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Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths.

The effects of increased gravity in the head-to-foot direction (+G(z)) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He phase III slopes increased proportionally with increasing gravity, but the (SF(6) -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He slopes significantly but resulted in increased (SF(6) -- He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions.

Adult↗

Contractile properties of rat single muscle fibers and myosin and troponin isoform expression after hypergravity.

The effects of 19 days of hypergravity (HG) were investigated on the biochemical and physiological properties of the slow soleus muscle and its fast agonist, the plantaris. HG was induced by rotational centrifugation that led to a 2-G gravity level. The HG rats were characterized by a slower body growth than control, whereas the soleus muscle mass was increased by 15%. Using electrophoretic techniques, we showed that the distribution of myosin heavy chain and troponin T isoforms was not modified after HG in both soleus and plantaris. In contrast, the isoform expression pattern of two troponin subunits, troponin I and troponin C, was changed in a slow-to-fast manner only in the soleus. From tension-pCa relationships, changes in Ca(2+) activation threshold by 0.18 pCa unit indicated a decrease in Ca(2+) sensitivity and an increase in the slope of the curve, attesting to a higher cooperativity along the thin filament after HG. Comparison of our HG data with previous results in microgravity conditions indicated that muscle characteristics, except muscle mass, did not evolve linearly from 0 to 2 G.

Animals↗

Differential changes of lung diffusing capacity and tissue volume in hypergravity.

In normal gravity, lung diffusing capacity (DL(CO)) and lung tissue volume (LTV; including pulmonary capillary blood volume) change in concert, for example, during shifts between upright and supine. Accordingly, DL(CO) and LTV might be expected to decrease together in sitting subjects in hypergravity due to peripheral pooling of blood and reduced central blood volume. Nine sitting subjects in a human centrifuge were exposed to one, two, and three times increased gravity in the head-to-feet direction (G(z+)) and rebreathed a gas containing trace amounts of acetylene and carbon monoxide. DL(CO) was 25.2 +/- 2.6, 20.0 +/- 2.1, and 16.7 +/- 1.7 ml. min(-1). mbar(-1) (means +/- SE) at 1, 2, and 3 G(z+), respectively (ANOVA P < 0.001). Corresponding values for LTV increased from 541 +/- 34 to 677 +/- 43, and 756 +/- 71 ml (P < 0.001) at 2 and 3 G(z+). Results are compatible with sequestration of blood in the dependent part of the pulmonary circulation just as in the systemic counterpart. DL(CO,) which under normoxic conditions is mainly determined by its membrane component, decreased despite an increased pulmonary capillary blood volume, most likely as a consequence of a less homogenous distribution of alveolar volume with respect to pulmonary capillary blood volume.

Adult↗

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum.

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

Adaptation, Physiological↗

Simulated microgravity and hypergravity attenuate heart tissue development in explant culture.

Exposure to altered gravity may disturb the cytoskeleton-cell surface-extracellular matrix (ECM) interface of embryonic cells. Development of organs such as the heart depends on dynamic interactions across cell surfaces. Fibronectin (FN), for example, a glycoprotein that links the ECM to the cytoskeleton through integrin surface receptors, is required for normal heart development. Thus, altered gravity may perturb organogenesis. We cultured precardiac explants from chick embryos in a rotating bioreactor vessel to simulate microgravity (microG), or in a tissue culture centrifuge, for 18 h during heart development. Bioreactor microG did not alter external morphology of explants, but did significantly reduce the proportion that developed contractions. Immunostaining for FN of explant sections showed that it also significantly reduced the linear extent of staining present in basement membrane regions. Analysis of ultrastructure revealed a significant reduction in the number of desmosomes per unit area and other differences. Hypergravity dramatically abolished development of contractions and altered morphogenesis. The results indicate a probable sensitivity of cardiomyogenic development involving FN to altered gravity.

Animals↗

Effects of hypergravity environment on the parathyroid gland of the norepinephrine-treated golden hamster: a stereological study.

Effects of 5-gravity environment on the ultrastructure of the parathyroid glands of norepinephrine-treated golden hamsters were studied. In the centrifuged animals treated with norepinephrine, the volume density occupied by the Golgi complexes associated with numerous prosecretory granules was significantly increased compared with that of the control, centrifuged and norepinephrine-treated animals, as well as the volume density occupied by the cisternae of the granular endoplasmic reticulum compared with that of the control and centrifuged animals. In addition, in the centrifuged animals treated with norepinephrine, numerous secretory granules were situated close to the plasma membrane. It is suggested that the synthesis and release of secretory granules may be markedly stimulated in the parathyroid glands of the norepinephrine-treated golden hamsters subjected to a hypergravity environment.

Adrenergic alpha-Agonists↗

Hypergravity and aging in Drosophila melanogaster. 8. Proboscis-extension-response threshold to sucrose.

