Muscles in microgravity: from fibres to human motion

In simulated or actual microgravity, human and animal postural muscles undergo substantial atrophy: after about 270 days, the muscle mass attains a constant value of about 70% of the initial one. Most animal studies reported preferential atrophy of slow twitch fibres whose mechanical properties change towards the fast type. However, in humans, at the end of a 42-days bed rest study, a similar atrophy of slow and fast fibres was observed. After microgravity, the maximal force of several muscle groups showed a substantial decrease (6-25% of pre-flight values). The maximal power during very short "explosive" efforts of 0.25-0.30s showed an even greater fall, being reduced to 65% after 1 month and to 45% (of pre-flight values) after 6 months. The maximal power developed during 6-7s "all-out" bouts on an isokinetic cycloergometer was reduced to a lesser extent, attaining about 75% of pre-flight values, regardless of the flight duration. In these same subjects, the muscle mass of the lower limbs declined by only 9-13%. Thus, a substantial fraction of the observed decreases of maximal power is probably due to a deterioration of the motor co-ordination brought about by the absence of gravity. To prevent this substantial decay of maximal absolute power, we propose that explosive exercise be added to the daily in-flight training schedule. We also describe a system aimed at reducing cardiovascular deconditioning wherein gravity is simulated by the centrifugal acceleration generated by the motion of two counter rotating bicycles ridden by the astronauts on the inner wall of a cylindrical space module. Finally, cycling on circular or elliptical tracks may be useful to reduce cardiovascular deconditioning in permanently manned lunar bases. Indeed, on the curved parts of the path, a cyclist generates an outward acceleration vector (ac). To counterbalance ac, the cyclist must lean inwards, so that the vectorial sum of ac plus the lunar gravity tends to the acceleration of gravity prevailing on Earth.     

The problem of artificial gravity: The current state and prospects

The review deals with the use of artificial gravity in manned space flights. The need for studying this problem is substantiated, with special emphasis on its implications for future interplanetary flights. The deconditioning of astronauts and a loss of their tolerance to gravitational loads despite the use of various preventive procedures are briefly discussed. The efficiency of artificial gravity generated by a short-arm centrifuge (SAC) is evaluated; the possibility of the use of an SAC in space flights (the effect of the main parameters of G-load on humans, and its tolerability, efficiency, etc.) is considered. Both Russian and foreign data are presented on the use of SAC for simulating microgravity effects under ground-based conditions (immersion and ANOH) and in experiments on board biosatellites. It is emphasized that all the data (both original and the data in the literature) testify to the efficiency of SAC as a preventive and therapeutic facility alleviating the negative effects of simulated microgravity. The problems that have not been resolved to date are also presented.     

Acute exposure to microgravity does not influence the H-reflex with or without whole body vibration and does not cause vibration-specific changes in muscular activity

PurposeMany potential countermeasures for muscle and bone loss caused by exposure to microgravity require an uncompromised stretch reflex system. This is especially true for whole body vibration (WBV), as the main source of the neuromuscular activity during WBV has been attributed to stretch reflexes. A priori, it cannot be assumed that reflexes and Ia afferent transmission in particular have the same characteristics in microgravity as in normal gravity (NG). Therefore, the purpose of the study was to compare Ia afferent transmission in microgravity and NG and to assess how microgravity affects muscle activity during WBV.MethodsIn 14 participants, electromyographic activity of four leg muscles as well as Hoffmann-reflexes were recorded during NG and microgravity induced by parabolic flights.ResultsThe size of the Hoffmann-reflex was reduced during WBV, but did not differ during acute exposure to microgravity compared to NG. The influence of the gravity conditions on the electromyographic activity did not change depending on the vibration condition.ConclusionsAs far as the electromyographic activity of the recorded leg muscles is concerned, the effect of WBV is the same in microgravity as in NG. Moreover, Ia afferent transmission does not seem to be affected by acute exposure to microgravity when subjects are loaded with body weight and postural sway is minimized.     

Ground reaction forces during treadmill running in microgravity

Astronauts perform treadmill exercise during long-duration space missions to counter the harmful effects of microgravity exposure upon bone, muscle, and cardiopulmonary health. When exercising in microgravity, astronauts wear a harness and bungee system that provides forces that maintain attachment to the treadmill. Typical applied forces are less than body weight. The decreased gravity-replacement force could result in differences in ground-reaction force at a given running speed when compared to those achieved in normal gravity, which could influence the adaptive response to the performed exercise.     

Bone mineral and lean tissue loss after long duration space flight

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.     

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.     

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.     

Cytogenetic characteristic of osteogenic cells in vitro as perspective predictors of osteopenia under microgravity

Mechanical stimulation of bone tissue determined by earth gravity is one of the main factors mediating the nature, rate and direction of functional adaptation of the bone system in the process of onto- and phylogenesis. Theoretically expected losses of bone mass under condition of mechanical load deficit under microgravity (osteopenia, osteoporosis) may become a factor that limits the duration of space flights. As a result of long-term studies some properties and regularities of change in human tissue after prolonged space flights (for 5-7 months) were established.     

