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PubMed1999

[Effects of 7 d head-down tilt (-20 degrees) immobilization on pharmacokinetics of gentamicin in rabbits].

OBJECTIVE: To observe pharmacokinetic changes under simulated weightlessness in relevant to body flood flow changes. METHOD: Gentamicin was selected as probe drug in the present study, and rabbits exposed to Head-Down Tilt (HDT, -20 degrees) immobilization were selected as simulated weightlessness animal model. Seven rabbits were treated inf. with 3 mg/kg of gentamicin sulfate pre-HDT and 7 d after HDT. Gentamicin blood samples within 4 h after administration were analyzed by TDxFLx. RESULT: The distribution of gentamicin postponed significantly: a significant decrease in alpha from (0.1838 +/- 0.1076) min-1 before HDT to (0.0591 +/- 0.0334) min-1 after HDT; a significant increase in t1/2 alpha from (5.30 +/- 3.55) min to (15.04 +/- 7.49) min; a significant decrease in k12 from (0.1025 +/- 0.0721) min-1 to (0.0181 +/- 0.0161) min-1, a increase trend in V(C) and V(D). After HDT, CL(S) of gentamicin increased from (2.2 +/- 0.5) ml min-1 kg-1 to (2.7 +/- 0.3) ml min-1 kg-1. CONCLUSION: Simulated weightlessness might induce pharmacokinetic changes.

Adaptation, Physiological↗
PubMed2001

Changes of human cerebral bottom arterial hemodynamics during 21 d head-down tilt (-6 degrees) bed-rest.

OBJECTIVE: To investigate the change of human cerebral bottom arterial hemodynamics during 21 d simulated weightlessness. METHOD: 21 d -6 degrees head-down tilt bed rest (HDT) were used to simulate weightlessness. 6 healthy male, aged 24.8 +/- 6.1 served as subjects. Systolic blood velocity (Vs), diastolic blood velocity (Vd), mean blood velocity (Vm), pulsatility index (PI), resistance index (RI) and other indices of middle cerebral arteries (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA) were measured by transcranial ultrasound Doppler before HDT and on day 0 (D0), 1, 3, 7, 10, 21 of HDT. HUT +75 degrees 20 min orthostatic tolerance tests were done on day -1, 10, and 21 of HDT. RESULT: During HUT +75 degrees 20 min orthostatic tolerance test on day 10 and 21 of HDT, the average standing time were shorter than that of the pre-HDT values (P<0.05). On day 3 and 21 of HDT, Vs of right MCA reduced significantly than pre-HDT (P<0.05 or P<0.01). On day 1, 3, 7, 10 and 21 of HDT, Vs of right MCA were obviously lower than that on D0 (P<0.05 or P<0.01). Left MCA Vs on D0 increased significantly than that of pre-HDT (P<0.05), and both were significantly higher than those of the 3rd day of HDT (P<0.01). Right MCA Vm on the 3rd and 21st day of HDT were significantly lower than those pre-HDT and D0 (P<0.05 or P<0.01). On day 10 of HDT, Vm of right MCA were significantly reduced than that on D0 (P<0.05). Both MCA bilateral velocity difference (right Vm-left Vm) on the 3rd, 10th, 21st day of HDT, and MCA inter-hemispheric asymmetry index on the 10th, 21st day of HDT were significantly lower than that of pre-HDT (P<0.05 or P<0.01). CONCLUSION: 21 d HDT bed-rest decreased orthostatic tolerance, Vs of both side MCA, and Vm of right MCA. Lower Vs of both side MCA and the inter-hemispheric asymmetry of MCA during HDT maybe responsible, in part, for the increased risk of orthostatic intolerance.

Adaptation, Physiological↗
PubMed2003

[Effects of 7 d head-down bed rest on human vectorcardiogram (VCG)].

