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PubMed1995

The study on the mechanism of G intolerance of rabbits after simulated weightlessness.

The direct consequence of cardiovascular adaptation to weightlessness (WL) is the decrease of G tolerance. In studying the mechanism of G intolerance after WL, respiration, heart rate, electrocardiogram, temporal arterial flow, loss of vision were usually used as the indices for evaluation of G tolerance. However the changes of microcirculation and blood rheological indices were seldom observed. Considering that the changes of status of blood circulation after WL may be one of the important factors causing decrease of G tolerance, the purpose of this paper is to observe the changes of microcirculation, blood rheological and the structure and circulatory status of four organs in rabbits during -4Gx after exposure to simulated weightlessness (SWL), in order to understand the cause of G intolerance after WL.

Animals↗
PubMed2002

[Changes in potassium currents of vascular smooth muscle cells isolated from hindquarter arteries of rats after 4 weeks simulated weightlessness].

The changes in potassium currents of vascular smooth muscle cells (VSMCs) isolated from saphenous arteries and the 2nd-6th order branches of the mesenteric arteries of 4-week tail-suspended rats (SUS) were examined using whole cell patch clamp technique. The resting potential (RP) of the VSMCs from SUS group was more negative compared with that of the control group (CON).The whole cell potassium current densities of VSMCs isolated from the saphenous arteries and small mesenteric arteries in SUS group were significantly larger than those of the CON group.The BK(Ca) and K(V) current densities of VSMCs from saphenous arteries and small mesenteric arteries from SUS group were also significantly larger than those from the CON group.It is speculated that the hyperpolarization of VSMCs and decreased calcium influx through voltage-dependent calcium channels might be one of the electrophysiological mechanisms involved in the depressed vasoreactivity of hindquarter arteries induced by simulated weightlessness.

Animals↗
PubMed1997

Effects of simulated weightlessness on erythrocyte deformability in rats.

In order to investigate the mechanism of space anemia, the erythrocyte deformability membrane fluidity and cell shape in 7, 15, 30 day tail-suspended rats were observed. The results were: (1) erythrocyte deformability (DImax and IDI) in suspended rats was significantly lower than that in the control on the 7th day (P<0.05), and had a further decrease on the 15th day (P<0.01), but a recovery was found on the 30th day (P<0.05). (2) membrane fluidity in suspended rats was markedly lower than that in the control group on the 15th and 30th day, degrees of fluorescence polarization was increased (P<0.01), but there was no change on the 7th day. (3) percentage of erythrocytes with abnormal shape in suspended rats was higher than that in the control group during the whole experimental period. The results indicate that the changes of rheological and morphological properties of red cell were induced by simulated weightlessness (SWL), which may be an important cause of space anemia.

Anemia↗
PubMed1993

Cardiovascular deconditioning effects of long-term simulated weightlessness in rats.

The aim of our serial work was to investigate the cardiovascular deconditioning effect of long-term simulated weightlessness and to elucidate its mechanisms. Our research goal was established in view of the following three reasons. Firstly, even after several decades of extensive research, there still exist significant gaps in our knowledge concerning microgravity induced cardiovascular effect. Secondly, to guarantee the health and safety of astronauts in the future prolonged missions, it is important to understand the cardiovascular adaptation to long-term weightlessness. Thirdly, the reported ultrastructural degenerative changes in myocardium of rats flown on the Cosmos 1887 biosatellite has raised concerns about the question whether long-term spaceflight may lead to myocardial degeneration. To achieve this, we considered an appropriate animal model to simulate cardiovascular and other effects of long-term microgravity was of first importance. By making some modifications to the Morey-Holton's model, a method of long-term tail-suspension with less stressful influence and no injurious effects on the tail skin was developed. Up to now, the longest period of suspension in our laboratory has been of 120-day long. In this paper, we will focus primarily on the findings from our recent works on the cardiovascular deconditioning effect of 90-/120-day tail-suspension and changes in baroreflex responsiveness and in contractility and ultrastructure of the heart in rats.

Animals↗
PubMed1988

Leg vascular responsiveness during acute orthostasis following simulated weightlessness.

