Head-down Bed Rest Research Articles

Four-day Head-down Tilt Bed Rest as a Model for Studying Rapid Alterations in Hemoglobin Mass

Rapid decreases in hemoglobin mass (Hbmass) have been reported in healthy humans with spaceflight and following descent from high altitude. It has been proposed that a selective increase in the destruction of young red blood cells (RBCs) mediates these decreases but conclusive evidence demonstrating neocytolysis is lacking. Based on the proposed triggers and time course of adaptation during spaceflight, we hypothesized that 4 days of −6° head-down tilt bed rest (HDTBR) would cause a rapid decrease in Hbmass that would be associated with evidence of increased RBC destruction. PURPOSE: To examine changes in Hbmass before (PRE), 5 hours after (POST), and 5 days after (POST5) 4 days of HDTBR. METHODS: Seven healthy, recreationally active men (age: 21 ± 3 years, peak oxygen uptake: 50 ± 6 mL kg-1 min-1) completed 4 days of HDTBR. Hbmass was assessed using the optimized carbon monoxide rebreathing method. Markers of RBC production and destruction assessed included [erythropoietin] ([EPO]), [soluble transferrin receptor] ([sTfr]), reticulocyte count, [ferritin], [haptoglobin], and [bilirubin]. RESULTS: [EPO] decreased by 30 ± 33% from PRE to POST (p = 0.028). Contrary to our hypothesis, Hbmass was increased by 4.0 ± 4.3% from PRE to POST (p = 0.014) before decreasing to a level 3.6 ± 2.4% below PRE at POST5 (p = 0.027). From PRE to POST, [haptoglobin] increased 66 ± 73% (p = 0.013), [bilirubin] decreased 26 ± 34% (p = 0.054), [ferritin] increased 17 ± 17 % (p = 0.012), and reticulocyte count remained stable. From PRE to POST5, sTfr decreased 17 ± 5% (p = 0.018) but there were no significant alterations in [ferritin], [haptoglobin], [bilirubin] or reticulocyte count. CONCLUSION: Our findings suggest that 4-day HDTBR results in a transient increase in Hbmass that may be influenced by decreased RBC destruction. However, since the POST measurement occurred following re-ambulation, a potential role for other factors (i.e., spleen contraction) on the increase in Hbmass cannot be excluded. The decrease in Hbmass at POST5 appears to be mediated by decreased RBC production rather than increased RBC destruction. These findings highlight the need to re-examine the time course and mechanisms of Hbmass alterations with short-term spaceflight and simulated microgravity.

Haemoglobin mass alterations in healthy humans following four-day head-down tilt bed rest.

What is the central question of this study? Is haemoglobin mass (Hbmass) decreased following 4days of head-down tilt bed rest (HDTBR), and does increased red blood cell (RBC) destruction mediate this adaptation? What is the main finding and its importance? Haemoglobin mass was increased immediately following HDTBR, before decreasing below baseline 5days after return to normal living conditions. The transient increase in Hbmass might be the result of decreased RBC destruction, but it is also possible that spleen contraction after HDTBR contributed to this adaptation. Our data suggest that the decreased Hbmass 5days following HDTBR resulted from decreased RBC production, not increased RBC destruction. Rapid decreases in haemoglobin mass (Hbmass) have been reported in healthy humans following spaceflight and descent from high altitude. It has been proposed that a selective increase in the destruction of young red blood cells (RBCs) mediates these decreases, but conclusive evidence demonstrating neocytolysis in humans is lacking. Based on the proposed triggers and time course of adaptation during spaceflight, we hypothesized that Hbmass would be reduced after 4 days of -6deg head-down tilt bed rest (HDTBR) and that this would be associated with evidence for increased RBC destruction. We assessed Hbmass in seven healthy, recreationally active men before (PRE), 5h after (POST) and 5 days after (POST5) 4days of HDTBR. The concentration of erythropoietin decreased from 7.1±1.8 mIU ml(-1) at PRE to 5.2±2.8 mIU ml(-1) at POST (mean±SD; P=0.028). Contrary to our hypothesis, Hbmass was increased from 817±135g at PRE to 849±141g at POST (P=0.014) before decreasing below PRE to 789±139g at POST5 (P=0.027). From PRE to POST, the concentration of haptoglobin increased from 0.54±0.32 to 0.68±0.28gl(-1) (P=0.013) and the concentration of bilirubin decreased from 0.50±0.24 to 0.32±0.11mg dl(-1) (P=0.054), suggesting that decreased RBC destruction might have contributed to the increased Hbmass. However, it is possible that spleen contraction following HDTBR also played a role in the increase in Hbmass at POST, but as the transient increase in Hbmass was unexpected, we did not collect data that would provide direct evidence for or against spleen contraction. From PRE to POST5, the concentration of soluble transferrin receptor decreased from 20.7±3.9 to 17.1±3.3nmoll(-1) (P=0.018) but the concentrations of ferritin, haptoglobin and bilirubin were not significantly altered, suggesting that the decrease in Hbmass was mediated by decreased RBC production rather than increased RBC destruction. Peak oxygen uptake decreased by 0.31±0.16l min(-1) from PRE to POST (P=2×10(-4) ) but was not significantly altered at POST5 compared with PRE. Overall, these findings indicate that 4days of HDTBR does not increase RBC destruction and that re-examination of the time course and mechanisms of Hbmass alterations following short-term spaceflight and simulated microgravity is warranted.

