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Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.

To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.

Adult↗

[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↗

[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 simulated weightlessness on phase II drug metabolism in the rat.

BACKGROUND: Exposure to weightlessness is known to alter physiological processes in humans and animals. As a result of these changes, hepatic drug metabolism may be altered as well. Indeed, short term simulated weightlessness in the rat has been shown to increase oxidative metabolism. HYPOTHESIS: Simulated weightlessness will increase Phase II drug metabolism in the rat during short-term tail suspension. METHODS: The tail-suspended rat model was used to simulate weightlessness. Rats were subjected to 1, 3, 7, or 10 d of tail-suspension in order to mimic the effect of exposure to a microgravity environment. One additional rat group was not suspended and served as a control. On the final day of the study, rats we administered a single intravenous bolus dose of acetaminophen 25 mg x kg(-1) through an implanted jugular catheter and serial blood samples were taken for 90 min. Serum acetaminophen concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters were determined by using standard model independent methods. RESULTS: The results show that simulated weightlessness in the rat has no effect on Phase II drug metabolism, using acetaminophen as a marker compound. CONCLUSIONS: These data support the hypothesis that simulated weightlessness in the rat modulates oxidative metabolism, but not drug conjugation to glucuronide or sulfate metabolites. These data offer insight into the physiological changes and variability seen in hepatic metabolic profiles in humans and animals following actual spaceflight.

Acetaminophen↗

[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 pressure-volume relationships of femoral vein of New Zealand Rabbits].

Objective. To observe the changes of pressure-volume relationships of rabbit femoral veins and their structural changes caused by simulated weightlessness. Method. Head-Down Tilt (HDT) -20 degrees rabbit model was used to simulate weightlessness. Twenty four healthy male New Zealand Rabbits were randomly divided into 21 d HDT group,10 d HDT group and control group, (8 in each group). Pressure-volume (P-V) relationship of rabbits femoral veins was measured and the microstructure of the veins was observed. Result. The femoral vein P-V relationship curves of HDT groups showed a larger volume change ratio than that of control group. This change was that 21 d HDT group was even more obvious than that of HDT-10 d group. B1 and B2 in quadratic equations of 21 d HDT group were significantly higher than the values of both 10 d HDT group and control group during expansion (inflow) and collapse (outflow) (P<0.01). The result of histological examination showed that the contents and structure of femoral vein wall of HDT-rabbits changed significantly. Endothelial cells of femoral vein became short and columnar or cubic, some of which fell off. Smooth muscle layer became thinner. Conclusion. Femoral venous compliance increased after weightlessness-simulation and the femoral venous compliance in 21 d-HDT rabbits increased more obviously than that in 10 d-HDT rabbits. The structure of femoral vein wall had changed obviously.

Adaptation, Physiological↗

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↗

Observation of the morphology and calcium content of vestibular otoconia in rats after simulated weightlessness.

Reduction in bone formation may have been the main reason for the lower calcium content of the otoconia after simulated weightlessness in rats. The head-ward distribution of blood volume may explain the morphological changes observed in the middle and inner ears. To observe morphological changes in the vestibular organs and measure the calcium content of otoconia in rats after simulated weightlessness. We used a tail suspension model of simulated weightlessness and then investigated changes in the vestibular organs using scanning electron microscopy and X-ray microanalysis. In comparison to untreated rats, the vestibular otoconia of the rats subjected to simulated weightlessness were small, irregularly shaped or fissured, and were arranged loosely and out of order. In addition, the calcium content of the otoconia was markedly decreased.

Animals↗

[Regulative effects of Chinese herb-compound on blood rheology and circulatory system of rabbits under simulated weightlessness].

OBJECTIVE: To investigate effects of Chinese herb-compound on blood rheology and circulatory system of rabbits under simulated weightlessness in order to provide bases for protecting against the influence of simulated weightlessness on cardiovascular function. METHOD: Rabbits were exposed to head-down tilt (HDT -20 degrees) for 9 d to simulate weightlessness. The effect of Chinese herb-compound on indices related to blood rheology, blood-fat and orthostatic tolerance in these rabbits were examined. RESULT: After head-down tilt, hematocrit value and red blood cells deformability decreased significantly; cholesterol and low density lipoprotein increased markedly; plasma fibrinogen content and triglyceride showed increasing trend. Administration of the Chinese herb-compound didn't improve the blood rheology indices, but showed a trend to decrease triglyceride and to inhibit the increase of cholesterol. In the head-up tilt (HUT) plus lower body negative pressure (LBNP) experiment, orthostatic tolerance time of the rabbits in the control group decreased, and myocardial ischemic changes in ECG, such as dropped ST segment, inverse T wave, and arrhythmia were observed. While in the Chinese herb-compound group, the heart rate of the rabbits kept smooth, ischemic changes in ECG were not clear, and orthostatic tolerance time increased. CONCLUSION: The Chinese herb-compound shows an effect of preventing orthostatic tolerance from decreasing, and improves blood-fat metabolism. It regulates different human systems on the whole, and increases ability of adaptation to ill environment.