The proboscis extension response threshold to sucrose has been measured in young, middle-aged and old male Drosophila melanogaster flies living at a gravity level of 1, 3.02 or 5.02 g until the experiment. The threshold increased with age and no effect of gravity level was observed at any age. These data are at variance with those of previously studied behavioral traits which showed that flies living in hypergravity seemed to age faster than 1-g ones.

Aging↗

Effect of prolonged hypergravity on the vestibular system: a behavioural study.

Golden hamsters were exposed to conditions of 2.5 times normal gravity (hypergravity, HG) for 4 months. During this period, tests were carried out to study equilibrium maintenance, swimming behaviour and open-field behaviour of these HG hamsters and of control hamsters living in a normal-gravity environment. The tests proved to be useful devices for detecting differences in perceptive-motor behaviour between HG hamsters and control hamsters. The HG hamsters had more difficulties in balancing on tubes and orientation during swimming. In the open-field study, the HG hamsters showed less locomotor activity than control hamsters. However, no differences were observed between the groups in washing, rearing and number of times having defaecation. These findings indicate that the daily transition from 2.5 to 1 g was not experienced as stressful by the hamsters, although performance on several perceptive-motor tasks was decreased, especially during the first weeks.

Animals↗

Cyclic AMP-receptor responses to hypergravity.

BACKGROUND: Altered gravity (G) encountered during spaceflight causes physiologic changes in humans and in experimental animals. In addition to weightlessness (0G) in space, sharply increased G forces are exerted on the spacecraft during the lift-off and reentry phases. Previous studies showed major changes in cAMP-associated activity of rat heart muscle after spaceflight, indicating that (hormone) signaling pathways may have been affected. HYPOTHESIS: The present study was designed to test the hypothesis that cAMP-related cellular responses of exocrine glands after simulated hypergravity (centrifugation at 1.7G) differ from the effects of 0G. METHODS: A portion of the parotid and lachrymal gland tissue was fixed for morphologic and immunocytochemical study, and another was used for biochemical determinations. A short-term tissue culture was established from each gland to determine the effects of stimulation by norepinephrine. Heart muscle (ventricle) was also studied. Soluble and particulate fraction extracts of tissue homogenates were prepared, photoaffinity labeled with the [32P]8-N3-analog of cAMP, proteins separated by electrophoresis and the cAMP-reactive proteins (cARP) identified by autoradiography. RESULTS: Differences were seen in protein banding patterns of the gland extracts and in altered cARP distribution in the 1.7G samples of heart ventricle and exocrine gland tissues, when compared with 1G controls. In the heart, cARP increased in the soluble fraction, while the particulate fraction extract showed no change. In acinar cells of the parotid, labeled cARP had accumulated, but decreased after stimulation to the level of the 1G controls. Immunogold labeling showed an increased content of amylase in the secretory granules of the 1.7G animals, while morphologic observation revealed few changes in the structure of parotid acinar cells. The response in the lachrymal gland was translocation of an isoform of cARP from the particulate to the cytoplasmic compartment. CONCLUSIONS: Changes distinct from those due to 0G, but specific for hyper-G were found in cARP activity, protein synthesis, as well as in an apparent inhibition of regulated secretion.

Adaptation, Physiological↗

Hypergravity does not affect testicular function.

BACKGROUND: A previous study revealed that exposure of rats to microgravity for 14 d on Cosmos 2044 reduced production of testosterone by > 80%, although spermatogenesis remained essentially normal. METHODS: To ascertain if testicular function was altered in hypergravity, 60-d-old rats were randomly assigned to 2 groups (10 per group) and subjected to 14 d of centrifugation to expose them to a total of 2G, or held at unit gravity in similar cages without centrifugation (control). RESULTS: After 14 d, body weight of 2G rats was essentially unchanged, whereas that of control rats had increased; 310 vs. 377 g (p < 0.05). Testes weight, production and secretion of testosterone, diameters of seminiferous tubules and their lumina, data from subjective evaluation of spermatogenesis, and counts of homogenization-resistant spermatids all were similar for 2G and control rats. CONCLUSION: It was concluded that exposure of male rats to 2G for 14 d had no major effect on testicular function whereas, based on earlier studies, exposure to microgravity (< 10(-3) x gravity) for 11-14 d suppressed production of testosterone by Leydig cells and reduced concentrations of anabolic steroids available to peripheral tissues.

Animals↗

Effect of microgravity and hypergravity on embryo axis alignment during postencystment embryogenesis in Artemia franciscana (Anostraca).

