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Exploring Endothelial Function Risk Factors and Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

Approximately 20% of astronauts on International Space Station missions experience ophthalmic pathologies including optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the cause of SANS is unknown, there are likely multiple contributing factors, including genetics, that may affect the response to spaceflight in affected individuals. B-vitamin status and the presence of specific one-carbon pathway single nucleotide polymorphism (SNP) alleles predicted the incidence of SANS pathologies in astronauts and in bed rest subjects. There are several hypotheses for how genetic variants could lead to SANS, specifically related to endothelial function. The biochemical pathway to which these genes are associated is intimately involved in maintaining endothelial function via nitric oxide synthase (eNOS) coupling and nitric oxide (NO) production. Furthermore, eNOS uncoupling can impair the functional status of the endothelial glycocalyx, which lines the entirety of the vascular lumen and affects endothelial function. Vascular distension, stasis and altered shear forces, which are associated with headward fluid shifts, may also contribute to glycocalyx dysfunction and shedding, resulting in endothelial dysfunction and increased vascular permeability and tissue edema, potentially contributing to optic nerve and optic disc edema in affected individuals. Given the findings relating genetics and the risk of optic disc edema in astronauts during flight and subjects during bed rest, further investigation is warranted. In this study, we will assess the same genetic variants in another bed rest study: AGBRESA. Some of the AGBRESA subjects developed optic disc edema, but their genetics have not been studied. Furthermore, we will test available urine samples from prior bed rest studies (VaPER and AGBRESA) for markers of glycocalyx degradation to expand our understanding of factors contributing to SANS.

S R Zwart↗
NASA NTRS1995

Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest

Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d) and with men consuming a normal diet during bed rest. At the end of the fast mean plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4-pyridoxic acid tended to be higher in the fasting subjects than in the low-vitamin B-6 group. The fasting subjects lost approximately 10% of their total vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6 group lost only approximately 4% of their vitamin B-6 pool. Compared with baseline, urinary excretion of pyridoxic acid was significantly increased during 17 wk of bed rest. There was no increase in pyridoxic acid excretion during a second 15-d bed rest study. These data suggest the possibility of complex interactions between diet and muscle metabolism that may influence indexes that are frequently used to assess vitamin B-6 status.

NASA Discipline Regulatory Physiology↗
NASA NTRS2010

International Standardization of Bed Rest Standard Measures

This slide presentation gives an overview of the standardization of bed rest measures. The International Countermeasures Working Group attempted to define and agree internationally on standard measurements for spaceflight based bed rest studies. The group identified the experts amongst several stakeholder agencys. It included information on exercise, muscle, neurological, psychological, bone and cardiovascular measures.

Cromwell, Ronita L.↗
NASA NTRS2017

Effects of Long Duration Spaceflight on Venous and Arterial Compliance: Bed Rest

The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Ribeiro, L. Christine↗
NASA NTRS2003

Sympathetic responses to Valsalva's manoeuvre following bed rest

The purpose of this study was to examine whether 14 days of head-down tilt bed rest (HDBR) alters autonomic regulation during Valsalva's manoeuvre (VM) and if this would predict blood pressure control during a 60 degrees head-up tilt (HUT) test. To examine autonomic control of blood pressure, we measured the changes in systolic (delta SBP) and diastolic (delta DBP) blood pressure between baseline and the early straining (Phase IIE) period of VM (20 sec straining to 40 mmHg; N = 7) in conjunction with changes in muscle sympathetic nerve activity (MSNA; microneurography) burst frequency (B/min) and total activity (% delta) from baseline over the 20-sec straining period. MSNA data were successfully recorded from 6 of the 7 individuals. The averaged responses from three repeated VMs performed in the supine position were compared between the pre- and post-HDBR tests. Compared with the pre-HDBR test, a greater reduction in SBP, DBP, and MAP was observed during Phase IIE following HDBR, p < 0.05. The increase in MSNA burst frequency during straining was augmented in the post- compared with the pre-HDBR test, p < 0.0001, as was the Phase IV blood pressure overshoot, p < 0.05. Although all subjects completed the 20-min pre-HDBR tilt test without evidence of hypotension or orthostatic intolerance, the post-HDBR test was stopped early in 5 of the 7 subjects due to systolic hypotension. The responses during the VM suggest that acute autonomic adjustments to rapid blood pressure changes are preserved after bed rest. Furthermore, MSNA and blood pressure responses during VM did not predict blood pressure control during orthostasis following HDBR.