Animals↗

Altered cytochrome P450 and P-glycoprotein levels in rats during simulated weightlessness.

BACKGROUND: In order to investigate the effects of simulated weightlessness on drug metabolism, liver, kidney, and small intestine, microsomal proteins from tail-suspended rats were analyzed to determine cytochrome P450 (CYP) and P-glycoprotein levels following varying durations of tail-suspension. HYPOTHESIS: P-glycoprotein and CYP levels would both decrease similar to previous findings from actual spaceflight data. METHODS: Six groups of four Sprague-Dawley rats each were tail-suspended for up to 21 d; CYP and P-glycoprotein levels in the liver, kidney and small intestine were then measured by Western blotting. The results were compared with a control group of unsuspended rats. RESULTS: Our data showed there were significant changes in the levels of hepatic CYP2C11, 2E1, 4A1, and P-glycoprotein and significant changes in the levels of P-glycoprotein and CYP4A1 in the kidney. However, there were no significant changes detected in the levels of CYP3A2 in the liver or small intestine. CONCLUSIONS: We conclude that simulated weightlessness, using the tail-suspended rat model, showed significant suppressive effects on levels of CYP2C11, 2E1, and P-glycoprotein in the liver and CYP4A1 in the kidney, while demonstrating no significant effect on the levels of CYP3A2 in the liver or small intestine. Thus, generalized predictions on the effect of simulated microgravity on drug metabolism cannot be made and the overall effect of spaceflight on individual enzymes should be investigated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Erythrocyte deformation in simulated weightless human and rabbits.

Effect and mechanism of simulated weightlessness (SWL) in humans and rabbits erythrocyte deformation were studied. Erythrocyte deformation and membrane fluidity in humans and rabbits, and erythrocyte morphology and hemorreology indices in control and HDT rabbits were measured. The results were a decrease in erythrocyte deformation and membrane fluidity in humans and rabbits during SWL, a significant increase in abnormal erythrocyte, blood viscosity, hematocrit, fibrinogen, and red blood cell aggregation index in HDT rabbits. These results show that the changes in erythrocyte shape, increase of erythrocyte internal viscosity and changes in erythrocyte visco-elasticity may be causing the decrease of erythrocyte deformation in SWL humans and rabbits.

Adolescent↗

Simulated weightlessness in the design and exploitation of a NMR-compatible bioreactor.

Mammalian cells cultured in simulated weightlessness take advantage of a favorable environment, experiencing low shear stress and reduced turbulence. NMR spectroscopy allows the on-line noninvasive monitoring of cell growth and metabolism. With this in mind, we developed a novel bioreactor that fits into a NMR instrument and in which the simulated weightlessness conditions are obtained by a suitable medium and a flow-lift suspension. In detail, the gravitational vector acting on cells is counterbalanced by the hydrodynamic thrusts created by a bottom-up spiral flow of a fluid having increased density. We validate its efficiency (a) by calculating the main physical parameters as relative velocity, shear stress, and oxygen transport, and (b) by comparing the experimental results of growing a cell culture in the proposed bioreactor with those obtained using an established simulated weightlessness system (rotating wall vessel, NASA). As a test study we focused on the proliferation of human umbilical vein endothelial cells (HUVEC) in terms of cell viability and organization of their cytoskeleton.

Bioreactors↗

[Effect of simulated weightlessness on the apoptosis of thymus cells in tail-suspended mice].

OBJECTIVE: To investigate the effect of simulated weightlessness on apoptosis of thymus cells in mice. METHOD: Tail-suspended mice were used as an animal model of simulated weightlessness; chromosome breakage was measured by PI staining, and changes of cell membrane were determined by Annexin-V analysis. RESULT: As compared with the control, there was no obvious chromosome breakage; the total number of apoptotic cells and number of early apoptotic cells increased in 1 d suspended group; the number of early apoptotic cells increased significantly and the total number of apoptotic cells increased very significantly in 2d suspended groups. CONCLUSION: These results suggested that simulated weightlessness could promote apoptosis of thymus cells.

