suprarenal corticosterone remained normal when mothers were submitted to simulated weightlessness. In this group, a decrease in foetal weight was found that could be explained by non suprarenal hormonal factors or by circulation disturbances.

Animals↗

Effect of a simulated weightlessness model on the production of rat interferon.

A rat model simulating some aspects of weightlessness was used to determine whether simulated weightlessness might alter interferon production. The optimum time for in-vivo induction of alpha/beta interferon (alpha/beta-IFN) by polyriboinosinic-polyribocytidylic acid was determined to be four hours in normal, mature rats. Rats suspended in the model for two weeks were injected with polyriboinosinic-polyribocytidylic acid and bled four hours later. A dramatic decrease (80%) in alpha/beta-IFN production was observed in those animals exposed to simulated weightlessness as compared to control rats. These data suggest that weightlessness may alter certain immunological functions.

Animals↗

Simulated weightlessness alters the nycthemeral distribution of energy expenditure in rats.

The energy metabolism adaptations to simulated weightlessness in rats by hindlimb tail suspension are unknown. 12 male rats were assigned to 7 days of isolation, 7 days of habituation to the suspension device, 10 days of simulated weightlessness, and 3 days of recovery. The 24-hour energy expenditure was measured by continuous indirect calorimetry. We calculated the 12-hour energy expenditure during the active (night) and inactive (day) periods, the minimal observed metabolic rates with the day values taken as an index of the basal metabolic rate, and the non-basal energy expenditure representing the cost of physical activity plus the diet-induced thermogenesis. Suspension did not change the mean 24-hour energy expenditure (360.8+/-15.3 J min(-1) kg(-0.67)), but reduced the night/day difference by 64 % (P<0.05) through a concomitant drop in night-energy expenditure and increase in day values. The difference between night and day minimal metabolic rates was reduced by 81 % (P<0.05), and the transient rise in day values suggests an early and moderate basal metabolic rate increase (9 %). An overall 19 % reduction in non-basal energy expenditure was observed during simulated weightlessness (P<0.05), which was mainly attributable to a reduction in the cost of physical activity. 3 days of recovery restored the night/day differences but increased the 24-hour energy expenditure by 10 % (P<0.05). In conclusion, hindlimb tail suspension in rats did not alter the 24-hour energy expenditure, but it transiently increased the basal metabolic rate, and altered both the energy expended on physical activity and the nycthemeral distribution of motor activity. These data suggest that the circadian rhythms of energy expenditure are affected during simulated weightlessness.

Animals↗

Physiologic mechanisms effecting circulatory and body fluid losses in weightlessness as shown by mathematical modeling.

The mechanisms causing large body water losses in weightlessness are not clear. It has long been considered that a central volume expansion drives the physiologic adaptation to a reduced total blood volume, with normal blood composition eventually regained. However, inflight venous pressure measures suggest that central volume expansion in weightlessness may be very transient, or that considerable cardiovascular adaptation to fluid shifts occurs on the ground while astronauts wait in the semi-supine pre-launch position. If a central volume stimulus does not persist, other mechanisms must drive the adaptation of circulation to a reduced blood volume and account for body fluid losses. Recent results from the SLS-1 mission suggest that body fluid volumes do not simply decline to new equilibria but that they decrease to a low point, then undergo some recovery. Similar "under-shoots" of body fluid volumes have also been shown in computer simulations, providing confidence in the validity of the model. The purpose of this study was to examine the mechanisms which could explain the loss of body fluids in weightlessness and how a cardiovascular preadaptation countermeasure we previously tested ameliorated body fluid losses. It is assumed that the physiology of head down tilt (HDT) provides a reasonably accurate analog of weightless exposure.

Blood Viscosity↗

Effects of simulated weightlessness on the release of PGE2 in rat calvarial osteoblasts induced by flow shear stress.

OBJECTIVE: To observe the effects of simulated weightlessness on the release of prostaglandin E2 in rat calvarial osteoblasts by flow shear stress (FSS). METHOD: Osteoblasts were isolated from neonatal rat calvariae and then were set to two groups. One was cultured in 1 G terrestrial gravitational environment. The other was cultured on a clinostat (simulating weightlessness environment) for 60 h, then the osteoblasts were treated with 0.5 Pa or 1.5 Pa FSS in a flow chamber for 1 h. Then release of PGE2 in the osteoblasts was determined. RESULT: 0.5 Pa and 1.5 Pa FSS treatments significantly increased the release of PGE2 in osteoblasts cultured in 1 G environment (P < 0.01) , but there was no remarkable difference between the responses of 0.5 Pa FSS treatment group and 1.5 Pa group (P > 0.05). By contrast, in cells cultured in simulated weightlessness environment, no detectable release of PGE2 was found with the treatment of 0.5 Pa FSS (P < 0.01). The release of PGE2 was delayed and the amount of PGE2 Production was remarkably decreased with 1.5 Pa FSS treatment (P < 0.01). CONCLUSION: These results demonstrated that the responsiveness of osteoblasts to FSS was down-regulated in simulated weightlessness.

