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PubMed1988

Biomedical support of man in space.

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.

Adaptation, Physiological↗
PubMed2006

Proteomic analysis of mice hippocampus in simulated microgravity environment.

Space travel induces many deleterious effects on the flight crew due to the '0' g environment. The brain experiences a tremendous fluid shift, which is responsible for many of the detrimental changes in physical behavior seen in astronauts. It therefore indicates that the brain may undergo major changes in its protein levels in a '0' g environment to counteract the stress. Analysis of these global changes in proteins may explain to better understand the functioning of brain in a '0' g condition. Toward such an effort, we have screened proteins in the hippocampus of mice kept in simulated microgravity environment for 7 days and have observed a few changes in major proteins as compared to control mice. Essentially, the results show a major loss of proteins in the hippocampus of mice subjected to simulated microgravity. These changes occur in structural proteins such as tubulin, coupled with the loss of proteins involved in metabolism. This preliminary investigation leads to an understanding of the alteration of proteins in the hippocampus in response to the microgravity environment.

Animals↗
PubMed1999

Detection of apoptosis in chloroplasts and nuclei in different gravitational environments.

Plant cells either die by "accident" (traumatic cell death) or by "design" (programmed cell death; PCD). There is clear evidence that cell death during plant development and interactions with the environment involves PCD (in Gray and Johal, 1998). K. daigremontiana reproduces asexually by forming plantlets from leaf indentations which fall to soil and convert into adult plants. In nature, its entire plant body except leaf-plantlets senesces as consequence of floral differentiation or stressful environmental conditions. At unit gravity, PCD precedes plantlet detachment from the mother-leaf, leading to an abscission scar after plantlet fall. Earlier experiments have shown that leaf-plantlet formation and asexual reproduction increased with short duration hypergravity treatments and decreased in simulated hypergravity (Pedroso and Durzan, 1998). The present experiments were designed to determine if and what type of cell death occurs following gravitational changes, and the sequence of events leading to it. Our study shows that changes in gravitational environment cause a burst in nitric oxide, followed by a sequence of events that may ultimately led to programmed cell death by apoptosis.

Apoptosis↗
PubMed2000

Histological examination on edema formation in the rabbit brain exposed to head-down tilt.

Previous studies demonstrated that exposure to simulated microgravity, head-down tilt (HDT), caused cephalad fluid shift, increased capillary pressure in the head, and produced facial edema and nasal congestion. It is also known that exposure to HDT affects hemodynamics in the brain. Cerebral blood flow (CBF) velocity increases for at least 6 hours after the onset of 6 degrees HDT in humans. Intracranial pressure (ICP) elevates during 6 degrees HDT in humans and monkeys. However, there is little information regarding edema formation in the brain due to HDT except a morphological study reported by Kaplansky and colleagues who showed that perivascular edema occurred in the monkey brain after 7 days of 6 degrees HDT. Thus, it is interesting to examine whether edema formation occurs in the other animal model for simulation of microgravity, since several factors such as the duration of HDT, angle of HDT, and species difference may affect the result. In the present study, formation of brain edema was investigated by histological examinations in rabbits exposed to 45 degrees HDT for 2 days or 8 days. We hypothesized that HDT causes brain edema which can be demonstrated as extravasation of plasma constituents and histological changes.

Animals↗
PubMed1998

Microgravity simulations with human lymphocytes in the free fall machine and in the random positioning machine.

The purpose of this paper is to present the results obtained in our laboratory with both instruments, the FFM [free fall machine] and the RPM [random positioning machine], to compare them with the data from earlier experiments with human lymphocytes conducted in the FRC [fast rotating clinostat] and in space. Furthermore, the suitability of the FFM and RPM for research in gravitational cell biology is discussed.

Cells, Cultured↗
PubMed1997

Time course and reversibility of arterial vasoreactivity changes in simulated microgravity rats.

Recent works have shown that postflight orthostatic intolerance involves multiple alterations in physiological function during actual or simulated microgravity. In our previous work, we demonstrated that 14-day tail-suspension resulted in an impaired ability of vascular smooth muscle to develop tension in arteries confined to the hindquarter, which have been suggested as an important factor accounting for the occurrence of orthostatic intolerance. To our knowledge, data on arterial vasoreactivity alterations induced by simulated microgravity longer than two weeks are not found. The aim of the present work was to characterize the time course of alterations in vasoconstrictor properties of hindquarter arteries during tail-suspension up to eight weeks, and to examine whether these alterations are reversible.

Adaptation, Physiological↗
PubMed2001

Bed-rest studies for the International Space Station.

The microgravity experienced during space flight induces physiological changes that affect astronauts' health and performance. Simulations such as prolonged bed rest can mimic some of these changes and provide study conditions that are more accessible than during space flight itself. Previous studies, including several long and short-term bed-rest campaigns supported by ESA, have yielded significant medical data on the physiological changes induced by space flight. These data are being used extensively to study the effects of various countermeasures on those physiological changes.