Ten men (35-49 years old) underwent lower body negative pressure (LBNP) exposures before and after 10 d of continuous 6 degrees head-down bedrest in order to predict the effect of weightlessness on the responsiveness of leg vasculature to an orthostatic stress. Heart rate (HR), mean arterial blood pressure (MAP), and impedance rheographic indices of arterial pulse volume (APV) of the legs were measured during rest and at 1 min of -30 mm Hg LBNP. Bedrest-induced deconditioning was manifested by decreases (p less than 0.05) in plasma volume (17%), peak oxygen uptake (16%), and LBNP tolerance (17%). Resting HR was unchanged after bedrest, but HR was higher (p less than 0.05) at 1 min of -30 mm Hg LBNP after, compared with before, bedrest. Responses of MAP to -30 mm Hg LBNP were not altered by bedrest. Resting APV was decreased (p less than 0.05) by simulated weightlessness. However, APV was reduced (p less than 0.05) from rest to 1 min -30 mm Hg LBNP by the same relative magnitude before and after bedrest (-21.4 +/- 3.4% and -20.5 +/- 2.7%, respectively). We conclude that peripheral arterial vasoconstriction, as indicated by reductions in APV during LBNP, was not affected by bedrest. These results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness. Therefore, it appears unlikely that control mechanisms of peripheral resistance contribute significantly to reduced orthostatic tolerance following spaceflight.

Adaptation, Physiological↗
PubMed1999

Effects of daily 2-Gz load on human cardiovascular function during weightlessness simulation using 4-day head-down bed rest.

An onboard short arm human centrifuge has been proposed as a countermeasure against physiological problems during long exposure to weightlessness in space and during extra planetary exploration. However, there are few studies on the effects of intermittent application of a Gz load via centrifuge during weightlessness. The present study evaluated the effects of a daily 2-Gz load on cardiovascular function during simulated weightlessness using a 4-day head-down bed rest (HDBR) period. Twelve young male subjects were exposed a HDBR period. Eight of them were exposed to a Gz load for up to 30 min twice per day (the Gz group). The remaining 4 were not exposed to a Gz load; they served as controls (the no-Gz group). Compared with the pre-HDBR period, the no-Gz group showed percent changes in the RR interval, the standard deviation (SD) of the RR interval, parasympathetic nervous activity, and baroreflex sensitivity (BRS) that progressively decreased and reached significance at the end of the HDBR period (-5.96 +/- 2.60%, -33.82 +/- 9.60%, -46.3 +/- 12.7% and -30.9 +/- 7.2%, respectively). In the Gz group, however, the percent changes in the RR interval, the SD of the RR interval, parasympathetic nervous activity, and BRS showed no significant changes throughout the HDBR period. At the end of the HDBR period, these indexes were 2.22 +/- 2.21%, -2.31 +/- 12.28%, 5.08 +/- 14.82% and 10.6 +/- 12.5%, respectively, and significantly greater than those of the no-Gz group. Sympathovagal balance indicators showed no significant change in the Gz and no-Gz groups (5.17 +/- 12.85% and 18.5 +/- 10.7%, respectively). These results indicate that a daily load of 2-Gz eliminates reduction of the RR interval, the SD of the RR interval, parasympathetic nervous activity, and BRS, and that it can maintain autonomic cardiovascular function in short-term weightlessness.

Adult↗
PubMed1992

Simulated weightlessness and bone metabolism: gravitational stimulation enhances insulin sensitivity.

The effect of simulated weightlessness on bone metabolism was investigated in skeletal unloading for 4 days. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading with hindlimb hang cased a significant decrease of alkaline phosphatase activity, deoxyribonucleic acid (DNA) content, and glucose consumption in the femoral diaphysis, but not in the calvaria. When femoral-diaphyseal tissues were cultured in the presence of insulin (10(-8) M), the hormone produced a significant increase of alkaline phosphatase activity and decrease of glucose consumption in the femoral-diaphyseal tissues obtained from normal rats. This hormonal effect was not seen in the femoral diaphysis, but in the calvaria, of rats with skeletal unloading. However, insulin effect was seen in the femoral diaphysis obtained at 3 days after the removal of skeletal unloading. Meanwhile, the presence of other bone-regulating factors (10(-8) M parathyroid hormone [1-34] and 10(-4) M zinc sulfate) revealed an appreciable effect on alkaline phosphatase activity in the femoral diaphysis from rats with skeletal unloading. These results suggest that gravitational stimulation can directly enhance a specific insulin sensitivity in the regulation of bone metabolism.

