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At least 289 records · Page 16

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NASA NTRS1997

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

NASA Discipline Cardiopulmonary↗

NASA NTRS1996

Cardiovascular effects of a fractional -Gz force during a relatively prolonged exposure

Artificial hypogravity was created by having subjects remain in a supine position while undergoing rotation in an artificial gravity simulator. Various cardiovascular variables, such as heart rate, cardiac output, thoracic electric impedance, and blood pressure were measured. Results indicated that the hypogravity force produced a headward fluid shift, as seen by a decrease in thoracic impedance, which triggers regulatory neuroendocrine mechanisms. These findings are presented and discussed.

Non-NASA Center↗

NASA NTRS1992

Cell culture for three-dimensional modeling in rotating-wall vessels: an application of simulated microgravity

High-density, three-dimensional cell cultures are difficult to grow in vitro. The rotating-wall vessel (RWV) described here has cultured BHK-21 cells to a density of 1.1 X 10(7) cells/ml. Cells on microcarriers were observed to grow with enhanced bridging in this batch culture system. The RWV is a horizontally rotated tissue culture vessel with silicon membrane oxygenation. This design results in a low-turbulence, low-shear cell culture environment with abundant oxygenation. The RWV has the potential to culture a wide variety of normal and neoplastic cells.

Weightlessness Simulation↗

NASA NTRS1994

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.

STS-56 Shuttle Project↗

NASA NTRS1988

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.

Non-NASA Center↗

NASA NTRS1996

Sampling of prenatal and postnatal offspring from individual rat dams enhances animal use without compromising development

To assess prenatal and postnatal developmental status in the offspring of a group of animals, it is typical to examine fetuses from some of the dams as well as infants born to the remaining dams. Statistical limitations often arise, particularly when the animals are rare or especially precious, because all offspring of the dam represent only a single statistical observation; littermates are not independent observations (biologically or statistically). We describe a study in which pregnant laboratory rats were laparotomized on day 7 of gestation (GD7) to ascertain the number and distribution of uterine implantation sites and were subjected to a simulated experience on a 10-day space shuttle flight. After the simulated landing on GD18, rats were unilaterally hysterectomized, thus providing a sample of fetuses from 10 independent uteruses, followed by successful vaginal delivery on GD22, yielding postnatal samples from 10 uteruses. A broad profile of maternal and offspring morphologic and physiologic measures indicated that these novel sampling procedures did not compromise maternal well-being and maintained normal offspring development and function. Measures included maternal organ weights and hormone concentrations, offspring body size, growth, organ weights, sexual differentiation, and catecholamine concentrations.

NASA Discipline Developmental Biology↗

NASA NTRS2002

The effect of microgravity and space flight on the chemical senses

The effect of space flight and microgravity on the chemical senses is reviewed. Skylab-4 and Soyuz 30-31 studies revealed changes in taste thresholds while no effect was found in a Canadian investigation (41-G) and conflicting results were obtained on another Soyuz mission. Two simulated microgravity studies found no effect on taste or smell sensitivity; while 5 other studies found an effect. Microgravity induces physiological changes including an upward shift of body fluids toward the head, which may lead to an attenuation of the olfactory component in the flavor of foods. Chemosensory changes may also relate to space sickness, Shuttle atmosphere, stress, radiation, and psychological factors.

Review, Academic↗

NASA NTRS1994

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.

NASA Discipline Number 18-10↗

NASA NTRS1999

Bone and hormonal changes induced by skeletal unloading in the mature male rat

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

NASA Discipline Musculoskeletal↗

NASA NTRS1994

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.

NASA Discipline Cell Biology↗

NASA NTRS1999

Microgravity cultivation of cells and tissues

In vitro studies of cells and tissues in microgravity, either simulated by cultivation conditions on earth or actual, during spaceflight, are expected to help identify mechanisms underlying gravity sensing and transduction in biological organisms. In this paper, we review rotating bioreactor studies of engineered skeletal and cardiovascular tissues carried out in unit gravity, a four month long cartilage tissue engineering study carried out aboard the Mir Space Station, and the ongoing laboratory development and testing of a system for cell and tissue cultivation aboard the International Space Station.

Review, Tutorial↗

NASA NTRS1988

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.

NASA Discipline Cardiopulmonary↗

NASA NTRS1998

Taxane recovery from cells of Taxus in micro- and hypergravity

Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol (TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2x10(-4)g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces.

Plants, Medicinal/chemistry/cytology↗

NASA NTRS1994

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.

