Calcium movement of sarcoplasmic reticulum from hindlimb suspended muscle

The function of the sarcoplasmic reticulum (SR) was examined in the slow soleus and fast extensor digitorum longus (EDL) muscles of rats submitted to 14 days of weightlessness produced by hindlimb suspension (HS). Ca2+ uptake, Ca2+ release and passive Ca2+ leakage through the SR membrane were investigated using a method of caffeine-induced contracture on the single mechanically skinned fibers. In the SR of suspended soleus muscles, the rate of Ca2+ uptake was higher than in the control muscles. However, there was no difference between the suspended and control muscles in the rate of Ca2+ uptake of the SR in EDL after HS. In soleus muscles, Ca2+ movements of the SR from the suspended muscle acquired the properties that were similar to those of the control fast muscle. The study of Ca2+ leakage showed that the velocity and amount of passive Ca2+ leakage from SR in soleus and EDL were apparently increased after HS. The results suggested that the functional properties of the SR membrane in slow and fast muscles were changed after HS.     

Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension

The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.     

Artificial gravity: head movements during short-radius centrifugation.

Short-radius centrifugation is a potential countermeasure to long-term weightlessness. Unfortunately, head movements in a rotating environment induce serious discomfort, non-compensatory vestibulo-ocular reflexes, and subjective illusions of body tilt. In two experiments we investigated the effects of pitch and yaw head movements in participants placed supine on a rotating bed with their head at the center of rotation, feet at the rim. The vast majority of participants experienced motion sickness, inappropriate vertical nystagmus and illusory tilt and roll as predicted by a semicircular canal model. However, a small but significant number of the 28 participants experienced tilt in the predicted plane but in the opposite direction. Heart rate was elevated following one-second duration head turns. Significant adaptation occurred following a series of head turns in the light. Vertical nystagmus, motion sickness and illusory tilt all decreased with adaptation. Consequences for artificial gravity produced by short-radius centrifuges as a countermeasure are discussed. Grant numbers: NCC 9-58.     

Status of vestibular function after prolonged bedrest.

6 young, healthy, male volunteers were submitted to one week of head down (-4 degrees) bedrest. This position simulates the cerebral hemodynamic conditions in weightlessness. Measurements of vestibular equilibrium and of oculomotor system function were made before and after the prolonged bedrest. Analysis of the results indicates that vestibular responses, as measured by the maximal speed of the slow phase of the provoked nystagmus (caloric and sinusoidal rotatory stimulations), are decreased after prolonged bedrest. This statistically significant diminution requires confirmation with a greater number of cases. The reflex conflicting or interacting with the cervico-ocular and optokinetic reflexes on the one hand and the foveal vision on the other, is one of several possible explanations for the observed changes.     

Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.     

Prevention of muscle fibers atrophy during gravitational unloading: The effect of l-arginine administration

Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor l-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220–230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+l-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt l-arginine) and 14 days of hindlimb suspension+l-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group (p<0.05) and 40% and 25% in the HSN group, as compared to the CTR group (p<0.05), respectively. CSA of ST and FT muscle fibers were 25% and 16% larger in the HSL group in comparison with the HS group (p<0.05), respectively. The atrophy of FT muscle fibers in the HSL group was completely prevented since FT fiber CSA had no significant differences from the CTR group. In HS group, the percentage of fibers revealing either gaps/disruption of the dystrophin layer of the myofiber surface membrane increased by 27% and 17%, respectively, as compared to the controls (CTR group, p<0.05). The destructions in dystrophin layer integrity and reductions of desmin content were significantly prevented in HSL group. NO concentration decreased by 60% in the HS group (as well as HSN group) and at the same time no changes were detectable in the HSL group. This fact indicates the compensation of NO content in the unloaded muscle under l-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: l-arginine administration allows maintaining NO concentration in m.soleus at the level of cage control group, prevents from dystrophin layer destruction, decreases the atrogin mRNA concentration in the muscle and atrophy level under gravitational unloading.     

Effects of muscle electrostimulation during simulated weightlessness

In a 45-day experiment test subjects were exposed to bed rest with their heads down at -4 degrees C. Twice a day their muscles of the stomach, back, femur, and shin were stimulated with electric current for 25-30 min. The value of muscle tension was close to their maximum voluntary contraction. The main objective was to prevent muscle atrophy and to maintain their trophic and functional state. Physiological measurements were carried out together with morphological, cytochemical, and biometric evaluations. The tissue removed during biopsy from M. soleus 7 days before the test and on the 30th hypokinetic day was used as substrate. Electrostimulation affected favourably the tone and strength of muscles as well as their static and dynamic endurance. Morphological studies showed a positive effect of electrostimulation on the muscle tissue, preventing the development of atrophic processes. During the first post-hypokinetic day orthostatic tolerance increased.     