Analogs of microgravity: head-down tilt and water immersion.

This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. DI is less common but well accepted for long-duration studies. Very few studies exist that attempt to validate a specific simulation mode against actual microgravity. Many fundamental physical, and thus physiological, differences exist between microgravity and our methods to simulate it, and between the different methods. Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability.

Caloric restriction diminishes the pressor response to static exercise.

BackgroundAstronauts in space consume fewer calories and return to earth predisposed to orthostatic intolerance. The role that caloric deficit plays in the modulation of autonomic control of the cardiovascular system is unknown. Therefore, the purpose of this study was to determine the effects of 6° head-down bedrest (an analog of spaceflight) with a hypocaloric diet (25 % caloric restriction) (CR) on autonomic neural control during static handgrip (HG) and cold pressor (CP) tests. Nine healthy young men participated in a randomized crossover bedrest (BR) study, consisting of four, two-week interventions (hypocaloric ambulatory, hypocaloric bedrest, normocaloric ambulatory, and normocaloric bedrest), each separated by 5 months. Heart rate (HR), arterial pressure, and muscle sympathetic nerve activity (MSNA) were recorded before, during, and after HG (40 % of maximum voluntary contraction to fatigue), post-exercise muscle ischemia (forearm occlusion), and CP. Bedrest and nutritional combinations were compared using two-way ANOVA with repeated measures.ResultsHR, MSNA, and the change in systolic blood pressure during HG were attenuated with caloric restriction, but post-intervention responses for all groups were similar during post-exercise muscle ischemia. CR was associated with a higher diastolic blood pressure during CP; however, HR was directionally opposite (i.e., increase with BR, decrease with CR).ConclusionsIn summary 14-day caloric/fat restriction attenuated MSNA and pressor responses during isometric exercise to fatigue but not to post-exercise muscle ischemia. This indicates that the integrity of the metaboreflex is maintained whereas the influence of the mechanoreflex and/or central command may be reduced.

Electromyography-based analysis of human upper limbs during 45-day head-down bed-rest

Muscle deconditioning occurs in response to simulated or actual microgravity. In spaceflight, astronauts become monkey-like for mainly using their upper limbs to control the operating system and to complete corresponding tasks. The changes of upper limbs׳ athletic ability will directly affect astronauts’ working performance. This study investigated the variation trend of surface electromyography (sEMG) during prolonged simulated microgravity. Eight healthy males participating in this study performed strict 45-day head-down bed-rest (HDBR). On the 5th day of pre-HDBR, and the 15th, the 30th and the 45th days of HDBR, the subjects performed maximum pushing task and maximum pulling task, and sEMG was collected from upper limbs synchronously. Each subject’s maximum volunteer contractions of both the tasks during these days were compared, showing no significant change. However, changes were detected by sEMG-based analysis. It was found that integrated EMG, root mean square, mean frequency, fuzzy entropy of deltoid, and fuzzy entropy of triceps brachii changed significantly when comparing pre-HDBR with HDBR. The variation trend showed a recovery tendency after significant decline, which is inconsistent with the monotonic variation of lower limbs that was proved by previous research. These findings suggest that EMG changes in upper limbs during prolonged simulated microgravity, but has different variation trend from lower limbs.

