[Regulation of hemodynamics during simulation of the transition to weightlessness (mathematical modelling)].
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Blood Volume↗
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[Circulatory and hormonal changes induced by microgravity].
The absence (or decrease) of the hydrostatic pressure during space flights (microgravity state) or simulations of weightlessness (by immersion, bed rest or head-down tilt) result in a body fluid shift and an engorgement of the central circulation where mechanoreceptors involved in plasma volume regulation are located. Their activation induces the initial (first hours) hormonal response with a decrease in plasma vasopressin, renin and aldosterone and probably an increase in a natriuretic factor (Gauer reflex). Prolonged exposure to microgravity leads to more complex and often hypothetical responses: cardiovascular deconditioning, modifications in secretion and circadian rhythms of above cited hormones. After 24 years of studies on approximately 200 astronauts our knowledge of cardiovascular and hormonal adaptation to space flight is still at the beginning.
Adaptation, Physiological↗
Tolerance of females to +GZ centrifugation before and after bedrest.
Because women may be included as passengers in the proposed Space Shuttle System, this study was designed to investigate the +GZ tolerance of women and the possible degradation of this tolerance after a period of weightlessness as simulated by bedrest. Twelve healthy Air Force Flight Nurses served as test subjects. Over a 1-week period, each subject was exposed to +GZ levels starting at +2 GZ and increasing by 0.5 GZ increments to a gray-out point. This point was determined by peripheral vision loss with a standard lightbar and by reverse blood flow in the temporal artery. Ultimately, each woman was subjected to three runs at the +3 GZ level; each run was approximately 55 min long, separated by 5-min rest periods. Eight subjects with the best tolerance times were selected for 14 d of bedrest in a horizontal position; the other four were ambulatory controls. Tests before bedrest, immediately following, and 5 d later showed that average +GZ tolerance decreased by 67% after bedrest.
Adult↗
Effects of hypovolemia and posture on responses to the Valsalva maneuver.
INTRODUCTION: We tested the hypotheses that hypovolemia would result in attenuated elevation in blood pressure, greater baroreflex-mediated tachycardia, and reduced capacity for vasoconstriction during a Valsalva maneuver (VM). METHODS: Heart rate (HR) and mean arterial pressure (MAP) were measured beat-by-beat before strain, during a 15-s VM strain at 30 mmHg expiratory pressure, and post-strain. Eight subjects performed three VM trials in each of three postures (supine, sitting, and standing) under two experimental conditions (normovolemic and hypovolemic). Hypovolemia was acutely induced by a bolus injection of 30 mg furosemide. Each experimental condition was conducted on a different day, separated by one week. delta MAP was used in analyses of phase I, late phase II (an indicator of vasoconstriction) and phase III of VM. The ratio delta HR/delta MAP, an index of nonspecific baroreflex control of HR, was used in analysis of early phase II and phase IV of the VM. RESULTS: Compared to normovolemia, hypovolemia resulted in 12% lower plasma volume (p = 0.0001). delta MAP for both phase I and phase III of the VM differed between postures (p = 0.0132 and p = 0.0003, respectively) and was lower in the hypovolemic condition than in the normovolemic condition for phase I in the standing posture (-5 mmHg, p = 0.0385). CONCLUSIONS: HR and blood pressure responses to alterations in intrathoracic pressure are affected by fluid redistribution (posture change), but not by circulating blood volume. Therefore, our results did not support our hypothesis that hypovolemia would result in attenuated elevation in blood pressure, greater baroreflex-mediated tachycardia, and reduced capacity for vasoconstriction during a Valsalva maneuver. However, moderate hypovolemia can be specifically predicted by the phase I response to a VM performed in the standing posture.
Adult↗
Alterations in skeletal muscle microcirculation of head-down tilted rats.
The head-down tilted whole body suspended (HDT/WBS) rat is recognized as a model that reproduces many of the responses seen during exposure to microgravity including an increase in systemic blood pressure. Functional alterations of microscopic blood vessels (arterioles) in skeletal muscle (cremaster muscle) were assessed for their role in the observed elevations of blood pressure associated with HDT/WBS. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine and vasodilation to nitroprusside were assessed in control rats, rats suspended for 7 or 14 days, and rats allowed to recover for 1 day after 7 days of HDT/WBS. Using in vivo videomicroscopy, neither baseline diameters nor ability to dilate were altered by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This study of the intact microvasculature of skeletal muscle reveals an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests that an elevated peripheral resistance in skeletal muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.