OBJECTIVE: To study the effects of short-term simulated weightlessness on human vectorcardiogram (VCG). METHOD: Seven d -6 degrees head-down bed rest (HDBR) was used to simulate weightlessness. Eight healthy males, aged 19-21, served as the subjects. VCG was recorded before and on day 1, 3, 7 of HDBR. RESULT: QRS loop in the horizontal plane rotated counterclockwise, while QRS loop in the right sagittal plane rotated clockwise during HDBR (P<0.05 or P<0.01). QRS-T angle in the horizontal and right sagittal plane increased significantly during HDBR. CONCLUSION: Seven d HDBR leads to changes of VCG parameters, which were all in normal ranges and in accordance with the volume changes of atrium and ventricle, but obviously different from those resulted from pathological ventricular thickening and myocardial ischemia.

Adult↗
PubMed1993

Early amphibian (anuran) morphogenesis is sensitive to novel gravitational fields.

Anuran amphibian embryos (Xenopus laevis and Rana dybowskii) are sensitive to novel gravitational fields. Under simulated weightlessness, (i) the location of the first horizontal cleavage furrow was shifted toward the vegetal pole at the eight-cell stage; (ii) the position of the blastocoel was more centered, and the number of cell layers in the blastocoel roof was increased at the blastula stage; (iii) the dorsal lip appeared closer to the vegetal pole at the gastrula stage; and (iv) head and eye dimensions were enlarged at the hatching tadpole stage. Effects of simulated hypergravity were opposite to those of simulated weightlessness, except that hypergravity, unlike simulated weightlessness, reduced the number of primordial germ cells in feeding tadpoles. Despite those dramatic differences in the early embryogenesis, tadpoles at the feeding stage are largely indistinguishable from controls.

Animals↗
PubMed1995

Muscle strength during bedrest with and without muscle exercise as a countermeasure.

Bedrest is known to be a useful experimental model for simulating weightlessness and studying its effects on human skeletal muscle activity. We therefore conducted a study in which 12 healthy male subjects underwent 28 days of continuous exposure to 6 degrees head-down bedrest. Our main objective was to test a set of preventive countermeasures for maintaining the stability of the human body. Of the subjects 6 performed deadlifts in the supine position for 30 to 45 min each day. The isometric actions were performed for 5-30 s at 90, 120 and 150 degrees knee angles and isokinetic training at speeds of 30 and 180 degrees.s-1. In vivo quadriceps muscle strength was measured under controlled experimental conditions with a commercial dynamometer. The hypothesis that intense daily isometric and isokinetic leg exercise and lower body negative pressure (LBNP) might serve to maintain muscle strength under conditions of weightlessness was tested. Of the subjects 6, who did not perform any exercise, served as the control population under conditions of simulated weightlessness. The results showed that a significant reduction (P < or = 0.0001) in the muscle force [-10.3 (SD 6.7%)] occurred in the control group whereas no significant changes were observed in the trained group [+3.9 (6.8%)]. From these studies we conclude that intense muscle training and LBNP constitute efficient countermeasures to compensate for the biomechanical effects of weightlessness on human lower limbs and to limit other factors such as cardiovascular deconditioning.

Adult↗
PubMed1976

Human tolerance to acceleration after exposure to weightlessness.

The major role in the genesis of varying human tolerance to decelerations that follow weightlessness is evidently played by hypodynamic and hydrostatic factors. Long disuse of compensatory antigravity mechanisms in weightlessness may bring about their deconditioning and reduction of their functional capabilities, and may finally affect general tolerance of crewmembers to decelerations. Laboratory experiments demonstrated changes in the human tolerance to Gx accelerations of varying duration (from 3 to 100 days) and tested the efficacy of different countermeasures. A decrease in the human tolerance to +Gx is on the average -2.0g. It should be noted that an elongation of simulated weightlessness (from 7 to 100 days) caused no further decrease in the +Gx tolerance. Our investigations helped to assess the threshold of human tolerance to accelerations after an exposure to simulated weightlessness and to delineate the value of real risk. The tolerance limit to +Gx accelerations which followed simulated weightlessness of the above duration ranged from 9.5 to 13.0g, averaging 11.6 +/- 1.6g. The information on the tolerance of Soviet and American astronauts to decelerations shown during re-entry in real space flights give support to the laboratory results and predictions.

Acceleration↗
PubMedDate not supplied

[The acceleration of ultrastructure changes of synapses in somatosensory cortex of the rats at repeated simulation of weightlessness effects].