Effect of Simulated Microgravity and Lunar Gravity on Human Inspiratory Muscle Function: 'Selena-T' 2015 Study.

As a part of the multi-disciplinary "SELENA-T"-2015 Bed Rest Study, we investigated the pattern of inspiratory muscles fatigue in 22 healthy male subjects during incremental exercise test to exhaustion before and after 21days of hypokinesia evoked by bed rest. Hypokinesia consisted of head-down bed rest (HDBR) at a minus 6° angle, simulating microgravity present on orbiting spacecraft, in 10 subjects. The remaining 12 subjects spent the first 5days of hypokinesia in HDBR position and the subsequent 16days in head-up bed rest (HUBR) at a plus 9.6° angle, as a presumed analog of lunar gravity that is six times less than Earth's gravity. Maximal inspiratory pressure (MIP) and electromyograms (EMG) of the diaphragm (D), parasternal (PS), sternocleidomastoid (SCM), and scalene (S) muscles served as indices of inspiratory muscle function. Before both HDBR and HUBR, exercise decreased MIP and centroid frequency (fc) of EMG (D, PS, SCM, and S) power spectrum (p < 0.05). After 3weeks of HDBR, but not HUBR, inspiratory muscles fatigue was more expressed compared with control (p < 0.05). We conclude that HDBR lowers inspiratory muscles resistance to fatigue during high-intensity exercise while HUBR has no such effect. These changes may limit maximal ventilation and may contribute to exercise intolerance observed after prolonged simulated microgravity. The physiological mechanisms of respiratory muscle dysfunction after HDBR consist primarily of postural effects, and are not due only to hypokinesia.

Human metabolic responses to microgravity simulated in a 45-day 6° head-down tilt bed rest (HDBR) experiment

Metabolomics approaches could achieve accurate and comprehensive analysis in human space exploration.

REACTION OF THE CARDIOVASCULAR, SYSTEM TO ORTHOSTATIC TESTING DURING EXTENDED HEAD-DOWN BED REST AS A FUNCTION OF THE COUNTERMEASURES START DATE.

The cardiovascular system (CVS) and its regulation are highly vulnerable to limited physical activity equally on Earth and in space. Purpose of the work is to study mechanical cardiac reactions to the standing test during extended head-down bed rest (BR) as a function of countermeasures start date. Subjects were 9 male volunteers. To assess the bioelectrical activity of the heart. (ECG) and mechanical activity (echoECG), the standing test was conducted during baseline data collection, every 60 days in BR, and on day 60 of recovery. The results showed a nonlinear dependence of the CVS function on time in BR. Level of orthostatic stability and time for orthostatic stability recovery were largely dependent on the scope of countermeasures applied during BR.

Left ventricular remodeling during and after 60 days of sedentary head-down bed rest.

Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters,P< 0.001). Resting measures of LV volume and mass were ∼15% (P< 0.001) and ∼14% lower (P< 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values (P< 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.

Hypovolemic men and women regulate blood pressure differently following exposure to artificial gravity

In addition to serious bone, vestibular, and muscle deterioration, space flight leads to cardiovascular dysfunction upon return to gravity. In seeking a countermeasure to space flight-induced orthostatic intolerance, we previously determined that exposure to artificial gravity (AG) training in a centrifuge improved orthostatic tolerance of ambulatory subjects. This protocol was more effective in men than women and more effective when subjects exercised. We now determine the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned (furosemide) men and women on one day following 90 min of AG compared to a control day (90 min of head-down bed rest, HDBR). There were three major findings: a short bout of artificial gravity improved orthostatic tolerance of hypovolemic men (30 %) and women (22 %). Men and women demonstrated different mechanisms of cardiovascular regulation on AG and HDBR days; women maintained systolic blood pressure the same after HDBR and AG exposure while men's systolic pressure dropped (11 ± 2.9 mmHg) after AG. Third, as presyncopal symptoms developed, men's and women's cardiac output and stroke volume dropped to the same level on both days, even though the OTL test lasted significantly longer on the AG day, indicating cardiac filling as a likely variable to trigger presyncope. (1) Even with gender differences, AG should be considered as a space flight countermeasure to be applied to astronauts before reentry into gravity, (2) men and women regulate blood pressure during an orthostatic stress differently following exposure to artificial gravity and (3) the trigger for presyncope may be cardiac filling.

