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PubMed1986

[Effects of weightlessness on phosphorus and calcium metabolism and bone remodeling].

Weightlessness results in negative calcium balance which can only reflect a redistribution of calcium in the body: the loss of calcium in the faeces and/or urine is constant, but an increase in urinary hydroxyproline indicating bone collagen destruction is not always detectable; moreover, a slowing down of collagen maturation may be suspected. Bone analysis by histomorphometry in animals and by indirect, non-invasive methods in man shows a decrease in bone mass. However, this bone tissue atrophy might only reflect excessive ageing of the bone during weightlessness, as suggested by slow bone formation and lack of variation in bone resorption. Since the experimental results obtained in men and animals during simulated weightlessness on earth are not strictly identical with those observed in space- flights, their validity may be questioned. Additional studies (notably histomorphometric studies) are therefore required for a better knowledge, as well as prevention, of the problems raised by human life in space.

Animals↗
PubMed1986

The temporal response of bone to unloading.

A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with 45Ca and [3H]proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more 45Ca and [3H]proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading. We believe that this cycle of inhibition and resumption of bone formation has profound implications for understanding bone dynamics during space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Animals↗
PubMed2002

Energy expenditure and blood flows in thermoregulatory organs during microgravity simulation in rat. Emphasis on the importance of the control group.

Rat tail suspension is commonly used to mimic human physiology in space. However, energy metabolism adaptation and related autonomic responses are unknown. To give new insights in energy homeostasis, we determined total energy expenditure (TEE) and blood flow redistribution in thermoregulatory organs during suspension using two control groups of animals widely accepted in the literature: the individually housed (isolated) and restraint rats (horizontally attached to the suspension device). Rats (n=33) were randomly assigned during 14-days to three experimental groups: isolated, suspended, or attached. TEE was assessed by a doubly labeled water method throughout the 14 days, and regional blood flow by radiolabeled microsphere procedure at the end of the protocol. Attachment vs. suspension resulted in a significant decrease in TEE (25%), skin (54%), adrenal (55%) and kidney (42%) blood flows, cardiac index (33%), and plasma corticosterone (50%), whereas total peripheral resistances increased (50%). Isolation vs. attachment triggered an inverse response, of similar amplitude, for all above variables. By comparing isolation and suspension, no overall effect was observed. The striking conclusion of this study is that no clear conclusion can be drawn. The choice of the isolated or attached animals as control profoundly influences the outcome results regarding the effects of simulated weightlessness. Further studies are needed but we favor the attached group as the true control since, from a theoretical point of view, a suspended rat is attached plus suspended. In such conditions, TEE decreases to the same extent in rat and humans during simulated microgravity. When reviewing published experiments, we recommend special attention to the control group used rather than on the effects of suspension as compared to an undefined control.

Animals↗
PubMed1993

Swimming velocity of Paramecium under the conditions of weightlessness.

During the 6 min-lasting "free-fall conditions" (4 x 10(-6) g) of the parabolic flight of a sounding rocket Paramecium aurelia cells showed an increase of 7.5 % in their mean swimming velocity. A detailed analysis revealed that the kinetic response was transient: after 3 min the velocity decreased to the speed of the former horizontal swimming at 1 g. Control experiments simulating the influence of vibration and hypergravity during launch of the rocket lead to the conclusion that the increase of the velocity during the parabolic flight was exclusively induced by the transition to 0 g. An increased velocity was also observed under the condition of simulated weightlessness on a fast-rotating clinostat microscope.

Acceleration↗
PubMedDate not supplied

[Use of the method of selective catheterization of the heart and major vessels in biomedical research with the participation of healthy persons].

The paper discusses the application of direct techniques to the study of circulation--catheterization of the heart and central vessels in biomedical experiments with the participation of healthy volunteers and during examinations of pilots, athletes, etc. The experiments showed high informativeness and reliability of the techniques and demonstrated their applicability to the study of gravity effects on the circulation and metabolism of different organs of healthy men as applied to aerospace and clinical medicine. These investigations allow clinical modelling of hemodynamic and metabolic changes that may develop in various organs and tissues in weightlessness, development of pathogenetically substantiated countermeasures against its adverse effects, formulation of certain requirements for artificial organs whose function should be as close as possible to that of natural organs of a healthy man. The paper presents the protocol and results of the first study of the effects of short-term simulated weightlessness on the circulation and metabolism of various organs of a healthy man: brain, heart, lungs, liver, kidneys, and musculoskeletal formations of the lower limbs.