NASA Discipline Musculoskeletal↗
NASA NTRS1998

Collagen cross-link excretion during space flight and bed rest

Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

NASA Center JSC↗
NASA NTRS2011

Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and elicits orthostatic issues present post-spaceflight (contributing to instability); however, it does not sufficiently address the vestibular dysfunction which occurs post-spaceflight.

Esteves, Julie↗
NASA NTRS1996

Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects

Endurance trained long distance runners and untrained individuals underwent three days of bed rest and oral glucose loading. Before and after bed rest, individuals were given glucose tolerance tests, and their heart rates, blood pressure, blood glucose levels, insulin levels, and catecholamine interactions were measured. Results indicated that glucose tolerance is more affected by bed rest-induced deconditioning in untrained individuals than in trained individuals.

NASA Discipline Regulatory Physiology↗
NASA NTRS1990

Bone mineral loss and recovery after 17 weeks of bed rest

The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88.

Non-NASA Center↗
NASA NTRS1994

Immune Response and Function: Exercise Conditioning Versus Bed-Rest and Spaceflight Deconditioning

Immune responses measured at rest immediately or some hours after exercise training (some with and some without increase in maximal oxygen uptake) gave variable and sometimes conflicting results; therefore, no general conclusions can be drawn. On the other hand, most immune responses were either unchanged (immunoglobulin, T cells, CD4+, and natural killer activity) or decreased (blood properdin, neutrophil phagocytic activity, salivary lysozymes, brain immunoglobulin A and G, and liver B lymphocytes and phytohemagglutinin activity) during prolonged bed rest. Some data suggested that exercise training during bed rest may partially ameliorate the decreased functioning of the immune system. Exercise and change in body position, especially during prolonged bed rest with plasma fluid shifts and diuresis, may induce a change in plasma protein concentration and content, which can influence drug metabolism as well as immune function. Leukocytosis, accompanied by lymphopenia and a depressed lymphocyte response, occurs in astronauts on return to Earth from spaceflight; recovery may depend on time of exposure to microgravity. It is clear that the effect of drugs and exercise used as countermeasures for microgravity deconditioning should be evaluated for their effect on an astronaut's immune system to assure optimal health and performance on long-duration space missions.

Greenleaf, J. E.↗
NASA NTRS1974

The metabolic and hemodynamic effects of prolonged bed rest in normal subjects

Investigation in six normal subjects of the effects of chronic bed rest on the interrelationships between cardiovascular hemodynamics, catecholamine metabolism, vascular reactivity, renin and aldosterone activity, and electrolyte and fluid balance. Negative sodium and potassium balances and reductions in plasma volume were observed in all subjects, but plasma renin activity and aldosterone secretory rate showed no significant change. Other findings included the observation that major decreases in sodium balance and plasma volume occurred in the early bed rest period and did not correlate closely with the degree of orthostatic intolerance.

Chobanian, A. V.↗
NASA NTRS2005

WISE-2005: Integrative Cardiovascular Responses with LBNP during 60-Day Bed Rest in Women

During 2005, 24 women will take part in the Women International Space-simulation for Exploration (WISE). In this paper we report on the first phase that studied 4 Exercise (EX+LBNP), 4 nutrition (NUT), and 4 no countermeasure control (CON) subjects. The EX+LBNP group completed regular exercise on a treadmill inside LBNP, flywheel resistive exercise and static periods of LBNP, and had recovery days. The NUT group received daily protein supplements. Integrative cardiovascular responses were obtained and here we report data for heart rate during LBNP, blood volume and angiotensin 11. LBNP was applied at 0, -10, -20 and -30 mmHg for 2-minutes for each stage. Blood was sampled prebed rest and on HDT-60. After 60-days head down bed rest, HR in the CON group increased by 6.1+/-2.8 bpm at rest and by 20.7+/-5.0 bpm at -30 mmHg LBNP. The EX+LBNP group had increases of 3.6+/-5.6 and 11.6+/-5.4 bpm, while the NUT group HR increased 2.6+/-3.1 and 9.4+/-3.6 bpm. The EX+LBNP group had almost no change in blood volume or plasma angiotensin II from pre-bed rest to HDT60, while both the CON and NUT groups had larger increases in plasma volume and almost double concentrations of angiotensin II. These data show a positive effect in the EX+LBNP group on the heart rate response as well as an unexpected possible benefit in the NUT group. Further studies are required to confirm possible cardiovascular benefits of the protein supplement.