Animals↗
Pointing at memorized targets during prolonged microgravity.
BACKGROUND: Watt et al. (15) and Young et al. (17) have demonstrated that during prolonged microgravity, large errors can be made when pointing at memorized targets in the absence of vision. However, those experiments could not distinguish between errors caused by not knowing where the arm was pointed and errors caused by not knowing target location. The primary goal of this study was to determine the relative contribution of each of these potential sources of error. HYPOTHESIS: It was hypothesized that pointing errors would be greater than pre-flight controls if vision was continuously absent during testing, but not greater than pre-flight if vision was restricted only while pointing. METHODS: Five subjects on Spacelab SLS-2 (Part A) pointed at targets while keeping their eyes closed continuously; (Part B) touched various body parts and estimated the position of their arms while the eyes remained closed; and (Part C) pointed at the same targets as in A but closed their eyes only while pointing. RESULTS: On the ground, if the eyes were closed only while pointing, pointing errors averaged 4.5 degrees. After several days n space, errors averaged 7.0 degrees (p < 0.05). Again on the ground, if the eyes were closed continuously while pointing, an additional error of 4.0 degrees was measured. However, after several days in space, the additional error was 10.5 degrees (p < 0.0005). CONCLUSIONS: The results of this study suggest that the major problem encountered when pointing at memorized targets in microgravity is a lack of knowledge of target, not limb, position.
Adaptation, Physiological↗
Compact compliance chamber design for the study of cardiac performance in microgravity.
A need was identified for a Mock Circulation System (MCS) of small size and weight that could function in a microgravity environment for the investigation of cardiovascular response to the weightlessness of space flight. Part of the MCS development involved the redesign of the compliance chamber from a Penn State MCS using a coil spring instead of the leaf spring system employed in the Penn State system. The new compliance chambers achieve a weight reduction of 47% and a volume reduction of 64% over the original Penn State design. Testing showed the coil spring compliance chambers retained physiologic characteristics and adjustability by using coil springs of various stiffness, and functioned equivalently to the original Penn State design.
Biomechanical Phenomena↗
[Attenuation of the efficacy of vasoconstrictive effects in rats after a 3-week suspension].
Male Wistar rats were maintained suspended by the skin of posterior third of the back for three weeks. Constrictive reactions to norepinephrine and irritation of sympathetic nerves were studied with hindlimb vessels perfused with physiological solution at constant pressure. Perfusion pressure was stabilized at 40, 80, and 120 mmHg. During complete relaxation of the vascular smooth muscles the volumetric rate of perfusate flow in experimental animals was reduced comparing with their controls. This implies narrowing of the lumen in resistive vessels caused by suspension. Following suspension, reaction of rat's nerves to irritation was markedly lower than in the control at all levels of pressure. At 40 mmHg vessels of the suspended rats were more sensitive to norepinephrine; however, at 80 and 120 mmHg vascular sensitivity to the agent was reduced in the test group vs. the control. Suppression of the reactivity of hindlimb vessels to the constrictive agents may be one of the causes of failure of mechanisms of blood redistribution following prolonged gravitational deloading.
Animals↗
[Study of nontraditional neuromediator nitric oxide in paraventricular nuclei of the rat hypothalamus in extreme conditions].
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Animals↗
Comment on venoconstrictive thigh cuffs.
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Fluid Shifts↗
Arterial pressure in humans during weightlessness induced by parabolic flights.