Blood Circulation↗
PubMed2004

Skeletal muscle gene expression in space-flown rats.

Skeletal muscles are vulnerable to marked atrophy under microgravity. This phenomenon is due to the transcriptional alteration of skeletal muscle cells to weightlessness. To further investigate this issue at a subcellular level, we examined the expression of approximately 26,000 gastrocnemius muscle genes in space-flown rats by DNA microarray analysis. Comparison of the changes in gene expression among spaceflight, tail-suspended, and denervated rats revealed that such changes were unique after spaceflight and not just an extension of simulated weightlessness. The microarray data showed two spaceflight-specific gene expression patterns: 1) imbalanced expression of mitochondrial genes with disturbed expression of cytoskeletal molecules, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein, and 2) up-regulated expression of ubiquitin ligase genes, MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of muscle protein degradation. Distorted expression of cytoskeletal genes during spaceflight resulted in dislocation of the mitochondria in the cell. Several oxidative stress-inducible genes were highly expressed in the muscle of spaceflight rats. We postulate that mitochondrial dislocation during spaceflight has deleterious effects on muscle fibers, leading to atrophy in the form of insufficient energy provision for construction and leakage of reactive oxygen species from the mitochondria.

Adaptor Proteins, Signal Transducing↗
PubMed1991

Bone histomorphometric comparison of rat tibial metaphysis after 7-day tail suspension vs. 7-day spaceflight.

Using histomorphometric analysis, we compared the effects of 7 d spaceflight (Biocosmos 1667) and 7 d tail-suspension in tibiae of 12-13 weeks old male Wistar rats. The skeletal alterations induced by both true and simulated weightlessness in the proximal tibial metaphysis consisted of an inhibition of longitudinal growth as indicated by the reduction of the primary spongiosa thickness. In both primary and secondary spongiosae, the loss of trabecular bone was more extensive in flight rats than in suspended rats. Impairment in cancellous and endocortical osteoid surfaces occurred in microgravity and 1-G conditions but with greater magnitude in the spongy space in flight rats. In suspended rats, the cancellous mineralization rate was decreased, suggesting an alteration of the formation activity. Bone resorption remained unchanged in flight rats whereas a twofold increase occurred in simulated conditions. These data support the hypothesis that mechanisms of bone loss in space are not entirely identical to those of tail-suspension model on Earth. New experiments allowing comparison between actual spaceflight and spaceflight simulations must be developed in order to explore common alterations and to understand differential mechanisms in the bone system.

Animals↗
PubMed1994

The role of artificial gravity in the exploration of space.

Terrestrial animals including the human require regular periodic gravitational (g) stimulation to maintain normal physiologic functions on earth or in space. Identical g stimulations can be produced in space with inertial forces (G) using a centrifuge. These stimulations may be made more efficient in preventing physiologic deconditioning by increasing G levels above 1 G. The effective operational use of the centrifuge in space to prevent physiologic deconditioning from microgravity exposures will require ground-based studies using weightless simulation such as bedrest or dry immersion with laboratories that have human-use centrifuges. The use of periodic, increased-G exposures in space may offer a practical inexpensive solution in preventing physiologic deconditioning.

Aerospace Medicine↗
PubMed2005

The influence of weightlessness on pharmacokinetics.

The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail-suspension performed with animals and long-term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head-down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.

Animals↗
PubMed2002

Mitochondrial adaptations in skeletal muscle cells in mammals exposed to gravitational unloading.

It is known that exposure to actual or simulated weightlessness is often accompanied by decreased muscle dynamic performance, and increased level of blood lactate accumulation. Decreased mitochondrial content found in fibers of the working muscles is considered to be one of the possible causes for those changes. Studies on oxidative potential of the muscle cell (i.e. capacity of the cell to oxidative energy production) under conditions of altered gravity have been carried out since late 70-ties. It was shown that the relatively short term spaceflight and hindlimb suspension induced significant decrease oxidative enzyme activities and mitochondrial volume density in rat fast muscle. However postural soleus muscle failed to exhibit similar changes, although the absolute mitochondrial content was found to be sufficiently lower after exposure to simulated microgravity. This phenomenon allowed to conclude that the pronounced soleus fiber atrophy masked the proportional absolute decrease in oxidative potential which failed to be revealed as subsequent changes in mitochondrial volume density and oxidative enzyme activity. It is also important, that biosatellite studies exposed considerable changes in mitochondria distribution pattern inside m. soleus fibers: volume density of mitochondria (and, correspondingly, activity of oxidative enzymes) increases (or does not change) in the center of fiber, and decreases at its periphery, in subsarcolemmal area. However the time course of mitochondrial alterations development (particularly during long-duration exposures to real or simulated microgravity) and some peculiarities of the mitochondria distribution were not described yet. Also, materials dealing with simultaneous time-course comparative analysis of mitochondrial characteristics and indices of physiological cost of submaximal exercise are very rare. The present paper is purposed to compare the data, obtained in several experimental studies, allowed to analyze the possible contribution of muscle mitochondria changes to changes in metabolic cost of submaximal exercise and the time-course dynamics of mitochondrial characteristics under conditions of actual or simulated gravitational unloading.