5'-Nucleotidase↗
PubMed1983

Recovery of the rat skeleton from the adverse effects of simulated weightlessness.

A rat model that involves total mechanical unloading of the hind limbs has been used to simulate some aspects of weightlessness. In a previous study, the presence of marked skeletal abnormalities in the proximal tibial and humeral metaphyses of unloaded rats was detected. In the current study, the rats were removed from the model after a 2-week suspension period and allowed to recover for 2 weeks in individual metabolic cages before sacrifice. Tetracycline derivatives were administered on three separate occasions to evaluate radial and longitudinal bone growth. Periosteal bone formation in the tibial diaphysis of suspended animals was significantly depressed during the suspension period but approached control levels during the recovery period. Periosteal bone formation in the humeral diaphysis was not affected by simulated weightlessness. In the proximal tibial and humeral metaphyses, longitudinal bone growth, the amount of mineralized tissue, and the fat content of the bone marrow, all of which were previously determined to be abnormal after 2 weeks of simulated weightlessness, returned to control levels during the recovery period. The previously observed decline in the osteoblast population and increased numbers of osteoclasts adjacent to the growth plate in suspended animals also proved to be reversible at both skeletal sites. This study demonstrates that the skeleton of growing rats is capable of a rapid recovery from the adverse effects of simulated weightlessness.

Animals↗
PubMed1991

Simulated weightlessness and bone metabolism: impairment of glucose consumption in bone tissue.

The effect of simulated weightlessness on bone glucose consumption was investigated in skeletal unloading for up to 4 days. Skeletal unloading was designed using the model of hind-limb hang in rats. Femoral-diaphyseal fragments obtained from rats bred with skeletal unloading were cultured for 24 h at 37 degrees C in 5% CO2/95% air in Dulbecco's Modified Eagle Medium (high glucose, 4.5 g/dl). The consumption of medium glucose by bone tissues was significantly decreased by skeletal unloading for 2 and 4 days, while the production of lactic acid from bone tissues was not significantly altered. In addition, adenosine triphosphate (ATP) content in the cultured bone was significantly decreased by skeletal unloading. The presence of calcitonin (synthetic [Asu1,7] eel, 3 and 30 nM) fairly restored bone glucose consumption impaired by skeletal unloading. However, the effect of insulin (1 and 10 nM) on bone glucose consumption and ATP content was not seen in the bone tissues with skeletal unloading. These results suggest that the sensitivity of bone response for insulin action is reteriorated by skeletal unloading.

Adenosine Triphosphate↗
PubMed1991

Changes in hepatic metabolism through simulated weightlessness: decrease of glycogen and increase of lipids following prolonged immobilization in the rat.

The effect of simulated weightlessness on hepatic metabolisms of carbohydrates and lipids was investigated in rats that were chronically immobilized by means of a suspension harness. During the 10-day period of the suspension, the animals showed a substantial decrease in the hepatic glycogen content, whereas the content of hepatic total lipids was markedly elevated. Similar results were obtained when the "suspended" animals were provided with a regular amount of nutrients by a force-feeding procedure. In the suspended animals, hepatic parenchymal cells were filled with large fat droplets, and hepatic triglyceride contents were elevated. The prolonged immobilization led to a slight, but significant, increase in glucose-6-phosphatase activity in the liver, suggesting that an increased glycogen breakdown might have occurred in the suspended animals. However, it was unlikely that the increased amount of glucose produced by the glycogen breakdown was utilized as a substrate for the lipogenesis in the liver, because hepatic lipogenic enzyme activities were unaffected by the suspension. The results suggest that the hepatic lipids accumulate in animals exposed to a prolonged immobilization state, presumably due to a decreased lipolysis and/or a suppressed lipoprotein mobilization from the liver into the blood stream.