The electronmicroscopica/study of brain somatosensory cortex in the rats, exposed to postponed for a long time repeated lack of support load on hindlimbs by means of tail-suspension, has been revealed in hindlimb area of cortex the changes of ultrastructure of axodendritic synapses and neurons pointing out the acceleration of decrease in functional activity of synapses and neurons in 3-4 layers at postponed for a long time repeated simulation of weightlessness effects.

Animals↗
PubMed1999

Relatively shorter but intensive isotonic exercise in legs prevented the decrease in maximal aerobic power after 20 days of head down tilt bed rest in man.

As a countermeasures for the decrease in maximal oxygen uptake (VO2max) during prolong simulated weightlessness, it has been suggested that intensive isotonic legs exercise was useful. The reason is possibly that a dynamic and intensive resistance exercise training makes to maintain not only the volume of exercising muscles but also cardiac output. For the reason, it has been studied the effects of 3 different exercise training on VO2max during simulated weightlessness.

Bed Rest↗
PubMed1995

Antipyrine pharmacokinetics in the tail-suspended rat model.

As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greater concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our study was to examine the effects of simulated weightlessness on the pharmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total of 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day-1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated weightlessness. In addition, clearance was elevated after 1 day of tail-suspension in the p.o. dosing group. Steady-state volume of distribution was not statistically different over the entire study period in either dosing group. Data from the present study suggest that brief periods of tail-suspension may markedly alter the pharmacokinetics of drugs in the rat and that more studies are required in models of weightlessness and actual space flight to understand the complex interaction between microgravity and hepatic metabolic activity.

Administration, Oral↗
PubMed1994

The location of the third cleavage plane of Xenopus embryos partitions morphogenetic information in animal quartets.

Analysis of the developmental potential of animal quartets (the set of four animal blastomeres isolated from the 8-cell stage Xenopus embryo) provided insight into the manner in which morphogenetic information is distributed along the animal-vegetal axis. Gravity treatments were employed to alter the partitioning plane. Animal quartets isolated from embryos exposed to simulated weightlessness had larger animal blastomeres, and they formed structures such as a groove and a protrusion more often than 1g-control animal quartets. Animal quartets with an unusual non-horizontal third cleavage plane were also found to have a higher frequency of protrusion formation than animal quartets with a typical horizontal cleavage plane. The increase in the frequency seen in simulated weightlessness animal quartets was not due to their increased size. Fusing two animal quartets isolated from hypergravity (3g) exposed embryos (small blastomeres and low incidence of protrusions) did not affect the frequency of protrusion formation. Molecular analyses revealed that a partial induction was associated with the protrusion formation. Transcripts of the dorsal lip specific homeobox gene, goosecoid, and alpha-cardiac actin were detectable by PCR amplification in the animal quartet with a protrusion, and alpha-cardiac actin mRNA was found by whole-mount in situ hybridization to be localized in the protrusion. Taken together, all these results are consistent with the notion that both animal and vegetal information is necessary for normal development and the partitioning of morphogenetic information into animal quartets results in gravity-dependent differential morphogenesis and gene regulation.

Actins↗
PubMed2002

[The changes of cardiovascular response to orthostatic stress caused by hypovolemia induced by weightlessness: a simulation study].

We introduced the method of computer simulation in the studies of gravitational physiology. Based on work of Melchior (1994), we developed a mathematical model that can be used to stimulate cardiovascular responses to orthostatic stress (lower body negative pressure, LBNP). The model includes 7 sub-models: the redistribution of blood, the filling of left ventricle, left ventricle working, peripheral circulation, control of heart rate (HR), control of peripheral resistance and control of venous tone. Then we simulated the changes of blood pressure (BP) and heart rate during lower body negative pressure, and the results agreed well with the results of our human experiment. By using the developed model, we also simulated the effects of hypovolemia on the BP, HR and shock index during orthostatic stress. The simulation results indicate that the cardiovascular responses to orthostatic stress change significantly when the decrease of blood volume is more than 15% of the total blood volume. However, if the amount of the decrease of blood volume is less than 5% of the total blood volume, HR and BP could be maintained in normal range by the regulation of baroreflex during LBNP. Our simulation results suggest that hypovolemia may be the main cause of orthostatic intolerance induced by weightlessness.