Animals↗

[Effects of simulated weightlessness on vasoreactivity of hindlimb arterial bed in rats].

OBJECTIVE: To investigate the alterations in vasoreactivity of hindlimb arterial bed after simulated weightlessness. METHOD: The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoreactivity of arterial bed were examined in vitro using isolated, constant flow perfused hindlimb of 2-wk suspended rats and control rats. RESULT: Perfusion flow-pressure relationship of hindlimb arterial bed showed no significant differences between suspended rats and control rats; but vascular responses to KCl (20-100 mM) and PE(10(-8)-10(-4) M) were decreased in hindlimb arterial bed of suspended rats as compared with that of control rats. CONCLUSION: Contractile ability of resistance vessels was diminished in simulated weightlessness rats, and a compromised ability of resistance vessels to increase peripheral resistance may play an important role in occurrence of orthostatic intolerance.

Adaptation, Physiological↗

Adaptability of Japanese quail chicks to conditions of simulated weightlessness.

The objective of this study was to evaluate the adaptability of young Japanese quail chicks to the simulated weightlessness, represented by hypodynamy. Unsexed hatchlings were subjected to hypodynamy on either the first, second or third day of age and reared under these conditions to 21 days of age. During this period, the control quail chicks were housed in a floor box. The effect of hypodynamy on adaptability of chicks was significant (P < 0.001). Approximately 75% of all chicks exposed to hypodynamy were not able to adapt in three experimental groups, although significant differences in adaptability were not found between these groups. Those birds were considered as non-adapted (eliminated from experiment) that manifested hyperactivity, escape attempts, turning 180 degrees in the sling, soaking in the water from the drinker, as well as the total apathy, at least three times per day. This experiment confirmed that some quail chicks are capable of adapting to conditions simulating weightlessness to 21 days of age and that the first 2-weeks after hatching may be a critical period of quail sensitivity to hypodynamy. This finding raises a key issue relevant to rearing quails in simulated weightlessness until the age of sexual maturity.

Adaptation, Physiological↗

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Adaptation, Physiological↗

Plasma viscosity elevations with simulated weightlessness.

Bed rest studies which simulate weightlessness have demonstrated marked changes in the state of hydration of subjects as well as decrements in aerobic capacity. These two phenomena may be linked through increases in blood viscosity which is altered by a loss of free water and which, in turn, influences blood flow needed for aerobic muscular work. This study examines changes in the rheologic properties of blood which attend changes in plasma volume with bed rest in humans and correlates these changes with alterations in aerobic capacity. Eight healthy human subjects were studied on the 6th day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of shuttle astronauts. Plasma viscosity was measured with a Wells-Brookfield viscometer, plasma volume by dye dilution, and maximal aerobic capacity (VO2max) by recumbent cycle ergometry. Bed rest resulted in significant increases in hematocrit and in total plasma protein concentration and fibrinogen concentration, both of which contribute to an elevation in plasma viscosity. The greater than 20% increase in fibrinogen concentration was much greater than could be explained by hemoconcentration. VO2max decreased significantly in the first but not the second bed rest cycle. In many individuals, a decrease in plasma volume and aerobic capacity was coupled with elevated plasma viscosity and hematocrit; however, significant correlations between these variables were lacking. Although significant rheologic perturbations do occur with bed rest, in this study, blood viscosity elevation failed to directly correlate with the reduction in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of simulated weightlessness on pressure-volume relationships of femoral veins in vivo of New-Zealand rabbits.

OBJECTIVES: To observe the change of pressure-volume relationships of femoral veins of rabbits after simulated weightlessness. METHODS: Head-down tilt(HDT) -20 degrees rabbit model was used to simulate weightlessness .24 healthy male New-Zealand Rabbits were randomly divided into 21d HDT group, 10d HDT group and control group, with 8 in each. The pressure-volume relationships of rabbits femoral veins were measured. RESULT: The femoral vein P-V relationship curves of HDT groups were shifted to larger volume change ratio than that of control group. The P-V relationship curve of the 21d HDT group was shifted more obviously than that of HDT-10d. B1 and B2 in quadratic equations of 21d HDT group were significantly higher than these value of 10d HDT group and control group during expansion (inflow) and collapse (outflow) (P<0.01). CONCLUSIONS: The femoral venous compliance increased after weightlessness simulation and the femoral venous compliance of 21d-HDT increased more obviously than that of 10d-HDT.

Comparative Study↗