Cysts of brine shrimp attached with a liquid adhesive to 12-mm diameter glass coverslips in a syringe-type fluid processing apparatus were flown aboard the NASA space shuttle Discovery, flight STS-60, from 3-11 February 1994, and were allowed to undergo postencystment embryogenesis and to hatch in microgravity. The shuttle flight and the ground-based control coverslips with attached cysts were parallel to the earth's surface during incubation in salt water. Based on the position of the cyst shell crack in the attached cyst population, the ground-control nauplii emerged mostly upward. On the shuttle in microgravity, although our method of detection of orientation would not reveal emergence toward the coverslip, the ratio of the position of the cyst shell crack in the population after hatching best fit the predicted values of a random direction for nauplii emergence. Centrifugation on earth was then used to create hypergravity forces of up to 73 g during postencystment embryogenesis and hatching. The upward orientation of emerging nauplii showed a high degree of correlation (r(2) =98.8%) with a linear relationship to the log of g, with 78.2% of the total hatching upward at 1 g and 91.0% hatching upward at 73 g.

Animals↗

Wound healing following injury to vascular smooth muscle cell cultures is modulated by culture under hypergravity.

Anticipated hazards for crewmembers in future long-term space flights may result in a variety of injuries including fractures, deep punctures or cuts. The microgravity environment of space may complicate the wound healing process. Myofibroblasts have been proposed to play a role in wound contraction; these cells develop from tissue fibroblasts sue fibroblasts develop numerous features found in vascular smooth muscle cells (SMC), ultrastructural features, expression of alpha-SM actin and microfilament bundles. These changes have been shown to be inducible by TGF beta 1. Previous studies have also shown that TGF beta 1 is capable of initiating and regulating critical events in bone fracture, soft tissue, dermal wound healing. Several studies have suggested that bFGF may also be involved in the wound healing process, and that the interactions of bFGF with TGF beta 1 control the overall repair of a wounded tissue. The formation (angiogenesis) and/or repair of blood vessels is also essential for wound healing. Both TGF beta 1 and bFGF have been shown to affect both angiogenesis and vascular injury repair. However, the response of cells following injury, in a microgravity or hypergravity (HG) environment has not been evaluated. We assessed the influence of HG (centrifugation at 6G) and clinostat rotation at 30 rpm (CR) on the response of SMC to a denudation injury. We also examined the possible involvement of c-myc, c-fos and TGF beta 1 in meeting the response of SMC to wounding.

Animals↗

Perception of the cabin attitude changes in hypergravity.

BACKGROUND: The G-excess illusion is becoming increasingly recognized as a cause of aviation fatalities. Studies of this illusion have looked at perception of subjects' orientation by moving the head during hypergravity, but independent of the pilot's head movement with respect to aircraft. This illusion can also occur by aircraft motion, but this has not been studied extensively. OBJECTIVE: The aim of this study was to investigate the subject's perception of orientation to the simulator cab attitude changes at 1.6 G without making any head movement with respect to the cab, and assess the feasibility of simulating the G-excess illusion on the ground with a centrifuge-like spatial disorientation simulator. METHODS: The 1.6-G force field was provided by the gravitoinertial force (GIF) of the simulator when it made an off-center (planetary) rotation at a constant velocity of 130 degrees x s(-1). Eleven subjects' perceptions of orientation of the cab attitudes were collected respectively by their report before and after certain cab tilt, in a roll plane of 1.6 G. RESULTS: When the cab was tilted 20 degrees at 1.6 G, the subjects perceived the angle to be 48.6 +/- 39.4 degrees. CONCLUSION: Most subjects experienced an exaggerated sensation to the cab attitude changes in roll plane. G-excess illusion can be generated in a centrifuge-like device on the ground.

Adult↗

The effects of hypergravity and substrate vibration on vestibular function in developing chickens.

We used linear vestibular evoked potentials (VsEPs) to characterize peripheral and central vestibular function in birds following embryogenesis at 2G centrifugation or at elevated levels of vibration (+20dB re: background levels). Additionally, we characterized peripheral and central vestibular adaptation to 2G centrifugation in early post-hatch birds. Linear VsEP response peak latencies, amplitudes, thresholds and input/output functions were quantified and compared between experimental and control animals. Birds vibrated throughout embryogenesis and up to one-week post-hatch revealed no changes in linear VsEP response components compared to control siblings. Birds centrifuged at 2G throughout embryogenesis also evidenced no changes in the linear VsEP measured at hatch (P0). Significant changes were seen, however, for linear VsEPs of post-hatch birds placed at 2G for 7 days beginning on post-hatch day 5. Linear VsEPs for these animals displayed significant reductions in response amplitudes associated with peaks P2, N2 and P3, response peaks generated by central neural relays of gravity receptors. The earliest response components, generated by the peripheral vestibular nerve (i.e., P1, N1), were not significantly altered with the 7-day exposure to 2G. Thus, there was no evidence of generalized changes in peripheral gravity receptor excitability or in the rate of maturation in developing animals under increased levels of gravity or vibration. If gravity level plays a critical role in shaping peripheral vestibular ontogeny at magnitudes between 1 and 2G, then it may serve to stabilize function under changing G-fields or it may operate on physiological features that can not be resolved by the VsEP. In contrast, exposure to elevated gravity during post-hatch periods does alter central vestibular function thus providing direct evidence for central vestibular adaptation to the gravitational environment. The fact that central functional change was observed in hatchlings and not embryos, raises the possibility that the first 2-weeks post-hatch may be a critical period of "heightened developmental sensitivity" to hypergravity.

