Head-down Tilt Bed Rest Research Articles

Rowing Ergometer Training During Five Weeks of Head-Down Tilt Bedrest Preserves Cardiac Work and LV Mass

Exercise training in space or during bedrest which recruits both upper and lower body muscle groups may preserve cardiac work and thereby LV structure. PURPOSE: Examine whether rowing ergometry via a periodized exercise training program will not only preserve but increase cardiac work and LV mass. METHODS: Fifteen subjects (14 men and 1 woman, age 20-55 yr) were studied before, during and immediately after 5 weeks of −6° head-down tilt (HDT) bed rest. The subjects were divided into two groups: (1) bed rest without exercise, but sitting upright 45 minutes/day quietly on the ergometer (n=3); (2) bed rest with exercise (30-45 minutes/day, 6 days/week of exercise on a rowing ergometer in addition to 2 days/week of supine resistance training) (n=12). The endurance training included three days of exercise at a moderate, base pace and two days of high intensity interval training followed by a recovery day of intensity below base pace. Ambulatory systolic blood pressure and heart rate were measured over 24 hours before, during and after bed rest (Suntech Accutracker). Stroke volume was measured via acetylene rebreathing technique. Cardiac work was calculated as a product of stroke volume, heart rate, systolic blood pressure and time. RESULTS: Cardiac work of subjects who trained during bed rest was maintained to levels measured prior to bed rest (7.64 + 3.02 vs. 7.71 + 2.14, e08ml·mmHg·day−1). However, the cardiac work of nonexercising subjects decreased during bed rest (7.70 + 1.45 vs. 6.46 + 0.79, e08ml·mmHg·day−1). LV mass was preserved among the exercisers (154 + 58 vs. 157 + 50mg) yet decreased in the non-exercising group (124 + 10 vs. 117 + 1mg). CONCLUSIONS: Cardiac work was preserved in subjects who performed 30-45 min/day of dynamic, rowing exercise combined with resistance training during HDT bed rest. This preservation of cardiac work prevented the cardiac atrophy associated with 5 weeks of bed rest deconditioning. Supported by NASA grant CA00701.

WISE‐2005: Lower Body Negative Pressure Treadmill and Resistive Exercise Countermeasures Maintain Physiologic Function in Women during 60‐days of Simulated Microgravity

INTRODUCTION: We hypothesized that supine LBNP treadmill exercise combined with Flywheel resistive exercise maintains upright physiologic responses following 60‐days of head‐down tilt (HDT) bed rest (BR). METHODS: 16 healthy women (age 25–40 years) underwent 60‐days HDT (‐6°) BR. Women were assigned to either a non‐exercise control group (CON, n=8) or to an exercise group (EX, n=8). EX subjects performed a 40‐min, variable intensity LBNP exercise protocol at foot‐ward forces between 1.0–1.1 times body weight, followed by 10‐min of resting LBNP 3–4 days/week. Resistive exercise of maximal concentric and eccentric supine leg press and heel raise exercises were performed using a flywheel ergometer 2–3 days/week. IRBs approved this study with informed/written consent. RESULTS: Post‐BR VO2pk was not different in EX (−3.3±1.2%) but decreased significantly in CON (−21.2±2.1%), p< 0.05. Post‐BR orthostatic tolerance time (mean±se) decreased significantly less in EX (19.3±1.3 to 14.4±1.5 min) than in CON (17.5±0.1 to 9.1±1.5 min), p=0.03. Post‐BR muscle strength decreased significantly in CON, but was preserved in EX. Post‐BR bone resorption was greater than pre‐BR in both groups (p<0.05). Bone formation markers, were significantly elevated (p<0.05) in EX than in CON. CONCLUSIONS: Supine LBNP treadmill exercise along with flywheel resistive exercise maintains upright exercise capacity, orthostatic responses and muscle strength during 60‐days HDT BR. Supported by ESA, CSA, CNES; and NASA: NNJ04HF71G and NNJ04HF72G.

Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long‐term bed rest with and without countermeasures

The cellular mechanisms of human skeletal muscle adaptation to disuse are largely unknown. The aim of this study was to determine the morphological and biochemical changes of the lower limb soleus and vastus lateralis muscles following 60 days of head-down tilt bed rest in women with and without exercise countermeasure using molecular biomarkers monitoring functional cell compartments. Muscle biopsies were taken before (pre) and after bed rest (post) from a bed rest-only and a bed rest exercise group (n = 8, each). NOS1 and NOS3/PECAM, markers of myofibre 'activity' and capillary density, and MuRF1 (E3 ubiquitin-ligase), a marker of proteolysis, were documented by confocal immunofluorescence and immunoblot analyses. Morphometrical parameters (myofibre cross-sectional area, type I/II distribution) were largely preserved in muscles from the exercise group with a robust trend for type II hypertrophy in vastus lateralis. In the bed rest-only group, the relative NOS1 immunostaining intensity was decreased at type I and II myofibre membranes, while the bed rest plus exercise group compensated for this loss particularly in soleus. In the microvascular network, NOS3 expression and the capillary-to-fibre ratio were both increased in the exercise group. Elevated MuRF1 immunosignals found in subgroups of atrophic myofibres probably reflected accelerated proteolysis. Immunoblots revealed overexpression of the MuRF1 protein in the soleus of the bed rest-only group (> 35% vs. pre). We conclude that exercise countermeasure during bed rest affected both NOS/NO signalling and proteolysis in female skeletal muscle. Maintenance of NO signalling mechanisms and normal protein turnover by exercise countermeasure may be crucial steps to attenuate human skeletal muscle atrophy and to maintain cell function following chronic disuse.