Animals↗

[Effects of simulated weightlessness on T cell subpopulations and activity of IL-2 and IL-6 in mice].

OBJECTIVE: To observe the effects of simulated weightlessness on the immunogenic activities in mice. METHOD: T cell subpopulations and the activity of IL-2 and IL-6 were observed in mice after exposure to head-down (-30 degrees) tail suspension for 3 d and 7 d. RESULT: The activity of IL-2 and IL-6 in mice showed no change after simulated weightlessness for 3 d compared with the control group. But after simulated weightlessness for 7 d, CD3+ and CD4+ were markedly reduced (both P< 0.01) and CD8+ and CD4+/CD8+ also tended to decrease; the activity of IL-2 was significantly decreased, while the activity of IL-6 tended to increase. CONCLUSION: Simulated weightlessness for 7 d had significant effects on T cell subpopulations and the activity of certain cytokines in mice.

Animals↗

[Effects of simulated weightlessness on the expression of cyclooxygenase-2 in rat calvarial osteoblasts induced by fluid shear stress].

OBJECTIVE: To investigate the effect of simulated weightlessness on mechanotransduction in rat calvarial osteoblasts. METHOD: Osteoblasts were isolated from neonatal rat calvariae and then were set to two groups. One was cultured in clinostat to simulate the weightlessness environment. Another was cultured in 1 G gravitational environment. After 60 h, osteoblasts were treated with 0.5 Pa or 1.5 Pa FSS in a flow chamber. The FSS treatment time was set to 30 min and 60 min, respectively. The specimens of each group were obtained for immunohistochemistry staining and determination of expressions of cyclooxygenase-2 (COX-2) in osteoblasts. RESULT: In osteoblasts cultured in 1 G gravitational environment, COX-2 expression was increased remarkably from 30 min to 60 min with the treatment of FSS (P<0.01). There was no clear difference between the expression of COX-2 after treatments of 0.5 Pa or 1.5 Pa FSS; In cells cultured in simulated weightlessness environment, no detectable expression of COX-2 was found with the treatment of 0.5 Pa FSS. The expression of COX-2 was only detected after 60 min treatment of 1.5 Pa FSS, but the level of expression was decreased significantly (P<0.01). CONCLUSION: These results demonstrated that the mechanotransduction in osteoblasts was down-regulated in simulated (correction of stimulated) weightlessness.

Animals↗

Significance of vestibular organs in problems of weightlessness.

Two important questions concerning the organs of equilibrium are posed by orbital and space flights. The first is whether exposure to weightlessness may evoke symptoms of vestibular origin, and the second is how to prevent symptoms of vestibular origin should it be decided to abolish weightlessness by causing the spacecraft to spin. It is important to determine whether vestibular symptoms are to be ascribed to the otolith apparatus or to the semicircular canals, or to both. During exposure to weightlessness the usual gravitational stimulus to the otolith apparatus is lost, and this reduction in afferent input might be expected to disturb the integrative patterns in the central nervous system. All such disturbances are special instances of a common cause for the appearance of functional syndromes such as seasickness. If orbiting vehicles are caused to rotate in order to abolish weightlessness, the angular velocity will be determined by the effective radius of rotation and the rate of spin, i.e., how nearly it is desired to simulate 1 g. At very short radii the complicating effects of exposure of the body to variations in centripetal force must be considered. With longer radii the principal stress will arise as a result of constant rotation, which, in combination with head movements, generates Coriolis forces. These forces cause bizarre patterns of stimulation of the semicircular canals which in turn may result in illusions and "canal sickness". This type of motion sickness has its origin in the semicircular canals and deserves the term "canal sickness". The angular velocities which represent a negligible stress or a tolerable stress are defined. A brief description is given of illusory phenomena and other manifestations together with the time-course of the adaptive process.

Acceleration↗

[Contribution to the study of the effects of weightlessness on the central nervous system of the rat].

We have studied the effects of various states of acceleration on the physiological activity of white rats. Initial experimental trials were carried out in the course of a flight of the Veronique missile. In another series of experiments the trials took place in an airplane in the course of successive parabolic flights at several minutes intervals producing periods of weightlessness of 33 to 44 seconds. We recorded the electrical activity of a large area lying between one electrode located in the somesthesic area and another electrode located in the homolateral visual area. In addition, cardiac and respiratory rate and electrical activity of the mesencephalic reticular formation and of the muscles of the neck were recorded. We found an intense cortical activation during the entire duration of the missile flight. In the airplane during the periods of weightlessness basic electrical activity has not been modified. Recordings of electrical activity in the mesencephalic reticular formation do not show any modification during missile flight. Afterwards appeared a flattening with the reduction of frequency. In the course of periods of weightlessness in airplane flight we have observed no modification of background electrical activity. Recording of neck muscle potentials shows, during weightlessness in airplane flight, a distinct augmentation of background tone. These findings seem in favor of a facilitation of reticular origin as a result of the abrupt diminution of volume of sensory information following the disappearance of the stimulus of gravity.