Bed Rest↗
PubMed2003

Parathyroid hormone-related protein is a gravisensor in lung and bone cell biology.

Parathyroid Hormone-related Protein (PTHrP) has been shown to be essential for the development and homeostatic regulation of lung and bone. Since both lung and bone structure and function are affected by microgravity, we hypothesized that 0 x g down-regulates PTHrP signaling. To test this hypothesis, we suspended lung and bone cells in the simulated microgravity environment of a Rotating Wall Vessel Bioreactor, which simulates microgravity, for up to 72 hours. During the first 8 hours of exposure to simulated 0 x g, PTHrP expression fell precipitously, decreasing by 80-90%; during the subsequent 64 hours, PTHrP expression remained at this newly established level of expression. PTHrP production decreased from 12 pg/ml/hour to 1 pg/ml/hour in culture medium from microgravity-exposed cells. The cells were then recultured at unit gravity for 24 hours, and PTHrP expression and production returned to normal levels. Based on these findings, we have obtained bones from rats flown in space for 2 weeks (Mission STS-58, SL-2). Analysis of PTHrP expression by femurs and tibias from these animals (n=5) revealed that PTHrP expression was 60% lower than in bones from control ground-based rats. Interestingly, there were no differences in PTHrP expression by parietal bone from space-exposed versus ground-based animals, indicating that the effect of weightlessness on PTHrP expression is due to the unweighting of weight-bearing bones. This finding is consistent with other studies of microgravity-induced osteoporosis. The loss of the PTHrP signaling mechanism may be corrected using chemical agents that up-regulate this pathway. In conclusion, PTHrP represents a stretch-sensitive paracrine signaling mechanism that may sense gravity.

Adaptation, Physiological↗
PubMed1989

Plant cell in the process of the adaptation to simulated microgravity.

Analysis of structural-and-functional rearrangements in the organelles of meristematic, differentiating and differentiated cells of pea root under microgravity demonstrated certain consistencies in their manifestation, namely: a) heterogeneity of the organelles in a cell population with respect to the degree of the rearrangements; b) coincidence of a spatial succession in development; c) increased reactivity under changes in functional load during cell growth and differentiation; d) enhanced activity when a cell loses its specific functions (replacement of functions). It is assumed that microgravity does not prevent the development of certain adaptative reactions of organisms at the cellular level.

Adaptation, Physiological↗
PubMed1994

Vector-averaged gravity does not alter acetylcholine receptor single channel properties.

To examine the physiological sensitivity of membrane receptors to altered gravity, we examined the single channel properties of the acetylcholine receptor (AChR), in co-cultures of Xenopus myocytes and neurons, to vector-averaged gravity in the clinostat. This experimental paradigm produces an environment in which, from the cell's perspective, the gravitational vector is "nulled" by continuous averaging. In that respect, the clinostat simulates one aspect of space microgravity where the gravity force is greatly reduced. After clinorotation, the AChR channel mean open-time and conductance were statistically not different from control values but showed a rotation-dependent trend that suggests a process of cellular adaptation to clinorotation. These findings therefore suggest that the ACHR channel function may not be affected in the microgravity of space despite changes in the receptor's cellular organization.

Acetylcholine↗
PubMed1994

Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight.

We carried out parallel experiments first on the slow clinostat and then in space-flight to examine the effects of altered gravity on the aggregation of the nicotinic acetylcholine receptors and the structure of the cytoskeleton in cultured Xenopus embryonic muscle cells. By examining the concordance between results from space flight and the clinostat, we tested whether the slow clinostat is a relevant simulation paradigm. Space-flown cells showed marked changes in the distribution and organization of actin filaments and had a reduced incidence of acetylcholine receptor aggregates at the site of contact with polystyrene beads. Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly altered.

Acetylcholine↗
PubMed1988

Problems in analysis of data from muscles of rats flown in space.

Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

Adaptation, Physiological↗
PubMed2003

[The problem of creation of artificial gravity with the use of a short-radius centrifuge for medical support of interplanetary piloted missions].

On the evidence of orbital flights, the system of countermeasures against the effects of microgravity does not fully make for deconditioning of a number of human organs and systems and recovery of preflight physical status and working ability of members of long-term missions takes 1.5 to 2 mos. of the post-flight rehabilitation. In order to maintain the physical form, health and performance of crews in future interplanetary missions, we should be ready to offer them a novel countermeasure, i.e. regular sessions of artificial gravity generated by a short-radius centrifuge (SRC) on board vehicles. The articles presents the substantiation and concept of ground-based simulation studies of health benefits from SRC in interplanetary missions. Of primary concern is development of SRC regimens that will put up a strong opposition to microgravity, assure crew safety, and reduce to the minimum time to fulfill the in-flight countermeasure program. Answers to arising questions can be found by consolidation of the expertise and resources of the countries willing to meet this challenge.