Hughson, R. L.↗
NASA NTRS1984

VO2 kinetics of constant-load exercise following bed-rest-induced deconditioning

Previous studies have shown that the oxygen uptake kinetics during exercise and recovery may be changed by alterations in work intensity, prior exercise, muscle group involvement, ambient conditions, posture, disease state, and level of physical conditioning. However, the effects of detraining on oxygen uptake kinetics have not been determined. The present investigation has the objective to determine the effects of deconditioning following seven days of continuous head-down bed rest on changes in steady-state oxygen uptake, O2 deficit, and recovery oxygen uptake during the performance of constant-load exercise. The obtained results may provide support for previous proposals that submaximal oxygen uptake was significantly reduced following bed rest. The major finding was that bed-rest deconditioning resulted in a reduction of total O2 transport/utilization capacity during the transient phase of upright but not supine exercise.

Convertino, V. A.↗
NASA NTRS1993

Effect Of Leg Exercise On Vascular Volumes During Bed Rest

Report describes experiments on effects of no-exercise regimen and of two leg-exercise regimens on volumes of plasma, volumes of red blood cells, densities of bodies, and water balances of 19 men (32 to 42 years old) confined to minus 6 degrees-head-down bed rest for 30 days. Purpose of study to determine whether either or both exercise regimens maintain plasma volume and to relate levels of hypovolemia to body fluid balances. Results showed during bed rest, plasma volume maintained in isotomic group but not in other two groups, and no significant differences in body densities, body weights, or water balances among three groups. Concludes isotonic-exercise regimen better than isokinetic-exercise regimen for maintaining plasma volume during prolonged exposure to bed rest.

Greenleaf, J. E.↗
NASA NTRS1988

Effect of antiorthostatic bed rest on hepatic blood flow in man

Physiological changes that occur during exposure to weightlessness may induce alterations in blood flow to the liver. Estimation of hepatic blood flow (HBF) using ground-based weightlessness simulation models may provide insight into functional changes of the liver in crewmembers during flight. In the present study, HBF, indirectly estimated by indocyanine gree (ICG) clearance, is compared in 10 subjects during the normal ambulatory condition and antiorthostatic (-6 deg) bed rest. Plasma clearance of ICG was determined following intravenous administration of a 0.5-mg/kg dose of ICG to each subject on two separate occasions: once after being seated for 1 h, and once after 24 h of head-down bed rest. After 24 h of head-down bed rest, hepatic blood flow did not change significantly from the respective control value.

Putcha, L.↗
NASA NTRS1991

Effect of prolonged LBNP and saline ingestion on plasma volume and orthostatic responses during bed rest

Orthostatic intolerance remains a significant problem following space flight despite frequent use of the saline fluid-loading countermeasure and volitional use of an anti-gravity suite during reentry and landing. The purpose of this project is to examine the plasma volume (PV), endocrine, and orthostatic responses of bedrested subjects following 2-hr and 4-hr treatments of lower body negative pressure (LBNP) and saline ingestion. Ten healthy men were randomly assigned into 2 groups. Group A underwent a 4-hr LBNP/saline treatment on best rest day 5 and the 2-hr treatment on day 11. Group B underwent the 2-hr treatment on day 6 and the 4-hr treatment on day 10. Blood volume was determined before and after bed rest using radiolabelling. Changes in PV between measurements were calculated from changes in hematocrit and estimated red cell volume. Urinary excretion of anti-diuretic hormone (ADH) and aldosterone (ALD) were measured each day during the study. Orthostatic responses were measured using a ramp LBNP protocol before bed rest, before each treatment, and 24 hours after each treatment. Both 2-hr and 4-hr treatments resulted in a restoration of PV to pre-bed rest levels which persisted at least 24 hours. This increase in PV was associated with significant increases in urinary excretion of ADH and ALD. Twenty-four hours after the 4-hr treatment, the heart rate and pulse pressure response to LBNP were significantly lower and stroke volumes during LBNP were increased. Twenty-four hours after the 2-hr treatment, there was no evidence of improvement in orthostatic responses. These results suggest that a countermeasure which simply restores PV during space flight may not be sufficient for restoring orthostatic responses.

Fortney, Suzanne M.↗
NASA NTRS1982

Physiological responses to prolonged bed rest and fluid immersion in man: A compendium of research (1974 - 1980)

Water immersion and prolonged bed rest reproduce nearly all the physiological responses observed in astronauts in the weightless state. Related to actual weightlessness, given responses tend to occur sooner in immersion and later in bed rest. Much research was conducted on humans using these two techniques, especially by Russian scientists. Abstracts and annotations of reports that appeared in the literature from January 1974 through December 1980 are compiled and discussed.

Greenleaf, J. E.↗