Acceleration↗

[Echocardiographic assessment of left ventricular structure and function after simulated weightlessness in rats].

Objective. To investigate whether the changes in rat after simulated weightlessness are similar to those in astronaut after flight. Methods. The effects of 4 wk tail-suspension on left ventricular structure and function in rats were examined by echocardiography. Results. After 4 wk of simulated weightlessness, the thickness of both the anterior and posterior wall in left ventricle (LV) showed a general trend of decrease, but these changes were not statistically significant; the end-systolic and end-diastolic internal dimensions (ESD and EDD respectively) of LV decreased significantly; and the end-systolic volume, end-diastolic volume and stroke volume (ESV, EDV and SV respectively) were all reduced; so did the relevant indices of them. There were no significant differences in ejection fraction (EF) and fractional shortening (FS) between the tail-suspended and control groups. The left ventricular mass (LVM) and its index (LVMI) were decreased. The peak velocities of blood flow of aorta, pulmonary artery and mitral valve didn't show any significant change after simulated weightlessness. Conclusion. Medium-term simulated weightlessness may lead to a significant decrease in left ventricular internal dimension, ventricular volume, and mass, and a trend of decrease in mean left ventricular wall thickness. These changes in rats are similar to those observed in astronauts postflight.

Animals↗

[Effects of rotating clinostat simulated weightlessness on the differentiation-related gene expression of ROS17/2.8 cells].

OBJECTIVE: To investigate the effects of rotating clinostat simulated weightlessness on the differentiation-related gene expression of ROS17/2.8 (rat osteosarcoma) cells. METHOD: Cultured ROS17/2.8 cells were exposed to rotating clinostat simulated weightlessness for 24, 48 and 72 h with control group in 1 G condition. Total RNA in cells was isolated and reverse transcription PCR analysis was made. Gene expression of type I collagen alpha 1 chain and alkaline phosphatase were examined by their ratios to beta-actin. RESULT: The expression of type I collagen alpha I chain and alkaline phosphatase (ALP) gene was significantly lower after 72 h exposure to clinostat simulated weightlessness than that of the control group (P<0.01). CONCLUSION: Differentiation of rat osteosarcoma cells was reduced after exposure to rotating clinostat simulated weightlessness for 72 h.

Alkaline Phosphatase↗

[Changes in voltage-dependent calcium channel currents of vascular smooth muscle cells isolated from small mesenteric arteries of simulated weightless rats].

The aim of the present study was to examine the changes in the function of voltage-dependent calcium channels (VDC) of vascular smooth muscle cells (VSMCs) isolated from small mesenteric arteries of rats subjected to 1-week or 4-week simulated weightlessness. The whole-cell recording mode was used to record current densities and Ba(2+) was used as charge carrier. Curves and fitting parameters describing steady-state activation and inactivation characteristics of VDC were thus obtained. The inward currents recorded from the VSMCs of small mesenteric arteries were mainly the Ba(2+) currents through the long-lasting type VDC (L-VDC). Compared with that of the control rats, the L-VDC current density of VSMCs from small mesenteric arteries showed a trend toward a decrease in the rats after 1-week , while a significant decrease was observed in the rats after 4-week simulated weightlessness. However, there were no significant differences in the opening and closing rates of L-VDCs, the position of steady-state activation and inactivation curves, and in the parameters, V(0.5) and k, between either of the two groups and its respective control group. The membrane capacitance and the reversal potential of the VSMCs from the small mesenteric arteries of rats after simulated weightlessness also showed no significant changes. These findings suggest that the decreased function of the L-VDC in hindquarter VSMCs might be one of the electrophysiological mechanisms that mediate the depressed vasoreactivity and atrophic change in hindquarter arteries during adaptation to simulated weightlessness in rats.

Animals↗

Counteracting effect of head-up tilt on increased femoral venous compliance after simulated weightlessness in rabbits.

BACKGROUND: The increased femoral venous compliance is one of the factors of orthostatic intolerance after space flight. The purpose of this study was to observe the effect of daily head-up tilt (HUT) on stress-strain relationship of femoral vein during simulated weightlessness in rabbits. METHODS: Head-down tilt (HDT) 20 degrees rabbit model was used to simulate weightlessness. Twenty-four healthy male New-Zealand rabbits were randomly divided into three groups: simultaneous control, 21 d HDT, and 21 d HDT plus daily 2 h HUT 45 degrees, with 8 in each. Twenty-one days later, stress-strain relationship of femoral vein was examined. RESULTS: Under the same stress, the circumferential strain both in the 21 d HDT group and the 21 d HDT plus daily 2 h HUT group increased significantly than those in the control group. There were no significant differences between these two groups. There were no significant changes in the longitudinal strain among three groups under the same stress. CONCLUSIONS: The femoral venous compliance of rabbits increase significantly after 21 days simulated weightlessness. Daily 2 h HUT 45 degrees could not prevent increase of femoral venous compliance in rabbits induced by 21 days simulated weightlessness.

Adaptation, Physiological↗