一种旋转失重模拟试验装置设计

为了验证某些航天产品在同时满足失重和自旋条件下的工作性能,设计了一种旋转失重模拟试验装置,由上下独立的单端承载旋转机构和转动平稳释放机构装配而成.文章给出装置的设计原理、转动应力参数仿真和平稳释放实现方法等,以及采用的关键技术.国内首例高速自旋失重试验的验证结果表明,旋转失重试验装置的使用克服了传统试验方法无法同时提供...     

Muscle atrophy associated with microgravity in rat: basic data for countermeasures

Morphological, contractile properties and myosin heavy chain (MHC) composition of rat soleus muscles were studied after 2 weeks of unloading (HS) and after 2 weeks of HS associated with selective deafferentation (HS + DEAF) at the level L4 and L5. The same significant reductions in muscle mass and tetanic tension were found after HS and HS + DEAF. However, the transformation of the slow-twitch soleus muscle towards a faster type characterized by a decrease in twitch time parameters and an increase in fast-twitch type MHC isoforms in HS did not appear in HS + DEAF conditions. Our results also showed that a pattern similar to firing rate of motoneurones innervating slow-twitch muscles inhibited the slow to fast fiber changes observed during HS. Nevertheless, neither the loss of mass or force output in the HS muscles were prevented by electrostimulation. Immobilization in a stretched position during HS maintained the muscle wet weight, mechanical and electrophoretical characteristics close to control values. We concluded that the decrease in mechanical strains imposed on the muscle during unloading was the main factor for the development of atrophy, while the kinetic changes might be predominantly modulated by the nervous command. These basic data suggested that some experimental conditions such as electrostimulation or stretching, could participate in countermeasure programmes.     

Decrease of contractile properties and transversal stiffness of single fibers in human soleus after 7-day “dry” immersion

The simulation model of “dry” immersion was used to evaluate the effects of plantar mechanical stimulation (PMS) and high frequency electromyostimulation (EMS) on the mechanical properties of human soleus fibers under the conditions of gravitational unloading. We examined contractile properties of single fibers by means of tensometry, transversal stiffness of sarcolemma and different areas of the contractile apparatus by means of atomic force microscopy. It was shown that there is a reduction of transversal stiffness in single muscle fibers under hypogravitational conditions. Application of different countermeasures could compensate this effect. Meanwhile pneumostimulation and electro stimulation act in quite different way. Therefore, pneumostimulation seems to be more effective. The data obtained can be considered as the evidence of the fact that such countermeasures as PMS and electromyostimulation influence on muscle fibers in quite different ways and PMS efficiency is likely to be higher. On the basis of our experimental data on transverse stiffness of mechanotransductional nodes and the contractile apparatus, we can assume that support stimulation allows prevention of destructive processes in muscle fibers. Electrostimulation seems to stimulate contractile activity only without suppression of impairment of the fiber mechanical properties.     

Static torsional otolith–cervical–ocular reflex after prolonged exposure to weightlessness and a 7-day immersion

To determine the role of the support-proprioceptive factor in the functioning of the vestibular system, in particular the static torsional otolith–cervical–ocular reflex (OCOR), comparative OCOR studies with videooculography recording were performed after a 7-day “dry” horizontal immersion (16 subjects) and after a prolonged (126–195 days) exposure to weightlessness (13 cosmonauts). For the first time, it was demonstrated that minimization of the support and proprioceptive afferentation may result in an inversion or absence of the static torsional OCOR and the development of a positional nystagmus with an inverted reflex. A comparative OCOR data analysis of cosmonauts and immersion subjects has revealed similarity of responses. However, changes in OCOR after immersion were noted in only 60% of the subjects, while after space flight, 90% of cosmonauts showed them. Post-flight changes were more frequent, marked and long-lasting. Statistical analysis has shown that there were significant differences between pre- and post-flight data according to both parametric and non-parametric methods of multiple comparisons, whereas only parametric methods have found significant differences within immersion data.     

Respective effects of hindlimb suspension, confinement and spaceflight on myotendinous junction ultrastructure

This study compares the effects of 14-day confinement and spaceflight with the respective effects of 8, 18 and 29-day hindlimb suspension on rat soleus and plantaris MTJ ultrastructure. Independently of the experimental situation, greater morphological changes were observed in the soleus as compared to the plantaris MTJ. 18 days of suspension and 14 days of confinement resulted in ultrastructural modifications of the digit-like processes in the soleus MTJ. Additional changes were observed in the myofibrils, microtendon and tendon after 29 days of suspension and 4 days of spaceflight. These results emphasize the influence of the intensity and duration of the muscle loading on the MTJ ultrastructure.     

Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.     

Does the centre of mass remain stable during complex human postural equilibrium tasks in weightlessness?

In normal gravity conditions the execution of voluntary movement involves the displacement of body segments as well as the maintenance of a stable reference value for equilibrium control. It has been suggested that centre of mass (CM) projection within the supporting base (BS) is the stabilised reference for voluntary action, and is conserved in weightlessness. The purpose of this study was to determine if the CM is stabilised during whole body reaching movements executed in weightlessness. The reaching task was conducted by two cosmonauts aboard the Russian orbital station MIR, during the Franco-Russian mission ALTAIR, 1993. Movements of reflective markers were recorded using a videocamera, successive images being reconstructed by computer every 40ms. The position of the CM, ankle joint torques and shank and thigh angles were computed for each subject pre- in- and post-flight using a 7-link mathematical model. Results showed that both cosmonauts adopted a backward leaning posture prior to reaching movements. Inflight, the CM was displaced throughout values in the horizontal axis three times those of pre-flight measures. In addition, ankle dorsi flexor torques inflight increased to values double those of pre- and post-flight tests. This study concluded that CM displacements do not remain stable during complex postural equilibrium tasks executed in weightlessness. Furthermore, in the absence of gravity, subjects changed their strategy for producing ankle torque during spaceflight from a forward to a backward leaning posture.     

Aquatic modules for bioregenerative life support systems based on the C.E.B.A.S. biotechnology [correction of biotechnilogy

Most concepts for bioregenerative life support systems are based on edible higher land plants which create some problems with growth and seed generation under space conditions. Animal protein production is mostly neglected because of the tremendous waste management problems with tetrapods under reduced weightlessness. Therefore, the "Closed Equilibrated Biological Aquatic System" (C.E.B.A.S.) was developed which represents an artificial aquatic ecosystem containing aquatic organisms which are adapted at all to "near weightlessness conditions" (fishes Xiphophorus helleri, water snails Biomphalaria glabrata, ammonia oxidizing bacteria and the rootless non-gravitropic edible water plant Ceratophyllum demersum). Basically the C.E.B.A.S. consists of 4 subsystems: a ZOOLOGICAL (correction of ZOOLOGICASL) COMPONENT (animal aquarium), a BOTANICAL COMPONENT (aquatic plant bioreactor), a MICROBIAL COMPONENT (bacteria filter) and an ELECTRONICAL COMPONENT (data acquisition and control unit). Superficially, the function principle appears simple: the plants convert light energy into chemical energy via photosynthesis thus producing biomass and oxygen. The animals and microorganisms use the oxygen for respiration and produce the carbon dioxide which is essential for plant photosynthesis. The ammonia ions excreted by the animals are converted by the bacteria to nitrite and then to nitrate ions which serve as a nitrogen source for the plants. Other essential ions derive from biological degradation of animal waste products and dead organic matter. The C.E.B.A.S. exists in 2 basic versions: the original C.E.B.A.S. with a volume of 150 liters and a self-sustaining standing time of more than 13 month and the so-called C.E.B.A.S. MINI MODULE with a volume of about 8.5 liters. In the latter there is no closed food loop by reasons of available space so that animal food has to be provided via an automated feeder. This device was flown already successfully on the STS-89 and STS-90 spaceshuttle missions and the working hypothesis was verified that aquatic organisms are nearly not affected at all by space conditions, i.e. that the plants exhibited biomass production rates identical to the sound controls and that as well the reproductive, and the immune system as the embryonic and ontogenic development of the animals remained undisturbed. Currently the C.E.B.A.S. MINI MODLULE is prepared for a third spaceshuttle flight (STS-107) in spring 2001. Based on the results of the space experiments a series of prototypes of aquatic food production modules for the implementation into BLSS were developed. This paper describes the scientific disposition of the STS-107 experiment and of open and closed aquaculture systems based on another aquatic plant species, the Lemnacean Wolffia arrhiza which is cultured as a vegetable in Southeastern Asia. This plant can be grown in suspension culture and several special bioreactors were developed for this purpose. W. arrhiza reproduces mainly vegetatively by buds but also sexually from time to time and is therefore especially suitable for genetic engineering, too. Therefore it was used, in addition, to optimize the C.E.B.A.S. MINI MODULE to allow experiments with a duration of 4 month in the International Space Station the basic principle of which will be explained. In the context of aquaculture systems for BLSS the continuous replacement of removed fish biomass is an essential demand. Although fish reproduction seems not to be affected in the shortterm space experiments with the C.E.B.A.S. MINI MODULE a functional and reliable hatchery for the production of siblings under reduced weightlessness is connected with some serious problems. Therefore an automated "reproduction module" for the herbivorous fish Tilapia rendalli was developed as a laboratory prototype. It is concluded that aquatic modules of different degrees of complexity can optimize the productivity of BLSS based on higher land plants and that they offer an unique opportunity for the production of animal protein in lunar or planetary bases.     