NASA Program Space Physiology and Countermeasures↗

NASA NTRS1999

Gravisensing, apoptosis, and drug recovery in Taxus cell suspensions

Haploid and diploid cell suspensions of Taxus spp. were examined for their adaptive plasticity in response to simulated microgravity, unit gravity, and hypergravity. Cell suspensions produced the taxane, paclitaxel, (TAXOL (R)), which is useful for the treatment of various cancers. Amyloplasts contributed to taxane ring biosynthesis and to drug release at the cell wall. Drug-producing cells reacted as gravisensing osmotic tensiometers. In stressed cells, amyloplasts docked and fused in clusters to sites on the plasmalemma before taxane discharge into the culture medium. In simulated microgravity and compared to all other treatments, taxane production was reduced nearly 100-fold. The percent paclitaxel of total taxanes remained 3-to 6-fold greater, and biomass doubled. When p53-independent programmed cell death was induced, taxanes were released into the culture medium as free molecules (soluble and insoluble) or bound to membranes, nuclear fragments, xylan residues, and other particulate materials. Unit gravity and especially hypergravity promoted xylogenesis and significant drug overproduction. A model relating families of >touch = (TCH), taxane early response (TER), nuclear cycling, and apoptosis-regulating genes to gravisensing, cell wall modifications, and to taxane recovery accounted for most but not all of the observations.

Paclitaxel/biosynthesis↗

NASA NTRS1998

Intracranial pressure dynamics during simulated microgravity using a new noninvasive ultrasonic technique

It is believed that intracranial pressure (ICP) may be elevated in microgravity because a fluid shift toward the head occurs due to loss of gravitational blood pressures. Elevated ICP may contribute to space adaptation syndrome, because as widely observed in clinical settings, elevated ICP causes headache, nausea, and projectile vomiting, which are similar to symptoms of space adaptation syndrome. However, the hypothesis that ICP is altered in microgravity is difficult to test because of the invasiveness of currently-available techniques. We have developed a new ultrasonic technique, which allows us to record ICP waveforms noninvasively. The present study was designed to understand postural effects on ICP and assess the feasibility of our new device in future flight experiments.

NASA Center ARC↗

NASA NTRS2002

The exercise and environmental physiology of extravehicular activity

Extravehicular activity (EVA), i.e., exercise performed under unique environmental conditions, is indispensable for supporting daily living in weightlessness and for further space exploration. From 1965-1996 an average of 20 h x yr(-1) were spent performing EVA. International Space Station (ISS) assembly will require 135 h x yr(-1) of EVA, and 138 h x yr(-1) is planned for post-construction maintenance. The extravehicular mobility unit (EMU), used to protect astronauts during EVA, has a decreased pressure of 4.3 psi that could increase astronauts' risk of decompression sickness (DCS). Exercise in and repeated exposure to this hypobaria may increase the incidence of DCS, although weightlessness may attenuate this risk. Exercise thermoregulation within the EMU is poorly understood; the liquid cooling garment (LCG), worn next to the skin and designed to handle thermal stress, is manually controlled. Astronauts may become dehydrated (by up to 2.6% of body weight) during a 5-h EVA, further exacerbating the thermoregulatory challenge. The EVA is performed mainly with upper body muscles; but astronauts usually exercise at only 26-32% of their upper body maximal oxygen uptake (VO2max). For a given ground-based work task in air (as opposed to water), the submaximal VO2 is greater while VO2max and metabolic efficiency are lower during ground-based arm exercise as compared with leg exercise, and cardiovascular responses to exercise and training are also different for arms and legs. Preflight testing and training, whether conducted in air or water, must account for these differences if ground-based data are extrapolated for flight requirements. Astronauts experience deconditioning during microgravity resulting in a 10-20% loss in arm strength, a 20-30% loss in thigh strength, and decreased lower-body aerobic exercise capacity. Data from ground-based simulations of weightlessness such as bed rest induce a 6-8% decrease in upper-body strength, a 10-16% loss in thigh extensor strength, and a 15-20% decrease in lower-body aerobic exercise capacity. Changes in EVA support systems and training based on a greater understanding of the physiological aspects of exercise in the EVA environment will help to insure the health, safety, and efficiency of working astronauts.

Review↗

NASA NTRS2001

Simulated microgravity [bed rest] has little influence on taste, odor or trigeminal sensitivity

Anecdotal evidence suggests that astronauts' perceptions of foods in space flight may differ from their perceptions of the same foods on Earth. Fluid shifts toward the head experienced in space may alter the astronauts' sensitivity to odors and tastes, producing altered perceptions. Our objective was to determine whether head-down bed rest, which produces similar fluid shifts, would produce changes in sensitivity to taste, odor or trigeminal sensations. Six subjects were rested three times prior to bed rest, three times during bed rest and two times after bed rest to determine their threshold sensitivity to the odors isoamylbutyrate and menthone, the tastants sucrose, sodium chloride, citric acid, quinine and monosodium glutamate, and to capsaicin. Thresholds were measured using a modified staircase procedure. Self-reported congestion was also recorded at each test time. Thresholds for monosodium glutamate where slightly higher during bed rest. None of the other thresholds were altered by bed rest.

NASA Center JSC↗