Adaptation, Physiological↗
PubMed1998

Zinc distribution in various tissues, (brain, eye, skin, muscle and blood) of rat during hindlimb suspension.

Postural changes in 1-G environment induce well documented haemodynamic changes. On going from Earth's 1-G environment to the microgravity of space a marked cephalic blood volume shift occurs in humans with a subsequent loss of 2-3 L of fluid determined by diuresis and decreased fluid intake. Moreover, a number of transient changes in serum concentrations of sodium, potassium and calium have been observed in astronauts during spaceflight. It is conceivable that changes in the fluid status, and reduced muscle activities, which are changed by the microgravity environment, would also result in redistribution of some trace elements, such as zinc, copper and manganese. In particular, zinc metabolism, directly involved in many physiological processes, can be altered by a wide variety of factors including stress, rest, exercise, hormones and diet. Some of the microgravity-induced responses in space can be simulated in humans by using the posture of head-down tilt, and in rat by using the posture of hindlimb suspension. The aim of the present study was to investigate the effects of hindlimb suspension for 3-14 days on sodium, potassium and zinc content in various rat tissues including blood, muscle, brain, eye and nose's skin.

Animals↗
PubMed1994

Hormonal and metabolic responses of hypophysectomized rats with head-down suspension.

The primary purpose of this investigation was to secure select anatomical and physiological measurements from hypophysectomized rats and their sham-operated control to determine how various endocrine influences could be modified by conditions of simulated microgravity. The focal point of the study was the exercise responses after head-down suspension; however, we were also interested in obtaining insights on nonexercise-related mechanisms. Since more details and information concerning this study will be published elsewhere, we will highlight those findings which warrant further research.

Animals↗
PubMed1995

Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat.

Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days head-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.

Animals↗
PubMedDate not supplied

Cell-to-cell interactions in changed gravity: ground-based and flight experiments.

Cell-to-cell interactions play an important role in all physiological processes and are mediated by humoral and mechanical factors. Mechanosensitive cells (e.g., osteocytes, chondrocytes, and fibroblasts) can be studied ex vivo to understand the effects of an altered gravity environment. In particular, cultured endothelial cells (EC) are very sensitive to a broad spectrum of mechanical and biochemical stimuli. Earlier, we demonstrated that clinorotation leads to cytoskeletal remodeling in cultured ECs. Long-term gravity vector changes also modulate the expression of surface adhesion molecules (ICAM-1, E-selectin, VCAM-1) on cultured ECs. To study the interactions of geterological cells, we cocultured endothelial monolayers and human lymphocytes, immune cells and myeloleucemic (K-560) cells. It was found that, although clinorotation did not alter the basal adhesion level of non-activated immune cells on endothelial monolayers, the adhesion of PMA-activated lymphocytes was increased. During flight experiments onboard the Russian segment of the International Space Station, we measured the cytotoxic activity of natural killer (NK) cells incubated with labeled target cells. It was found that immune cells in microgravity retained their ability to contact, recognize, and destroy oncogenic cells in vitro. Together, our data concerning the effects of simulated and real microgravity suggest that, despite changes in the cytoskeleton, cell motility, and expression of adhesion molecules, cell-cell interactions are not compromised, thus preserving the critical physiological functions of immune and endothelial cells.

Cell Adhesion↗
PubMed1999

Influence of simulated microgravity on cardiovascular and hemodynamic parameters in Dahl salt-sensitive rats.

Prolonged exposure to microgravity, in humans, induces cardiovascular deconditioning and impairment of baroreflex activity partially as a result of fluid and electrolyte shifts. Animal models of simulated microgravity have been developed to mimic the above responses. We examined the effects of both 24 hr whole body suspension and 7 day tail-suspension and the subsequent 6 hr post-suspension in salt-loaded (2 wks on 8% NaCl diet) Dahl salt-sensitive rats. In both models, mean arterial pressure (MAP) and heart rate (HR) were unchanged during the suspension period. Upon release from suspension, there was no difference in the MAP or HR responses. Blood flows measured in the lower abdominal aorta and renal artery were not different between suspended and control animals. In both models, there was a similar body weight reduction in all groups. MAP responses to both phenylephrine (PHE) and sodium nitroprusside (SNP) were not affected by simulated microgravity. The HR response to SNP in suspended animals was greater than that of control animals; whereas, PHE-induced responses were not different. These data support the notion that simulated microgravity did not alter the MAP responses to SNP and PHE, however, HR responses were enhanced by SNP in the salt-loaded Dahl rats. In addition, salt-sensitivity/salt-loading prevents the reduction in MAP observed post-suspension in normotensive rats.

Animals↗