Effects of prolonged space flight on rat skeletal muscle

The effect of a 20-day space flight on water, Na+, K+, Mg2+, Ca2+ and glycogen contents as well as on activities of glycogen metabolism enzymes--glycogen synthetase and glycogen phosphorylase--of rat skeletal muscles was studied. This data is regarded as an integral test characterizing the state of contractile tissue of the animals at the final stage of flight aboard biosatellites. The measurements indicate that there were no significant changes of cations and glycogen contents nor of the enzymic activities in fast-twitch muscles during the 20-day spaceflight. At the same time dehydration in these muscles was observed, which disappeared on the 25th postflight day. In slow-twitch antigravitational skeletal muscle (m. soleus) there was a decrease of K+ and increase of Na+ in the tissue contents. The changes disappeared at the end of the on-earth readaptation period. From the pattern of these observations, we can conclude that the 20-day space flight leads to some reversible biochemical changes of the rat skeletal muscles. A conclusion can be drawn about necessity of creating, aboard the spaceship, an artificial load on antigravitational skeletal muscles.     

Artificial gravity--head movements during short-radius centrifugation: influence of cognitive effects

Short-radius centrifugation is a potential countermeasure against the effects of prolonged weightlessness. Head movements in a rotating environment, however, induce serious side effects: inappropriate vestibular ocular reflexes (VOR), body-tilt illusions and motion sickness induced by cross-coupled accelerations on a rotating platform. These are well predicted by a semicircular canal model. The present study investigates cognitive effects on the inappropriate VOR and the illusory sensations experienced by subjects rotating on a short-radius centrifuge (SRC). Subjects (N=19) were placed supine on a rotating horizontal bed with their head at the center of rotation. To investigate the extent to which they could control their sensations voluntarily, subjects were asked alternatively to "fight" (i.e. to try to resist and suppress) those sensations, or to "go" with (i.e. try to enhance or, at least, acquiesce in) them. The only significant effect on the VOR of this cognitive intervention was to diminish the time constant characterizing the decay of the nystagmus in subjects who had performed the "go" (rather than the "fight") trials. However, illusory sensations, as measured by reported subjective intensities, were significantly less intense during the "fight" than during the "go" trials. These measurements also verified an asymmetry in illusory sensation known from earlier experiments: the illusory sensations are greater when the head is rotated from right ear down (RED) to nose up (NU) posture than from NU to RED. The subjects habituated, modestly, to the rotation between their first and second sequences of trials, but showed no better (or worse) suppression of illusory sensations thereafter. No significant difference in habituation was observed between the "fight" and "go" trials.     

Motor coordination in weightless conditions revealed by long-term microgravity adaptation.

The functional approach to studying human motor systems attempts to give a better understanding of the processes behind planning movements and their coordinated performance by relying on weightlessness as a particularly enlightening experimental condition. Indeed, quantitative monitoring of sensorimotor adaptation of subjects exposed to weightlessness outlines the functional role of gravity in motor and postural organization. The recent accessibility of the MIR Space Station has allowed for the first time experimental quantitative kinematic analysis of long-term sensorimotor and postural adaptation to the weightless environment though opto-electronic techniques. In the frame of the EUROMIR'95 Mission, two protocols of voluntary posture perturbation (erect posture, EP; forward trunk bending, FTB) were carried out during four months of microgravity exposure. Results show that postural strategies for quasistatic body orientation in weightlessness are based on the alignment of geometrical body axes (head and trunk) along external references. A proper whole body positioning appears to be recovered only after months of microgravity exposure. By contrast, typically, terrestrial strategies of co-ordination between movement and posture are promptly restored and used when performing motor activities in the weightless environment. This result is explained under the assumption that there may be different sensorimotor integration processes for static and dynamic postural function and that the organisation of coordinated movement might rely stably on egocentric references and kinematics synergies for motor control.     

A review of the consequences of fluid and electrolyte shifts in weightlessness

This review describes the renal-endocrine mechanisms related to the early losses of fluid-electrolytes from the body during weightlessness as well as their contribution to longer term adaptation of fluid-electrolyte balance. The hypotheses presented were generated by a systematic analysis of body fluid and renal dynamics observed under conditions of actual and simulated spaceflight. These have increased our understanding of the effects of acute headward fluid shifts on renal excretion, the factors promoting excess sodium excretion and the regulation of extracellular fluid composition.     

Effect of weightlessness on sympathetic-adrenomedullary activity of rats.

Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)--as well as CA-degrading enzymes-monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.