Applied horizontal force increases impact loading in reduced-gravity running

The chronic exposure of astronauts to microgravity results in structural degradation of their lower limb bones. Currently, no effective exercise countermeasure exists. On Earth, the impact loading that occurs with regular locomotion is associated with the maintenance of bone's structural integrity, but impact loads are rarely experienced in space. Accurately mimicking Earth-like impact loads in a reduced-gravity environment should help to reduce the degradation of bone caused by weightlessness. We previously showed that running with externally applied horizontal forces (AHF) in the anterior direction qualitatively simulates the high-impact loading associated with downhill running on Earth. We hypothesized that running with AHF at simulated reduced gravity would produce impact loads equal to or greater than values experienced during normal running at Earth gravity. With an AHF of 20% of gravity-specific body weight at all gravity levels, impact force peaks increased 74%, average impact loading rates increased 46%, and maximum impact loading rates increased 89% compared to running without any AHF. In contrast, AHF did not substantially affect active force peaks. Duty factor and stride frequency decreased modestly with AHF at all gravity levels. We found that running with an AHF in simulated reduced gravity produced impact loads equal to or greater than those experienced at Earth gravity. An appropriate AHF could easily augment existing partial gravity treadmill running exercise countermeasures used during spaceflight and help prevent musculoskeletal degradation.     

Characteristics of adaptation and maladaptation of human cardiovascular system under space flight conditions

The goal of this study was to analyze and generalize hemodynamic data collected over 20 years from 26 cosmonauts, who had flown from 8 to 438 days aboard orbital stations Salut-7 and Mir. This paper describes the results of ultrasonographic studies of the heart and arterial and venous peripheral vessels in different parts of human body as well as the study of venous capacity by occlusion aeroplethysmography. It was established that, at rest, the key hemodynamic parameters (the pumping function of the heart and blood supply of the brain) and integral parameters (blood pressure and heart rate) were best “protected” and remained stable throughout long exposure in microgravity. In the absence of gravitational stimulation, arterial resistance decreased in almost all vascular regions below the heart level; i.e., the antigravity distribution of the vascular tone was gradually lost as unneeded in microgravity. Venous hemodynamics was found to be most sensitive to microgravity: changes in it were expressed earlier and were more pronounced than in the arterial part of the vasculature. The changes included deceleration of venous return, a decrease in the vascular resistance in the lower body, and an increase in the leg’s venous network capacity. The functional test with the lower body’s negative pressure revealed a deterioration of gravity-dependent responses, which increased with an increase in the duration of the space flight. Cardiovascular deconditioning clearly manifested itself after the return to the Earth’s gravity as a decreased g-tolerance during reentry and orthostatic instability in the post-flight period. The results of this study confirmed the multifactorial genesis of orthostatic instability during space flights including blood redistribution, changes in the regulation of vascular tone of arterial and venous vessels in legs, and hypovolemia.     

Is HSP70 upregulation crucial for cellular proliferative response in simulated microgravity?

Astronauts are susceptible to a variety of conditions such as motion sickness, muscular atrophy, bone demineralization and cardiovascular deconditioning. These findings suggest that the adaptation to the absence of gravity is due, at least in part, to the effects exerted by microgravity at the cellular level. Indeed, a number of studies have indicated that gravity affects mammalian cell growth and differentiation through the modulation of gene expression. We have characterized the behaviour of endothelial cells and of the human monocytic cell line U937 cultured in the NASA-developed bioreactor to simulate microgravity, the Rotating Wall Vessels (RWV). In simulated microgravity endothelial cells showed a different behavior which was dependent from the species and from the district of origin, while U937 in the RWV proliferated slower than the controls. All the effects we observed were promptly reversible upon return to normal culture conditions. It is noteworthy that all the cells which maintained the capability to proliferate in microgravity upregulated the stress protein HSP70. We therefore propose that only the cells which sense microgravity as a stressful condition and, consequently, overexpress HSP70 maintain their proliferative potential in simulated microgravity.     

Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium

Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.     

Recording of blood pressure,heart rate and aortic nerve activity during parabolic flight in the rat via radio-telemetry

Exposure to microgravity induces cardiovascular deconditioning characterized by orthostatic hypotension when astronauts return to the earth. In order to understand the mechanism of cardiovascular deconditioning, it is necessary to clarify the changes in hemodynamics and the cardiovascular regulation system over the period of space flight. The telemetry system applied to freely moving animals will be a useful and appropriate technique for this kind of long term study of the cardiovascular system in the conscious animal during space flight. The purpose of the present study is twofold: firstly, to observe the detailed changes of arterial pressure and heart rate (HR) during microgravity elicited by the parabolic flight in order to study the acute effect of microgravity exposure on the cardiovascular system; and secondly, to test the feasibility of the telemetry system for recording blood pressure, HR and autonomic nervous activities continuously during space flight.     

Physiology in microgravity.

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.     

