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At least 199 records · Page 11

Acute Hemodynamic Effects of the Braslet-M Device on the International Space Station

The Braslet-M occlusion device is prescribed for cosmonauts as a countermeasure for early phases of spaceflight to temporarily alleviate symptoms associated with the cephalad fluid shift. Using a multipurpose ultrasound (US) device onboard, we assessed the acute hemodynamic effects of the Bracelet-M device on a long duration International Space Station (ISS) crewmember. Methods A combination of just-in-time training and real-time remote expert assistance was used to conduct the imaging procedures. An HDI-5000 imager (Philips, Bothell, WA) was used, provided by the ISS Human Research Facility. Superficial femoral artery (SFA), femoral vein (FV) flow spectra were obtained at mid-thigh level. Left ventricle was imaged through the apical 4-chamber view, with Color M-Mode to measure propagation velocity (V (p)). After 10 minutes of Bracelet-M use, data collection was repeated. All data were transmitted in DICOM format to ground for analysis. Results With Braslet-M, cardiac V(p) slope decreased (56ms to 42ms). A stagnation signature in the FV was seen suggesting impeded flow (rouleaux formation, too-low-to-measure velocity, and increase in diameter). Quadri-phasic flow in SFA was seen both before and after Braslet-M application. Velocities in the SFA decreased with Braslet-M (65cm/sec to 52cm/sec) and so did the time velocity integrals (16.97 to 12.4); the flow pattern spoke of resistivity increase in the vascular bed. Conclusion In the long duration ISS crewmember we observed effects of lower extremity venous occlusion through both central and peripheral indicators. A part of circulating volume transferred to peripheral potential vascular space. Impediment to venous outflow was demonstrated objectively, with a commensurate change in the flow pattern of the main feeding artery. Central volume reduction caused lower V(p). Additional studies are warranted to determine the time course of the changes and the dynamics in interstitial fluid sequestration, as well as the safe levels and duration of the compression forces.

Hamilton, Douglas R.↗

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water-selective channel involved in interstitial fluid homeostasis, showed an upregulated trend in HS retinas; however, these results are preliminary. Total retinal thickness increased significantly (P = 0.049) in HS rats fed a resveratrol enriched diet compared to HS rats on a normal diet. This change appeared to be reversed during the 2 weeks of recovery post HS, but no differences in retina thickness were observed between HS animals and HS recovered animals when both groups consumed a normal diet. The reversibility of the increase in retinal thickness induced by resveratrol during HS may therefore reflect an interaction between the stress provoked by HS and the cytoprotective mechanisms elicited by resveratrol

Glass, Aziza↗

Expression of a Degradation-Resistant β-Catenin Mutant in Osteocytes Protects the Skeleton From Mechanodeprivation-Induced Bone Wasting

ABSTRACT Mechanical stimulation is a key regulator of bone mass, maintenance, and turnover. Wnt signaling is a key regulator of mechanotransduction in bone, but the role of β-catenin—an intracellular signaling node in the canonical Wnt pathway—in disuse mechanotransduction is not defined. Using the β-catenin exon 3 flox (constitutively active [CA]) mouse model, in conjunction with a tamoxifen-inducible, osteocyte-selective Cre driver, we evaluated the effects of degradation-resistant β-catenin on bone properties during disuse. We hypothesized that if β-catenin plays an important role in Wnt-mediated osteoprotection, then artificial stabilization of β-catenin in osteocytes would protect the limbs from disuse-induced bone wasting. Two disuse models were tested: tail suspension, which models fluid shift, and botulinum-toxin (botox)-induced muscle paralysis, which models loss of muscle force. Tail suspension was associated with a significant loss of tibial bone mass and density, reduced architectural properties, and decreased bone formation indices in uninduced (control) mice, as assessed by dual-energy X-ray absorptiometry (DXA), micro-computed tomography (µCT), and histomorphometry. Activation of the βcatCA allele in tail-suspended mice resulted in little to no change in those properties; ie, these mice were protected from bone loss. Similar protective effects were observed among botox-treated mice when the βcatCA was activated. RNAseq analysis of altered gene regulation in tail-suspended mice yielded 35 genes, including Wnt11, Gli1, Nell1, Gdf5, and Pgf, which were significantly differentially regulated between tail-suspended β-catenin stabilized mice and tail-suspended nonstabilized mice. Our findings indicate that selectively targeting/blocking of β-catenin degradation in bone cells could have therapeutic implications in mechanically induced bone disease. © 2019 American Society for Bone and Mineral Research.