Transcutaneous electrical acupuncture stimulation as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans.

ObjectiveSpaceflight is associated with cardiovascular deregulation. However, the influence of microgravity on the cardiovascular system and its mechanisms and countermeasures remain unknown. Our previous studies have demonstrated that transcutaneous electrical acupuncture stimulation (TEAS) is effective in improving orthostatic tolerance (OT). The purpose of this study was to determine if TEAS treatment can attenuate cardiovascular deconditioning induced by a 4-day −6° head-down bed rest (HDBR).MethodsFourteen healthy male subjects were randomly allocated to a control group (control, n=6, 4 days HDBR without countermeasures) and a TEAS treatment group (TEAS, n=8, 4 days HDBR with TEAS at Neiguan (PC6) for 30 min each day for 4 consecutive days during HDBR). OT, plasma hormones, plasma volume and heart rate variability were assessed before and after HDBR. Cardiac function and cerebral blood flow were measured before, during and after HDBR.ResultsThe data showed that TEAS treatment mitigated the decrease in OT that was observed in the control group and cardiac function, alleviated autonomic dysfunction, and partially prevented plasma volume reduction after HDBR. Angiotensin II and aldosterone were significantly increased by 129.3% and 133.3% after HDBR in the TEAS group (p<0.05).ConclusionsThese results indicate that 30 min of daily TEAS treatment at PC6 is partially effective in maintaining OT, probably due to increased plasma volume-regulating hormones and activation of the peripheral sympathetic nervous system. TEAS treatment appears effective at reducing cardiovascular deconditioning induced by HDBR for 4 days.Trial registration numberNCT02300207.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

AbstractTo explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P&amp;lt; 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50 and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P&amp;lt; 0.05). Neither control nor CM groups showed significant differences in the pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG CMs.

Effects of Exercise and Nutrition on the Coagulation System During Bedrest Immobilization.

Immobilization in hospitalized medical patients or during simulation of spaceflight induced deconditioning has been shown to be associated with loss of muscle mass and bone. Resistance vibrating exercise (RVE) and/or high protein diet are countermeasures, which are capable of mitigating the adverse effects of immobilization. We investigated the effect of these countermeasures on the coagulation system. Two groups of volunteers, each of whom performed such countermeasures, were enrolled in the study. Volunteers, who did nothing while bed rested, served as controls.The berest and the intervention protocols were carried out at Clinique d’ Investigation, MEDES, Toulouse, France.Eleven healthy men volunteered for this randomized crossover study. The subjects underwent 21 day of 6° head down bed rest (HDBR) followed by a washout period of 4 months. The first group followed an exercise schedule using resistance-vibrating exercise (RVE group). The second group also used the RVE but complemented it with high-protein supplement diet (NeX group). The third group only did bed rest.The highly sensitive methods calibrated automated thrombography (CAT) and thrombelastometry (TEM) were applied to monitor hemostatic changes.In all 3 groups, the hemostatic system shifted toward hypocoagulability during bed rest. For example, peak and thrombin formation velocity (VELINDEX) reduced in this period. Interestingly, a tendency toward hypercoagulation was observed during re-ambulation. In all 3 groups, ttPeak and StartTail were reduced, and Peak and VELINDEX (except in the RVE group) were significantly higher in relation to baseline values.Influence of bed rest on the coagulation system in the 2 groups performing countermeasures (RVE and NeX group) was the same as in the control bed-rested group. Clotting does not seem to be worsened by prolonged immobilization, or by countermeasures such as RVE/exercise or high-protein supplementation during immobilization. Therefore, only hospitalized medical patients at an elevated risk for thrombosis should be treated with anticoagulants. However, clinicians have to be aware that the re-ambulation period following immobilization might be associated with an elevated risk of thrombotic events.