Adrenal Glands↗
PubMed1991

Simulated weightlessness and bone metabolism: evidence for direct gravitational effect and its related insulin action.

The effect of simulated weightlessness on bone metabolism was investigated in skeletal unloading for 4 days. Skeletal unloading was designed using the model of hind-limb hang in rats. In hypokinetic state, rats were fed while the right hind limb was weighed down and the left hind limb was unloaded (a state of weightlessness). Bone metabolism in normal rats did not vary significantly in the femoral diaphysis in right and left hind limb. Alkaline phosphatase activity and DNA content in the femoral diaphysis were not significantly altered by hypokinetic state without skeletal unloading, while the unloading caused an appreciable decrease in the enzyme activity and DNA content. However, femoral-diaphyseal zinc content and glucose consumption was significantly decreased by hypokinetic state with and without skeletal unloading. When femoral-diaphyseal tissues were cultured in the presence of insulin (10 nM), the hormone produced a significant increase of alkaline phosphatase activity and decrease of glucose consumption in the femoral-diaphyseal tissues obtained from normal and hypokinetic rats. This hormonal effect was not seen in bone tissues from hypokinetic rats with skeletal unloading. These results suggest that skeletal unloading-induced disorder of bone metabolism is directly related to gravitational effect and that gravitational stimulation may be involved in insulin action.

Alkaline Phosphatase↗
PubMed1991

Simulated weightlessness and bone metabolism: impairment of insulin effect on alkaline phosphatase activity in bone tissue.

The effect of simulated weightlessness on bone alkaline phosphatase was investigated after skeletal unloading for up to 4 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The femoral-diaphyseal fragments obtained from rats bred with skeletal unloading were cultured for 24 h at 37 degrees C in 5% CO2/95% air in Dulbecco's Modified Eagle Medium (high glucose). The bone alkaline and acid phosphatase activity were significantly decreased by skeletal unloading. When the bone tissue was cultured with synthetic [Asu1,7] eel calcitonin (3 and 30 nM), the hormone caused a significant increase of alkaline phosphatase activity in the bone tissues from rats with normal and skeletal-unloading. In culture with insulin (1.0 and 10 nM), skeletal unloading impaired the effect on insulin to increase bone alkaline phosphatase activity. Meanwhile, the culture with zinc sulfate (10 and 100 microM), which can increase bone protein synthesis, caused a remarkable elevation of alkaline phosphatase activity in the bone tissues form rats with normal and skeletal-unloading. Insulin (10 nM) did not alter the zinc effect. These findings suggest that the skeletal unloading with hindlimb hang causes the impairment of insulin's effect to increase alkaline phosphatase activity in the femoral diaphysis of rats, although the effects of calcitonin and zinc were not altered.

Alkaline Phosphatase↗
PubMed1989

Simulated weightlessness and bone metabolism: decreases of protein and DNA syntheses in the femoral diaphysis of rats.

The effect of simulated weightlessness on bone protein and DNA syntheses was investigated in the skeletal unloading for up to 4 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The femoral-diaphyseal fragments obtained from rats which bred with skeletal unloading were cultured for 3 h at 37 degrees C in 5% CO2/95% air in Dulbecco's Modified Eagle Medium (high glucose). When the bone tissues were pulsed with [3H]proline, the incorporation of [3H]proline into the bone protein was significantly decreased by skeletal unloading. In the pulse with [14C]uridine, the incorporation of [14C]uridine into the bone RNA was significantly reduced by skeletal unloading. Moreover, the incorporation of [3H]thymidine into the acid-insoluble residues of bone tissue was significantly decreased by skeletal unloading. Also, DNA content in the femoral diaphysis was significantly reduced by skeletal unloading. These findings suggest that skeletal unloading causes the decreases of protein and DNA syntheses in the femoral diaphysis of rats.