The current state of bone loss research: Data from spaceflight and microgravity simulators

Bone loss is a well documented phenomenon occurring in humans both in short‐ and in long‐term spaceflights. This phenomenon can be also reproduced on the ground in human and animals and also modeled in cell‐based analogs. Since space flights are infrequent and expensive to study the biomedical effects of microgravity on the human body, much of the known pathology of bone loss comes from experimental studies. The most commonly used in vitro simulators of microgravity are clinostats while in vivo simulators include the bed rest studies in humans and hindlimb unloading experiments in animals. Despite the numerous reports that have documented bone loss in wide ranges in multiple crew members, the pathology remains a key concern and development of effective countermeasures is still a major task. Thus far, the offered modalities have not shown much success in preventing or alleviating bone loss in astronauts and cosmonauts. The objective of this review is to capture the most recent research on bone loss from spaceflights, bed rest and hindlimb unloading, and in vitro studies utilizing cellular models in clinostats. Additionally, this review offers projections on where the research has to focus to ensure the most rapid development of effective countermeasures. J. Cell. Biochem. 114: 1001–1008, 2013. © 2012 Wiley Periodicals, Inc.     

Rotation in clinostat results in apoptosis of osteoblastic ROS 17/2.8 cells

Clinostat is an effective, ground-based tool which can be used to verify data from space flight, and to test hypotheses and experimental conditions for eventual space flights. Rotation in clinostat appears to mimic the microgravity environment by nulling the gravitational vector by continuous averaging. In the present study, we exposed osteoblast-like ROS 17/2.8 cells to a vector-averaged gravity environment in a clinostat and found that the cells undergo apoptotic death during the first 24 hr of clino-rotation. We suggest that apoptosis might be one of the mechanisms for reduced bone formation as observed in actual space flights.     

Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity.

Bed rest and spaceflight reduce exercise fitness. Supine lower body negative pressure (LBNP) treadmill exercise provides integrated cardiovascular and musculoskeletal stimulation similar to that imposed by upright exercise in Earth gravity. We hypothesized that 40 min of supine exercise per day in a LBNP chamber at 1.0-1.2 body wt (58 +/- 2 mmHg LBNP) maintains aerobic fitness and sprint speed during 15 days of 6 degrees head-down bed rest (simulated microgravity). Seven male subjects underwent two such bed-rest studies in random order: one as a control study (no exercise) and one with daily supine LBNP treadmill exercise. After controlled bed-rest, time to exhaustion during an upright treadmill exercise test decreased 10%, peak oxygen consumption during the test decreased 14%, and sprint speed decreased 16% (all P < 0.05). Supine LBNP exercise during bed rest maintained all the above variables at pre-bed-rest levels. Our findings support further evaluation of LBNP exercise as a countermeasure against long-term microgravity-induced deconditioning.     

The mouse as a model of cardiovascular adaptations to microgravity.

There are a multitude of physiological adaptations to microgravity, involving the cardiovascular, neuromuscular, and neuroendocrine systems. Some of these adaptations lead to cardiovascular deconditioning on return to normal gravity, posing a threat to human functional integrity after long-term spaceflight. Animal models of microgravity, e.g., tail suspension in rats, have yielded important information regarding the mechanism of these adaptations and have been useful in the design of countermeasures. The mouse could potentially be a useful experimental model, given its small size (smaller and lighter payload) and the powerful tools of experimental mouse genetics, which allow us to dissect mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide range of cardiovascular responses to simulated microgravity, including alterations in heart rate, exercise capacity, peripheral arterial vasodilatory responsiveness, and baroreflex response. These responses are qualitatively similar to many of those demonstrated in humans during spaceflight and in rats using tail suspension, although there are some important differences. Thus the mouse has value as a model for studies of cardiovascular changes during microgravity; however, investigators must maintain an appreciation of important species differences.     

"Critical periods" in vestibular development or adaptation of gravity sensory systems to altered gravitational conditions?

1. A feature of sensory, neuronal and motor systems is the existence of a critical period during their development. Modification of environmental conditions during this specific period of life affects development in a long-term manner, or even irreversibly. Deprivation is the prefered approach to study the existence and duration of critical periods. For gravity sensory systems, space flights offer the only opportunity for deprivation conditions. 2. Studies in a fish (Oreochromis mossambicus) and an amphibian (Xenopus laevis) revealed a significant sensitivity of their roll-induced static vestibuloocular reflex (rVOR) to a 9- to 10-day gravity deprivation (microgravity) during a spaceflight. In some instances, the rVOR was augmented after the flight as demonstrated in young Oreochromis which were launched when their rVOR had not been developed, and in Xenopus tadpoles launched after their rVOR had developed. Fish which could perform the rVOR at launch were insensitive to microgravity exposure. A similar insensitivity to microgravity was observed in Xenopus tadpoles with normal body shape which had not yet developed their rVOR at launch. Some tadpoles, however, developed an upward bended tail during their space flight; their rVOR was significantly depressed after termination of microgravity independent of the age at onset of the flight. Hypergravity depressed the rVOR for all so far tested developmental stages in both Oreochromis and Xenopus. 3. Both adaptive processes during exposure to altered gravity as well as the existence of a critical period in vestibular development might be responsible for the modulation of the rVOR recorded after exposure to altered gravity. Deprivation studies have to be extended to older developmental stages to test the possibility of a critical period; however, this approach is limited due to the low number of space flights.