59 BASIC BIOLOGICAL SCIENCES↗

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long–Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

Genetics & Heredity↗

Lower body negative pressure - The second manned Skylab mission

Results of orthostatic evaluations of the crew of Skylab 3 with lower body negative pressure (LBNP) stress tests during their 59-d mission are reported. Except for an inflight increase (rather than a decrease) in resting heart rates, results were essentially parallel to those observed in crewmen of the shorter Skylab 2 mission. Exaggerated elevations in heart rate and decreases in pulse pressure during LBNP stress inflight and immediately postflight corresponded to lowered orthostatic tolerance. Large decrements is resting calf size inflight and in total leg volume postflight indicated significant headward fluid shifts as had already been seen in the Skylab 2 crewmen. In addition, decreases in calf circumference gave no certain indication of a plateau over the 59 d inflight. Percentage volume increase in calf size during LBNP stress inflight was greater than those in either preflight or postflight tests.

Johnson, R. L.↗

Automated electroencephalography system and electroencephalographic correlates of space motion sickness, part 3

Computer quantification methods were used to analyze the Skylab electroencephalographic data obtained during the course of the M133 series of experiments. This undertaking was prompted by initial observations made during visual analysis of the tape-recorded sleep records where there appeared to be an increase of the alpha-rhythm frequency during some inflight recording sessions, as compared to preflight baseline observations. A number of potential etiological factors are identified and their various possible influences discussed. The presence of the zero-g state is thought to be an important factor, possibly influencing EEG through alteration of vestibular function and/or by producing fluid shifts secondary to loss of hydrostatic pressure.

Frost, J. D., Jr.↗

Skylab 4 crew observations

Comments on food, exercise, scheduling, medical training, the effect of fluid shift, and vestibular phenomena are briefly reported. A ballistocardiographic effect of around 60 beats per minute was observed several times for the whole Skylab cluster. Also experienced were light flashes that were well correlated with the South Atlantic anomaly.

E. G. Gibson↗

Physiological system integrations with emphasis on the respiratory-cardiovascular system

The integration of two types of physiological system simulations is presented. The long term model is a circulatory system model which simulates long term blood flow variations and compartmental fluid shifts. The short term models simulate transient phenomena of the respiratory, thermoregulatory, and pulsatile cardiovascular systems as they respond to stimuli such as LBNP, exercise, and environmental gaseous variations. An overview of the interfacing approach is described. Descriptions of the variable interface for long term to short term and between the three short term models are given.

Gallagher, R. R.↗

Development of an hypothesis for simulating anti-orthostatic bed rest

The Guyton model, modified by the addition of leg compartments and the effect of the gravity vector, was used to evaluate hypotheses describing leg dehydration and fluid shifts. While the study is not complete, the basic approach was shown to be useful by identifying important mechanisms, identifying systems which need further experimental description and by assisting in the development of a general hypothesis.

Leonard, J. I.↗

Study report on modification of the long term circulatory model for the simulation of bed rest

Modifications were made of the circulatory, fluid, and electrolyte control model which was based on the model of Guyton. The modifications included separate leg compartments and the addition of gravity dependency. It was found that these modifications allowed for more accurate bed rest simulation by simulating changes in the orthostatic gradient and simulating the response to the fluid shifts associated with bed rest.

Leonard, J. I.↗

Early cardiovascular adaptation to zero gravity simulated by head-down tilt

The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 deg, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 h. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin, and aldosterone inhibition.

Blomqvist, C. G.↗

Induced venous pooling and cardiorespiratory responses to exercise after bed rest

Venous pooling induced by a specially constructed garment is investigated as a possible means for reversing the reduction in maximal oxygen uptake regularly observed following bed rest. Experiments involved a 15-day period of bed rest during which four healthy male subjects, while remaining recumbent in bed, received daily 210-min venous pooling treatments from a reverse gradient garment supplying counterpressure to the torso. Results of exercise testing indicate that while maximal oxygen uptake endurance time and plasma volume were reduced and maximal heart rate increased after bed rest in the control group, those parameters remained essentially unchanged for the group undergoing venous pooling treatment. Results demonstrate the importance of fluid shifts and venous pooling within the cardiovascular system in addition to physical activity to the maintenance of cardiovascular conditioning.