Results from our laboratory have indicated that, compared with those of the 1-G supine (Sup) position, left atrial diameter (LAD) and transmural central venous pressure increase in humans during weightlessness (0 G) induced by parabolic flights (R. Videbaek and P. Norsk. J. Appl. Physiol. 83: 1862-1866, 1997). Therefore, because cardiopulmonary low-pressure receptors are stimulated during 0 G, the hypothesis was tested that mean arterial pressure (MAP) in humans decreases during 0 G to values below those of the 1-G Sup condition. When the subjects were Sup, 0 G induced a decrease in MAP from 93 +/- 4 to 88 +/- 4 mmHg (P < 0.001), and LAD increased from 30 +/- 1 to 33 +/- 1 mm (P < 0.001). In the seated position, MAP also decreased from 93 +/- 6 to 87 +/- 5 mmHg (P < 0.01) and LAD increased from 28 +/- 1 to 32 +/- 1 mm (P < 0.001). During 1-G conditions with subjects in the horizontal left lateral position, LAD increased compared with that of Sup (P < 0.001) with no further effects of 0 G. In conclusion, MAP decreases during short-term weightlessness to below that of 1-G Sup simultaneously with an increase in LAD. Therefore, distension of the heart and associated central vessels during 0 G might induce the hypotensive effects through peripheral vasodilatation. Furthermore, the left lateral position in humans could constitute a simulation model of weightlessness.
Adult↗
Distribution of 3H-nicotine in rat tissues under the influence of simulated microgravity.
Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness. The present study was conducted in the head-down-tilt (HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30 degrees for two weeks on a 12/12 light/dark cycle. During this period, body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected i.v. with a solution containing 4 microcuries of nicotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain, blood, trachea, salivary gland, lung, heart, esophagus, spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determined and calculated as percent of total injected radioactivity. Final body weights of suspended animals were significantly (P < 0.05) lower than those of controls (309 +/- 21 vs 350 +/- 11 g). 3H-Nicotine was retained in greatest amounts by the kidneys, followed in order by salivary glands, spleen, and gastrointestinal tissues. Compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues: esophagus (25%), aorta (25%), fundus (25%), trachea (22%), adrenals (18%), spleen (17%), and pancreas (12%). The decreased retention of nicotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differences in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.
Animals↗
Cell morphological, ontogenic, and genetic reactions to 0-g simulation and hyper-g.
Organisms use gravity for spatial orientation, and differentiation into species during evolution follows geological processes which are caused by gravity. On the other hand, the task of most organismic functions which have or may have a relation to gravity is to compensate gravity. Furthermore, today it is very obvious that organisms do not disintegrate under the conditions of weightlessness, at least for the currently tested durations. These previous statements indicate a large field of still unknown regulation and adaptation mechanisms. Experiments to simulate weightlessness on the fast clinostat and with hyper-g show a highly developed ability of the genetic chain and of differentiating cells in being autonomous against mechanical stresses caused by outer accelerations. Nevertheless, different strong and slight changes of different tested end points were found. The question remains if the cells react actively or only passively.
Animals↗
Alterations in calcium homeostasis and bone during actual and simulated space flight.
The weightlessness experienced in space produces alterations in calcium homeostasis. Gemini, Apollo, and Skylab astronauts exhibited a negative calcium balance due primarily to hypercalciuria. In addition, the bone mineral density of the calcaneus declined by approximately 4% in Skylab crew members after 84 d of orbital flight. The negative calcium balance and loss of calcaneal bone mineral in normal adults subjected to prolonged bed rest was comparable to that observed in space. The pathogenesis of bone loss during space flight and bed rest is not well understood due to the lack of histomorphometric data. It is also uncertain whether osteoporotic changes in astronauts are corrected postflight. The observed bone loss would be reversible and of no long-term consequence if the only abnormality was an increased remodeling rate. However, altered bone cell activity would probably result in irreversible bone loss with the premature development of senile osteoporosis many years after space flight. The main skeletal defect in growing rats placed in orbit aboard Soviet Cosmos biosatellites appears to be diminished bone formation. Bone resorption was not elevated during weightlessness. Although cortical bone returned to normal postflight, the decline in trabecular bone mass was somewhat persistent. These studies established that the modeling of a growing skeleton was altered in a weightless environment, but do not necessarily imply that a remodeling imbalance occurs in adults during space flight. However, various forms of simulated space flight inhibited bone formation during both skeletal modeling and the remodeling of adult bone.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A study on gene expression of angiotensin receptors in arteries from tail-suspended rats].