Evaluation of T-wave alternans activity under stress conditions after 5 d and 21 d of sedentary head-down bed rest

It is well known that prolonged microgravity leads to cardiovascular deconditioning, inducing significant changes in autonomic control of the cardiovascular system. This may adversely influence cardiac repolarization, and provoke cardiac rhythm disturbances. T-wave alternans (TWA), reflecting temporal and spatial repolarization heterogeneity, could be affected. The aim of this work was to test the hypothesis that 5 d and 21 d head-down (−6°) bed rest (HDBR) increases TWA, thus suggesting a higher underlying electrical instability and related arrhythmogenic risk.Forty-four healthy male volunteers were enrolled in the experiments as part of the European Space Agency’s HDBR studies. High-fidelity ECG was recorded during orthostatic tolerance (OT) and aerobic power (AP) tests, before (PRE) and after HDBR (POST). A multilead scheme for TWA amplitude estimation was used, where non-normalized and T-wave amplitude normalized TWA indices were computed. In addition, spectral analysis of heart rate variability during OT was assessed.Both 5 d and 21 d HDBR induced a reduction in orthostatic tolerance time (OTT), as well as a decrease in maximal oxygen uptake and reserve capacity, thus suggesting cardiovascular deconditioning. However, TWA indices were found not to increase. Interestingly, subjects with lower OTT after 5 d HDBR also showed higher TWA during recovery after OT testing, associated with unbalanced sympathovagal response, even before the HDBR. In contrast with previous observations, augmented ventricular heterogeneity related to 5 d and 21 d HDBR was not sufficient to increase TWA under stress conditions.

Effect of Simulated Microgravity on Human Brain Gray Matter and White Matter--Evidence from MRI.

BackgroundThere is limited and inconclusive evidence that space environment, especially microgravity condition, may affect microstructure of human brain. This experiment hypothesized that there would be modifications in gray matter (GM) and white matter (WM) of the brain due to microgravity.MethodEighteen male volunteers were recruited and fourteen volunteers underwent -6° head-down bed rest (HDBR) for 30 days simulated microgravity. High-resolution brain anatomical imaging data and diffusion tensor imaging images were collected on a 3T MR system before and after HDBR. We applied voxel-based morphometry and tract-based spatial statistics analysis to investigate the structural changes in GM and WM of brain.ResultsWe observed significant decreases of GM volume in the bilateral frontal lobes, temporal poles, parahippocampal gyrus, insula and right hippocampus, and increases of GM volume in the vermis, bilateral paracentral lobule, right precuneus gyrus, left precentral gyrus and left postcentral gyrus after HDBR. Fractional anisotropy (FA) changes were also observed in multiple WM tracts.ConclusionThese regions showing GM changes are closely associated with the functional domains of performance, locomotion, learning, memory and coordination. Regional WM alterations may be related to brain function decline and adaption. Our findings provide the neuroanatomical evidence of brain dysfunction or plasticity in microgravity condition and a deeper insight into the cerebral mechanisms in microgravity condition.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

AbstractThe aim of this study is to explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P&lt; 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50, and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P&lt; 0.05). Neither control nor CM groups showed significant differences in pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG countermeasures.

Structural Brain Changes following Long-Term 6° Head-Down Tilt Bed Rest as an Analog for Spaceflight.

Following long-term spaceflight, a subset of the National Aeronautics and Space Administration astronauts present with visual impairment and increased intracranial pressure, known as visual impairment and intracranial pressure syndrome. We investigated structural brain changes following long-term head-down tilt bed rest as a spaceflight analog. Volumetric analysis was performed on structural pre- and post-bed rest brain MR images. Comparing post-bed rest to pre-bed rest images, we found the following: 1) no significant group differences in GM, WM, CSF, or ventricular volumes; 2) shift of the center of mass of the brain upward and posterior rotation of the brain relative to the skull; 3) a significant correlation between posterior brain rotation and changes in ventricular volume; and 4) significant increases in brain tissue density in regions at the vertex, including the frontoparietal lobes, with contraction of adjacent extra-axial CSF spaces, and significant decreases in tissue density in areas along the base of the brain, including the orbitofrontal cortex. We observed widespread morphologic changes with brain tissue redistribution in response to gravity changes; possible associated functional changes are unknown. The observation that ventricular change is correlated to posterior brain rotation suggests an alteration in CSF homeostasis. Ultimately, to elucidate any structural changes that may play a role in visual impairment and intracranial pressure syndrome, volumetric analysis of pre- and postflight structural scans of astronauts is needed.

Influence of bed rest on plasma galanin and adrenomedullin at presyncope.