Adult↗
PubMed1992

Identification of specific gravity sensitive signal transduction pathways in human A431 carcinoma cells.

Epidermal growth factor (EGF) activates a well characterized signal transduction cascade in human A431 epidermoid carcinoma cells. The influence of gravity on EGF-induced EGF-receptor clustering and early gene expression as well as on actin polymerization and actin organization have been investigated. Different signalling pathways induced by the agents TPA, forskolin and A23187 that activate gene expression were tested for sensitivity to gravity. EGF-induced c-fos and c-jun expression were decreased in microgravity. However, constitutive beta-2 microglobulin expression remained unaltered. Under simulated weightlessness conditions EGF- and TPA-induced c-fos expression was decreased, while forskolin- and A23187-induced c-fos expression was independent of the gravity conditions. These results suggest that gravity affects specific signalling pathways. Preliminary results indicate the EGF-induced EGF-receptor clustering remained unaltered irrespective of the gravity conditions. Furthermore, the relative filamentous actin content of steady state A431 cells was enhanced under microgravity conditions and actin filament organization was altered. Under simulated weightlessness actin filament organization in steady state cells as well as in EGF-treated cells was altered as compared to the 1 G reference experiment. Interestingly the microtubule and keratin organization in untreated cells showed no difference with the normal gravity samples. This indicates that gravity may affect specific components of the signal transduction circuitry.

Calcimycin↗
PubMedDate not supplied

[Chief methods of modeling the biological effects of weightlessness].

The paper describes basic principles related to weightlessness simulation. In ground-based experiments zero-g is simulated with respect to the conceptual mechanisms of weightlessness effects on the body. The main components of the effects are considered to be elimination of deformations and fluid redistribution. The paper surveys and summarizes different methods of weightlessness simulation. It discusses advantages and disadvantages of water immersion, prolonged bed rest, hypokinesia, suspension in special devices with many degrees of freedom, walking on a treadmill at different angles, etc. The paper describes simulation of accentuated individual effects of zero-g during an exposure to longitudinal acceleration. It presents experimental physiological methods of simulation and symptoms of zero-g effects under normal laboratory conditions. The paper emphasizes inadequate use of some simulation techniques.

Bed Rest↗
PubMed2001

[Effects of vitamin K on bone metabolism in tail-suspended rats].

Objective. To study the effects of vitamin K on bone metabolize in simulated weightlessness rats. Method. Male SD rats were divided into three groups (n = 9): the free active control (FAC), the tail-suspended control (SC), and the tail-suspended group treated with vitamin K (SVK) (50 mg/kg weight/d). The experiment lasted for 3 weeks. Bone biomechanical properties, bone mineral contents (BMC) and bone biochemical markers of bone metabolism were determined. Result. Compared with SC, total and bound bone gla protein (BGP) of serum, BMC of the femur and tibia, femoral mechanical properties, ALP activity of tibia all increased significantly; while NO content of femoral trunk decreased significantly. Conclusion. Vitamin K improved the bone metabolism and bone structure, decreased bone loss, increased bone biomechanical properties, decreased catagmatic fatalness. It proved that vitamin K prevented bone loss of simulated weightlessness rats.

Alkaline Phosphatase↗
PubMed2002

[Effects of head-down bedrest on surface temperature distribution and non-evaporative heat dissipation].

OBJECTIVE: To study effect of simulated weightlessness on non-evaporative heat dissipation from different parts of the human body. METHOD: Body surface temperature distribution of five subjects was measured under -6 degrees head down bedrest for 7 d with HR-II infrared thermography. Non-evaporative heat dissipation was calculated with the heat exchange equations based on surface temperature. RESULT: The temperature difference between torso and extremities increased during bed rest, and the largest was 6.7 degrees C higher than the control on the 3rd day of bed rest. The part of non-evaporative heat dissipation from the torso increased about 6% and that from head-neck increased 2%. At the same time, the parts of heat dissipation from the upper and lower extremities decreased about 3% and 5% respectively. CONCLUSION: The parts of non-evaporative heat dissipation from different areas of the human body changed during simulated weightlessness. This result provided a basis for the flow distribution design of liquid cooling garment of EVA suit.