Objective. To investigate whether simulated microgravity [correction of microgravtiy] can result in alterations of mRNA expression of angiotensin receptors in rat arteries. Method. Rats were divided into simulated microgravity group and synchronous control group. Simulated microgravity rats were subjected to tail-suspension for 4-wk to simulate the effect of weightlessness. Result. Results from RT-PCR demonstrated that mRNAs of angiotensin II receptors, AT1a, AT1b, and AT2 were expressed in carotid arteries, abdominal aorta and femoral arteries, whereas only mRNAs of AT1a and AT1b were expressed in basilar arteries. There were no significant differences between the simulated-microgravity and control rats in the expression of mRNAs of AT1a, AT1b, and AT2 in these arteries. Conclusion. Angiotensin II receptors may play no regulatory role in the occurrence of the differentiated vascular adaptation during simulated microgravity.
Adaptation, Physiological↗
Application of physiologically based pharmacokinetic models for assessing drug disposition in space.
Exposure to weightlessness induces physiologic changes that may lead to pharmacokinetic and pharmacodynamic alterations of drugs administered to crew members in flight. Preliminary data from flight and ground-based studies indicate that pharmacologically significant changes occur in the kinetics of medications given in weightlessness and in simulated microgravity (head-down bed rest). Conducting flight studies on all available medications to identify the changes in their pharmacokinetic behavior in weightlessness is not feasible. An alternative approach for obtaining such information is to use computer simulations employing physiologically based pharmacokinetic (PBPK) models. Information thus obtained would be helpful in predicting the therapeutic effectiveness of medications in space, and also in developing plans for flight studies. This paper presents a brief review of relevant physiologic factors and pharmacokinetic implications of space flight, and includes a preliminary PBPK model for estimating plasma concentration-time profiles of acetaminophen under different experimental conditions.
Acetaminophen↗
Simulated microgravity induced damage in human retinal pigment epithelial cells.
PURPOSE: The goal of this study was to determine the potential damage to the human retina that may occur from weightlessness during space flight using simulated microgravity. METHODS: Human retinal pigment epithelial (hRPE) cells were cultured for 24 h in a National Aeronautics and Space Administration-designed rotating wall bioreactor vessel to mimic the microgravity environment of space. Single-stranded breaks in hRPE DNA induced by simulated gravity were measured using the comet assay. In addition, the production of the inflammatory mediator prostaglandin E2 (PGE2) was measured in these cells 48 h after recovery from simulated microgravity exposure. RESULTS: Simulated microgravity induced single-stranded breaks in the hRPE DNA that were not repaired within 48 h. Furthermore, PG E2 production was dramatically increased 48 h after the initial microgravity-induced damage, indicating the induction of an inflammatory response. There was less DNA damage and no PGE2 release in hRPE cells pretreated with the antiinflammatory agent cysteine during their exposure to microgravity. CONCLUSIONS: We have demonstrated that the microgravity environment generated by a NASA-designed rotating wall bioreactor vessel induces an inflammatory response in hRPE cells. This system thus constitutes a new model system for the study of inflammation in the retina, a system that does not involve the introduction of an exogenous chemical agent or supplementary irradiation. This in vitro method may also be useful for testing novel therapeutic approaches for suppression of retinal inflammation. Furthermore, we suggest a safe prophylactic treatment for prevention of acute, transitory, or enhanced age-related permanent blindness in astronauts or flight personnel engaged in long-haul flights.
Anti-Inflammatory Agents↗
Interpersonal relationships in isolation and confinement: long-term bed rest in head-down tilt position.
The long-term bed-rest was organized by ESA and CNES, in order to simulate the physiological effects of weightlessness: eight volunteers had to stay 42 days in bed, in a head down tilt position (-6 degrees). There were two subjects in a room, they could not be alone and it was difficult for them to have their own personal space and intimacy. In these circumstances, as in outer space, interpersonal relationships were of prime importance. This situation enabled us, through systematic observation, to analyze the evolution of the relational behavior in dyads, and to quote some social indicators of adaptation. Results show significant withdrawal, and the time spent alone was marked by the emergence, during the experiment, of specific preferential activities. Behavioral contagion was observed in each dyad (people engaged in the same activities at the same time), except in the one case of abandon. Moreover, the highest rates of inactivity and withdrawal were noted in this case. Verbal indicators were useful to comment these results and showed that, for all the dyads, one of the two subjects always played a regulating role by expressing a very positive perception of the situation. These results emphasize the importance of psycho-sociological factors in isolation and confinement. Thus, it appears that different modalities of interpersonal relationships, and not only verbal interactions, play a significant role in adaptation to stress situations.
Adaptation, Psychological↗