The role of hormones in reduced orthostatic tolerance following long-term immobilization remains uncertain. We have previously shown that plasma concentrations of adrenomedullin and galanin, two peptides with vasodepressor properties, rise significantly during orthostatic challenge. We tested the hypothesis that bedrest immobilization increases the rise in adrenomedullin and galanin during orthostatic challenge leading to presyncope. We measured baseline (supine), presyncope and recovery (10min postpresyncope, supine) levels of adrenomedullin and galanin in 8 healthy men, before and after 21days of -6° head-down bed rest (HDBR). Presyncope was elicited using a combined head-up tilt and graded lower body negative pressure protocol. Orthostatic tolerance was defined as the time taken from the commencement of head-up tilt to the development of presyncope. Orthostatic tolerance time after HDBR reduced by 8·36±5·39min (P=0·0032). HDBR increased plasma adrenomedullin concentration to orthostatic challenge (P=0·0367). Compared to pre-HDBR, a significant rise in post-HDBR presyncopal (P<0·001) and recovery adrenomedullin concentration (P<0·01) was demonstrated. In contrast, we observed no change in pre- and post-HDBR galanin levels to orthostatic challenge. Bedrest immobilization appears to affect adrenomedullin levels in that greater increases in adrenomedullin occur at presyncope following bedrest immobilization. Due to its peripheral vasculature hypotensive effect, the greater levels of adrenomedullin at presyncope following bedrest immobilization may have contributed to the reduced orthostatic capacity postbedrest.

Microgravity Simulated by the 6° Head-Down Tilt Bed Rest Test Increases Intestinal Motility but Fails to Induce Gastrointestinal Symptoms of Space Motion Sickness.

Space motion sickness (SMS) is the most relevant medical problem during the first days in microgravity. Studies addressing pathophysiology in space face severe technical challenges and microgravity is frequently simulated using the 6° head-down tilt bed rest test (HDT). We were aiming to test whether SMS could be simulated by HDT, identify related changes in gastrointestinal physiology and test for beneficial effects of exercise interventions. HDT was performed in ten healthy individuals. Each individual was tested in three study campaigns varying by a 30-min daily exercise intervention of either standing, an upright exercise regimen, or no intervention. Gastrointestinal symptoms, stool characteristics, gastric emptying time, and small intestinal transit were assessed using standardized questionnaires, (13)C octanoate breath test, and H2 lactulose breath test, respectively, before and at day 2 and 5 of HDT. Individuals described no or minimal gastrointestinal symptoms during HDT. Gastric emptying remained unchanged relative to baseline data collection (BDC). At day 2 of HDT the H₂ peak of the lactulose test appeared earlier (mean ± standard error for BDC-1, HDT2, HDT5: 198 ± 7, 139 ± 18, 183 ± 10 min; p: 0.040), indicating accelerated small intestinal transit. Furthermore, during HDT, stool was softer and stool mass increased (BDC: 47 ± 6, HDT: 91 ± 12, recovery: 53 ± 8 g/day; p: 0.014), indicating accelerated colonic transit. Exercise interventions had no effect. HDT did not induce symptoms of SMS. During HDT, gastric emptying remained unchanged, but small and large intestinal transit was accelerated.

5-Day Bed Rest: Portal and Lower Limb Veins With and Without Artificial Gravity Countermeasures

The objective of the study was to evaluate the effect of short-term, head-down bed rest (HDBR), with and without artificial gravity countermeasures, on splanchnic and lower limb vein properties. Data were collected from 12 men before and after 5 d of continuous -6° HDBR without countermeasures (CON) and with two artificial gravity countermeasure protocols: 30-min continuous centrifugation (AG1), and 30-min intermittent centrifugation (AG2). Portal (PV), tibial (TibV), and gastrocnemius (GastV) veins were investigated by echography supine and after 30 min of head-up tilt. After HDBR, there was no change in PV, TibV, or GastV cross-sectional area at rest in any of the three conditions. In response to tilt, GastV and TibV area increased (168±141% and 192±124%, respectively) with no change in this response post-HDBR in any of the experimental conditions (P>0.05). PV area decreased with tilt (-33±13%) and was not different pre- to post-HDBR in the CON or AG1 conditions. However, there was a greater reduction in PV area in the AG2 group post-HDBR (-32±10% pre, -49±9% post-HDBR, P=0.003). Calf veins were not significantly affected by 5 d of HDBR and did not appear to be negatively impacted by the artificial gravity countermeasures over this time period. In addition, the intermittent protocol resulted in better splanchnic vasoconstriction in response to head-up tilt, which may have contributed to a better maintenance of orthostatic tolerance post-HDBR.