Animals↗
PubMed2003

Influence of simulated weightlessness on the oral pharmacokinetics of acetaminophen as a gastric emptying probe in man: a plasma and a saliva study.

This study evaluated the effect of simulated weightlessness on gastric emptying, using acetaminophen as a probe and -6 degrees head-down bed rest to simulate zero gravity. Eighteen volunteers were given 1 g of acetaminophen orally before the bed rest and at days 1, 18, and 80. Cmax, tmax, AUC0- infinity, AUC0-t, and t1/2 were calculated for plasma and saliva. The plasma Cmax showed a significant increase (10.43 microg/mL [day 1] to 14.74 microg/mL [day 80]), while tmax significantly decreased (1.41 h [day 1] to 0.91 h [day 80]). Similar results were obtained with saliva, and there were significant increases in the AUCs. The good correlation between the plasma and saliva data suggests that saliva sampling can be valid for acetaminophen pharmacokinetics. The changes in Cmax and tmax indicated more rapid drug absorption, which could have been as a result of faster gastric emptying or an increased blood flow to the intestine.

Acetaminophen↗
PubMed2000

Validation of the doubly labeled water method in rats during isolation and simulated weightlessness.

Total energy expenditure (TEE) of rats during simulated microgravity is unknown. The doubly labeled water method (DLW) reliably measures TEE, but the results depend on the methods of calculation. These methods were validated and appraised by indirect calorimetry in eight rats during isolation (7 days) and simulated microgravity (10 days). There were no effects on CO(2) production in the method used to derive constant flux rates as in the regression models. r(CO(2)) estimates were dependent on the assumed fractionation processes, the derivation of constant flux rate methods, and the selected pool models. Use of respiratory or food quotients did not influence TEE estimations, which were similar during isolation and simulation. During either isolation with growth or simulation with a stabilized mass, the one-pool model of Speakman (Speakman JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) resulted in the more reliable validation (0.8 +/- 2.2 and 2.2 +/- 3.4% vs. calorimetry, respectively). However, during simulation, agreement was also observed with the single pool model of Lifson (Lifson N, Gordon GB, and McClintock R. J Appl Physiol 7: 704-710, 1955) (-2.5 +/- 2.5%), and two two-pool models [Schoeller (Schoeller DA. J Nutr 118: 1278-1289, 1988) (0.5 +/- 3.1%) and Speakman (Speakman, JR. Doubly Labelled Water. Theory and Practice. London: Chapman and Hall, 1997) (-1.9 +/- 2.7%)]. This latter finding seems linked to the stable body mass and to fractionation consideration close to the single-pool model of Speakman. During isolation or simulated microgravity, the other equations underestimated TEE by 10-20%.

Animals↗
PubMedDate not supplied

[Paramecium test for toxic substances in the blood of humans exposed to conditions simulating weightlessness].

The Paramecium test was for the first time used to measure the build-up of toxic substances in the healthy man exposed to simulated weightlessness. The most distinct changes were seen on bed rest days 3 and 7-8 in all test subjects (41 subjects). After bed rest day 8 the parameter reached a plateau, the toxicity level stopped to increase, but the Paramecium test time remained shorter than normal. It can therefore be suggested that the prognosis of any disease that may develop in this situation will be worse. In view of this it is important to improve the prophylaxis and treatment of endogenous and exogenous intoxications during space flight and to provide active detoxication based on the purification of biological fluids by sorption.

Adult↗
PubMed1979

Ultrastructural development of the vestibular system under conditions of simulated weightlessness.

Electronmicroscopy was used to track the development of the gravity system of frog embryos and larvae which have bred for 5, 7, and 10 d after egg fertilization under conditions of simulated weightlessness on the fast-running horizontal clinostat. Although no differences in the morphologic structure of the organ between test and control animals could be found up to 7 d of development, there is a significant accumulation of vacuoles in sensory epithelia of frog larvae develpoping for 10 d (stage 17) in simulated zero G.

Animals↗
PubMed2003

Effects of periodic weight support in a simulated weightless environment in preventing bone demineralisation.

Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.

Animals↗