Journal Article↗
PubMed1988

Effect of antiorthostatic bed rest on hepatic blood flow in man.

Physiological changes that occur during exposure to weightlessness may induce alterations in blood flow to the liver. Estimation of hepatic blood flow (HBF) using ground-based weightlessness simulation models may provide insight into functional changes of the liver in crewmembers during flight. In the present study HBF, indirectly estimated by indocyanine green (ICG) clearance, is compared in 10 subjects during the normal ambulatory condition and antiorthostatic (-6 degrees) bed rest. Plasma clearance of ICG was determined following intravenous administration of a 0.5-mg.kg-1 dose of ICG to each subject on two separate occasions, once after being seated for 1 h and once after 24 h of head-down bed rest. After 24 h of head-down bed rest, hepatic blood flow did not change significantly from the respective control value.

Adult↗
PubMed2003

Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins.

UNLABELLED: Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Alkaline Phosphatase↗
PubMedDate not supplied

[Kidney function and the glucocorticoid activity of the adrenal cortex during immersion].

The paper presents the study of renal and adrenal function in six normal men during and after 3-day water immersion used as weightlessness simulation. The renal excretion of fluid, basic electrolytes, creatinine and total 17-hydroxycorticosteroids (17-HOCS) for 24 hours and following a provocative water-load test (20 ml/kg) was measured. During the first post-immersion day diuresis increased by 77%, excretion of sodium by 42%, 17-HOCS by 43% and creatinine by 34% as compared to the pre-immersion level. Potassium excretion remained essentially unchanged. The circadian rhythm of excretion of the above substances was normal: at night the excretion decreased and in the morning increased noticeably. The study of renal function and adrenal activity was carried out 56 hours after the beginning of water immersion, using a provocative water-load test. Water excretory and osmoregulatory functions of kidneys, and glucocorticoid activity of adrenals remained normal. These data give evidence that during a 60 hour exposure to water immersion no functional hypocorticism develops.

17-Hydroxycorticosteroids↗
PubMed1988

Early hormonal effects of head-down tilt (-10 degrees) in humans.

The aim of this study was to determine the effects of a 5-h weightlessness simulation (using supine bed rest or head-down tilt at -10 degrees = HDT) on plasma renin activity (PRA), aldosterone (PA), and catecholamines (epinephrine-E, norepinephrine-NE, and dopamine-DA) and to compare the results with those obtained with horizontal bed rest (BR), which is often taken as a control situation for simulation studies. Ten healthy young volunteers submitted to the three following postural tests: 7 h sitting; 1 h sitting, 5 h supine, and 1 h sitting; 1 h sitting, 5 h HDT, and 1 h sitting. Our results show that a 5-h HDT or BR induced a significant progressive increase in plasma volume (14.5% for HDT and 7% for BR) and a decrease in diastolic blood pressure (18% for HDT and 17% for BR), PRA (60% for HDT and 40% for BR), PA (63% for HDT and 60% for BR), and NE (20% for HDT and 25% for BR) compared to the sitting position. E decreased only in HDT, and DA was unchanged. We concluded that the main part of the cephalad shift is achieved by bed rest as reflected by changes in hematocrit and plasma protein concentration. The decrease in diastolic blood pressure, the inhibition of the renin-angiotensin aldosterone system (in part explained by a decrease in NE) are similar in BR and HDT. We demonstrate that the use of a relevant body position as control is a major concern when investigating the hormonal effects of HDT. If recumbency is chosen as the control situation in HDT studies, it is not surprising to observe only few changes when HDT is applied.

Adrenal Medulla↗
PubMed2006

Human cerebral autoregulation before, during and after spaceflight.