Arm↗
PubMed1997

Effect of gravity changes on the cyanobacterium Synechocystis sp. PCC 6803.

The impact of hypergravity and simulated weightlessness were studied to check whether cyanobacteria perceive changes of gravity as stress. Hypergravity generated by a low-speed centrifuge increased slightly the overall activity of dehydrogenases, but the increase was the same for 90 g and 180 g. The protein pattern did not show qualitative alterations during hypergravity treatment up to 180 g. Cells of Synechocystis PCC 6803 subjected to common stressors like salt, heat, and light clearly accumulated at least four general stress proteins (25, 31, 34, and 63 kDa, respectively). Three of these proteins could also be detected after hypergravity, but in such small amounts that their occurrence could only be taken as a weak indication of stress. Low-molecular-weight stress metabolites were not synthesized in response to hypergravity, indicating that this gravity change was unable to activate the osmotic signal transduction chain. Gravity-dependent alterations were observed only during simulated weightlessness (generated by a fast-rotating clinostat). The glutamate/glutamine ratio was significantly shifted toward a higher glutamine portion. Altogether, the results may indicate that moderate changes of gravity were hardly, if ever, sensed as stress by cyanobacteria.

Acceleration↗
PubMed2002

[Effects of 21 d -6 degrees bed rest on diastolic function of human left ventricle].

Objective. To investigate the effects of head down bed rest (HDBR), the simulated weightlessness, on the diastolic function of human left ventricle, and to discuss its role in cardiovascular deconditioning after space flight. Method. Six healthy young volunteers were subjected to -6 degrees HDBR for 21 d. Ultrasound Doppler technique was used to examine the changes of the diastolic function before, on the 10th, and 21st day during and 2nd day after HDBR. The orthostatic tolerance was also tested before and after HDBR. Result. Peak E-wave velocity (PEV) , peak A-wave velocity (PAV) , and velocity total integration of E-wave (VTI E), were significantly decreased (P<0.05) on the 10th and 21st day during and the 2nd day after HDBR, and velocity, total integration of A-wave (VTI A), ratio of E/A, and ratio of VTI E/A were also decreased, but did not reach the significant level (P>0.05). None of the six subjects passed the orthostatic tolerance test after HDBR. Conclusion. Simulated weightlessness can induce marked decline in diastolic function of human left ventricle.

Adolescent↗
PubMed2000

Aerobic exercise as a countermeasure for microgravity-induced bone loss and muscle atrophy in a rat hindlimb suspension model.

BACKGROUND: Loss of bone and skeletal muscle atrophy resulting from non-weight-bearing are major concerns associated with microgravity environment and spaceflight deconditioning. The objective of this research was to address the fundamental issue of whether bone loss and muscle atrophy could be attenuated using weight-bearing aerobic exercise on a treadmill as a countermeasure in rats subjected to simulated weightlessness by hindlimb suspension. METHOD: Bone and muscle from control and hindlimb-suspended groups with and without exercise were evaluated by bone mineral density (BMD), mechanical tests, bone histomorphometry and muscle mass. RESULTS: Femoral BMD of hindlimb-suspended (HS) rats subjected to treadmill exercise was significantly greater than femoral BMD of HS rats without exercise and also was equivalent to that of weight-bearing controls. Muscle mass from HS rats exercised on a treadmill was significantly greater than muscle mass from HS rats that did not exercise. Exercise did not result in muscle mass equal to that of controls, however. In addition, histomorphometric analysis of the metaphysis of the proximal tibia revealed that HS rats that exercised did not maintain bone formation equivalent to controls. No other bone parameters were found to vary significantly between groups. CONCLUSIONS: It was concluded that moderate aerobic exercise on a treadmill did attenuate bone loss and muscle atrophy due to simulated weightlessness by hindlimb suspension, however its effectiveness differed by tissue, anatomical site and parameter investigated.

Animals↗