Adaptation, Physiological↗

Testosterone urinary excretion rate increases during hypergravity in male monkeys.

Real and simulated microgravity impairs T secretion both in animals and in the human. To verify whether hypergravity might enhance T secretion as a consequence of an opposite mechanical effect, 6 male monkeys were centrifuged at 2 G for 3 weeks after a 1 G stabilization period lasting 3 weeks and then taken back to 1 G for 1 week and urine were collected daily for T excretion measurement. Significantly higher level were observed during the initial 2 G phase as compared to pre- and post centrifugation periods and the trend was the same during the remaining 2 G period. This may reflect changes in testicular perfusion rather than endocrine adaptation per se.

Animals↗

Hypergravity and aging in Drosophila melanogaster. 9. Conditioned suppression and habituation of the proboscis extension response.

In a first experiment, the conditioned suppression of the proboscis extension response (PER) to sucrose was measured in young, middle-aged and old male Drosophila melanogaster flies living at either 1, 3 or 5 g. Flies were starved and then subjected to a learning task involving a sucrose stimulus, followed by an aversive one applied to their forelegs. In this learning task, flies learn to not extend their proboscis when walking on sucrose. Flies which have lived in hypergravity (HG) had a lower number of PER suppressions than 1 g ones, and this finding was mainly due to young and middle-aged flies. In a second experiment, the habituation of the PER was studied using as stimulation sucrose solutions 2-fold (first experiment), 4-fold (second one) or 8-fold (third one) higher than the individual sucrose threshold. Middle-aged and old flies habituated more slowly than young flies in the second and third experiments. In the third experiment, a decreasing speed of habituation was observed when gravity increased; this result was mainly due to young flies, and no gravity effect was observed in the other two age groups. This whole set of results suggests that HG-kept flies do not age faster than 1 g ones, as far as these learning and habituation tasks are concerned. It seems possible that HG acts like a mild stress to which flies adapt; if applied for a long time, HG could induce a premature aging, as observed in the previous papers of this series.

Aging↗

Control of isometric force in hypergravity.

BACKGROUND: Previous work suggests that proprioceptive signals are degraded in hypergravity (hyper-G). We therefore, expected that production of finely graded force is disturbed as well. METHODS: Subjects produced isometric force with their thumb and index finger upon verbal instruction, before, during and after exposure to +1.5 Gz and +3 Gz. Produced force was orthogonal to the direction of gravity. RESULTS: In hyper-G, responses to a given target value were significantly higher (by about 400 pond) than in normal gravity, while the modulation of produced force with target force didn't change. The results in +1.5 Gz and +3 Gz were quantitatively similar, and a positive aftereffect was found. CONCLUSIONS: Subjects underestimate by a constant amount the force they produce in hyper-G. Our results are reminiscent of similar findings with pointing and grasping movements in hyper-G.

Adult↗

EMG activity of three rat hindlimb muscles during microgravity and hypergravity phase of parabolic flight.

BACKGROUND: In man, quantifications of the motor activity have mainly been performed to study changes in posture and locomotion after space-flight. On the contrary, physiological data relative to the motor activity have never been obtained in animals in real microgravity. HYPOTHESIS: The purpose of this study was to evaluate, in rats, the immediate effect of real microgravity on the neuromuscular activity of three hindlimb muscles. METHODS: Under aseptic conditions, the soleus (SOL), lateral gastrocnemius (LG) and tibialis anterior (TA) muscles of rat hindlimb were implanted each with a pair of electrodes. Their electromyographic (EMG) activity was analyzed before, during, and after parabolas, a parabola being composed of two 2 G episodes separated by one 0 G episode. Each episode lasted about 25 s. RESULTS: Our results showed that, when compared to normal gravity (1G), hypergravity increased the EMG activity in the ankle extensors SOL and LG, whereas microgravity immediately induced a redistribution in the motor activity between the two antagonists, SOL and TA. CONCLUSIONS: An immediate adaptation occurred in the motoneuronal recruitment of rat hindlimb muscles at the onset of changes in gravity level. This could be interpreted in terms of a short-term adaptative process involving peripheral mechanisms initiated by changes in activity of muscle spindles.

Adaptation, Physiological↗