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.

Adaptation, Physiological↗
PubMed1994

Sleep and circadian rhythms in space.

This paper presents a detailed critical review of the knowledge accumulated in the last three decades concerning research on sleep, work-rest schedules, and circadian rhythms in space. The focus of the paper is preceded by a brief review of the basic principles of the human circadian system and the physiology of the sleep-wake cycle, relevant to understanding the problem of astronaut work-rest scheduling. Much of what is known is based on anecdotal reports, mission log books, and debriefing of astronauts after flights. The broad literature reviewed, which includes studies from American and Soviet space missions, as well as some studies conducted under simulated weightlessness, offers just a handful of objective studies on the physiology of sleep and circadian rhythms in space. Nevertheless, the data are remarkably consistent, and indicate that sleep can be of reasonably good quality in space. The risk of sleep loss and associated performance degradation appears to be a manageable one. However, one clear conclusion arises from this review: whatever the type of mission of flight plan, its success will depend on whether the principles of circadian and sleep-wake regulation have been taken into account during the planning phase of work-rest schedules. That is, satisfactory sleep and alertness is more likely to occur if crews maintain a reasonable (i.e., constant) relation with their normal terrestrial rhythm. This is not as easy a task as it may appear; indeed, unexpected, high-intensity operational demands have been the major cause of acute problems of sleep loss and performance degradation in space. Moreover, the growing complexity of space missions indicate that emergencies will never disappear. Therefore, one of the most important research challenges for future space missions is the development of strategies that could permit astronauts to function closest to maximal efficiency during intensive and prolonged work. Countermeasures for optimizing astronaut performance, as well as other factors affecting sleep and performance in space, are reviewed and discussed in detail in this paper.

Circadian Rhythm↗
PubMed1989

Kappa Delta Award paper. Tissue fluid pressures: from basic research tools to clinical applications.

The two basic research tools developed to measure tissue fluid pressure (wick catheter) and osmotic pressure (colloid osmometer) have undergone extensive validation and refinement over the past 20 years. Using these techniques, basic science investigations were undertaken of edema in Amazon reptiles, pressure-volume relations in animals and plants, adaptive physiology of Antarctic penguins and fishes, edema in spawning salmon, tissue fluid balance in humans under normal conditions and during simulated weightlessness, and orthostatic adaptation in a mammal with high and variable blood pressures--the giraffe. Following and sometimes paralleling this basic research have been several clinical applications related to use of our colloid osmometer and wick technique. Applications of the osmometer have included insights into (a) reduced osmotic pressure of sickle-cell hemoglobin with deoxygenation and (b) reduced swelling pressure of human nucleus pulposus with hydration or certain enzymes. Clinical uses of the wick technique have included (a) improvement of diagnosis and treatment of acute and chronic compartment syndromes, (b) elucidation of tissue pressure thresholds for neuromuscular dysfunction, and (c) development of a better tourniquet design for orthopaedics. This article demonstrates that basic research tools open up areas of basic, applied, and clinical research.

Animals↗
PubMed1994

Sympathetic nervous activity and cardiovascular variability after a 3-day tail suspension in rats.

The effects of a 3-day tail suspension on central and peripheral sympathetic activity were studied in rats by determining the in vivo noradrenaline (NA) turnover in the brain cell groups involved in central blood pressure control (A1, A2, A5 and A6) and in two peripheral organs, heart and kidneys. In addition, cardiovascular parameters and their variabilities were investigated by recording blood pressure (BP) and heart rate (HR) before and after suspension. These measurements were processed by spectrum analysis to assess the influence of tail suspension on autonomic balance. The NA turnover in the suspended rats was markedly reduced in A2 (-49%, P < 0.01) and A5 (-38%, P < 0.01) nuclei but unchanged in A1 and A6 cell groups compared with the control rats. Peripheral NA turnover was decreased in cardiac atria (-44%, P < 0.001) and ventricles (-27%, P < 0.01) while it was unchanged in kidneys after suspension. The BP, HR and their variabilities were similar in both groups of animals and showed no changes after suspension compared with baseline values. Spectrum analysis of BP and HR in our conscious suspended rats revealed no changes in power spectrum density or in peak frequencies. The discrepancy between the decrease in central sympathetic activity and the absence of changes in cardiovascular parameters after tail suspension raises the question of the validity of the tail suspended rat model when studying the cardiovascular deconditioning observed in humans after an exposure to actual or simulated weightlessness.

Animals↗