Convertino, V. A.↗

Cardiovascular responses to weightlessness and ground-based simulations

Mission experience, from NASA and Soviet programs, on human cardiovascular responses to weightlessness, and the ability of bed rest studies to simulate these are discussed. In-flight effects include fluid shift to the upper body, decreased heart size, bone demineralization, orthostatic intolerance, and loss of exercise tolerance. All the cardiovascular changes that occur with weightlessness also occur with prolonged bed rest. They are most manifest when subjects stand suddenly, or undergo tilting or lower body negative pressure. The mechanisms which control these responses, e.g., the role of the central nervous system, are unclear.

Sandler, H.↗

The first dedicated life sciences mission - Spacelab 4

The details of the payload and the experiments in Spacelab 4, the first Spacelab mission dedicated entirely to the life sciences, are discussed. The payload of Spacelab 4, carried in the bay of the Shuttle Orbiter, consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. The payload contains complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. Animals used as experimental subjects will include squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The main scientific objectives of the investigations include the study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Other scientific objective include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs.

Cramer, D. R.↗

Sensitivity of bone cell populations to weightlessness and simulated weightlessness

A rat suspension model for simulating certain aspects of weightlessness is discussed. Perturbations in physiological systems induced by this head down suspension model are verified by flight data. Findings of a suppression of osteoblast differentiation help explain the inhibition of bone formation inflight and during Earth-bound simulations. Since the anatomical site for these studies was in the maxilla, which is gravity loaded but non weightbearing in ground-based simulations, the similarity of bone cell kinetic changes, both inflight and in the ground-based model, suggest that fluid shifts rather than unloading may play an important role in bone alterations, at least at this sampling site.

Roberts, W. E.↗

Cardiovascular responses to spaceflight

The cardiovascular system's adaptive changes during and after spaceflight are discussed. Cephalic fluid shifts are demonstrated by photographs along with calf girth and leg volume changes. Inflight measurements show an increase in average resting heart rate and systolic blood pressure, and a sympathetic-parasympathetic neural imbalance. Postflight findings include a small but reversible decrease in the left ventricular muscle mass. Since 1980, NASA's research has emphasized cardiovascular deconditioning and countermeasures: hemodynamic changes, endocrine and neurohumoral aspects, etiologic factors, and lower body negative pressure devices. Though human beings acclimate to the space environment, questions concerning the immediate and long-term aspects of spaceflight need to be answered for adequate planning of extended space missions.

Nicogossian, A.↗

Space motion sickness and vestibular adaptation to weightlessness

Theories of space motion sickness are discussed together with near future vestibular experiments for three Spacelab missions. The sensory conflict theory is covered, as well as theories involving unequal otolith masses, semicircular canals, cardiovascular adaptation and fluid shift toward the head, and extra-labyrinthine effects. Experiments will test the hypothesis that the sensitivity of the otolith organ response is shifted during weightlessness and that this shift carries over to the post-flight experience. Visual-vestibular-tactile interaction, vestibulo-ocular reflexes, ocular counterrolling, awareness of body position, otolith-spinal reflexes, and motion sickness susceptibility are among the parameters to be studied. Preflight and postflight tests will emphasize evaluation of any residual effects of the seven day weightless exposure on vestibulo-spinal and vestibulo-ocular pathways.

Young, L. R.↗

Simulating certain aspects of hypogravity - Effects on bone maturation in the nonweight bearing skeleton

For a determination of how the nonweight-bearing skeletons, i.e., lower jaws, of 41-day and 1-year old rats would respond to 10 or 14 days of partial skeletal unloading by elevating the hindquarters (PULEH), an experimental system to simulate the fluid shifts and unloading of portions of the skeleton which occur during spaceflight was developed. In comparison with the bone matrix mineralization recorded in the mandibles of rats flown in the Soviet 18.5 day Cosmos-1129 mission, the PULEH studies failed to produce spaceflight-like maturation defects.

Simmons, D. J.↗