Neuroendocrine and Immune Responses to 16-Day Bed Rest with Realistic Launch and Landing G Profiles

Spaceflight is associated with increased glucocorticoids and catecholamines, both well-known for their immunosuppressive effects. The objective of this study was to develop a model of spaceflight by using a human centrifuge to reproduce launch and landing G forces along with bed rest to simulate microgravity. Acute changes in G forces are causal factors in neuroendocrine and immune changes. Ten subjects underwent realistic launch G-force profiles followed by 16 d of 60 head-down tilt bed rest. At the end of the bed rest, subjects were subjected to realistic landing G-force profiles. Stress hormones and changes in leukocyte and lymphocyte subsets were measured in blood and urine samples over the course of the study. Similar to shorter Shuttle missions (i.e., < or = 9 d), plasma cortisol was significantly decreased at simulated landing while urinary epinephrine was significantly increased. Urinary cortisol was significantly increased after simulated launch. The pattern of leukocyte and lymphocyte changes also mirrored the changes found in shorter 9-d spaceflights. These data suggest a role for both catecholamines and glucocorticoids in mediating changes in leukocyte and lymphocyte subsets during simulated microgravity coupled with hypergravity. Our results were also strikingly similar to those from actual Shuttle missions and support our conclusion that we have developed a model of spaceflight.

Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.

Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance

Orthostatic intolerance follows actual weightlessness and weightlessness simulated by bed rest. Orthostasis immediately after acute exercise imposes greater cardiovascular stress than orthostasis without prior exercise. We hypothesized that 5 min/day of simulated orthostasis [supine lower body negative pressure (LBNP)] immediately following LBNP exercise maintains orthostatic tolerance during bed rest. Identical twins (14 women, 16 men) underwent 30 days of 6 degrees head-down tilt bed rest. One of each pair was randomly selected as a control, and their sibling performed 40 min/day of treadmill exercise while supine in 53 mmHg (SD 4) [7.05 kPa (SD 0.50)] LBNP. LBNP continued for 5 min after exercise stopped. Head-up tilt at 60 degrees plus graded LBNP assessed orthostatic tolerance before and after bed rest. Hemodynamic measurements accompanied these tests. Bed rest decreased orthostatic tolerance time to a greater extent in control [34% (SD 10)] than in countermeasure subjects [13% (SD 20); P < 0.004]. Controls exhibited cardiac stroke volume reduction and relative cardioacceleration typically seen after bed rest, yet no such changes occurred in the countermeasure group. These findings demonstrate that 40 min/day of supine LBNP treadmill exercise followed immediately by 5 min of resting LBNP attenuates, but does not fully prevent, the orthostatic intolerance associated with 30 days of bed rest. We speculate that longer postexercise LBNP may improve results. Together with our earlier related studies, these ground-based results support spaceflight evaluation of postexercise orthostatic stress as a time-efficient countermeasure against postflight orthostatic intolerance.

Cardiac atrophy in women following bed rest

Both chronic microgravity exposure and long‐duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to post‐spaceflight presyncope and orthostatic hypotension than male astronauts, most previous high‐resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1±4 years) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6° head‐down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n=8) or two treatment groups consisting of (1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n=8), or (2) protein (0.45 g/kg/day increase) plus branched‐chain amino acid (BCAA) (7.2 g/day) supplementation (n=8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96±26–77±25 mL; P=0.03) and RV volumes (104±33–86±25 mL; P=0.02), LV (2.2±0.2–2.0±0.2 g/kg; P=0.003) and RV masses (0.8±0.1–0.6±0.1 g/kg; P&lt;0.001), and the length of the major axis of the LV (90±6–84±7 mm. P&lt;0.001), similar to what has been observed previously in men (8.0%; Perhonen M.A., Franco F., Lane L.D., Buckey J.C., Blomqvist Zerwekh J.E., Peshock R.M., Weatherall P.T., Levine B.D. J Appl Physiol 2001: 91: 645–653). In contrast, there were no significant reductions in LV or RV volumes in the exercise‐trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9±0.4–2.3±0.3 g/kg; P&lt;0.001) and RV masses (0.7±0.1–0.8±0.2 g/kg; P=0.002), as well as mean wall thickness (9±2–11±1 mm; P=0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P&lt;0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103±14–80±16 mL; P=0.02) and major‐axis length (91±5–88±7 mm; P=0.003). All subjects lost an equivalent amount of body mass (3.4±0.2 kg control; 3.1±0.04 kg exercise; 2.8±0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.

Rowing Ergometer Training During Five Weeks of Head Down Tilt Bedrest Preserves Upright Exercise Capacity

Adaptation to real or simulated microgravity leads to a reduction in maximal exercise capacity in the upright position. Although exercise training in space or during bedrest may preserve supine work capacity, few sustained interventions have successfully maintained upright exercise capacity. PURPOSE: Examine the efficacy of rowing ergometry via a periodized exercise training program in preserving upright exercise capacity. METHODS: Five subjects (4 men and 1 woman, age 21–55 yr) were studied before and immediately after 5 weeks of-6° head-down tilt (HDT) bed rest. The subjects were divided into two groups: (1) bed rest without exercise, but sitting upright 45 minutes/day quietly on the ergometer (n=2), (2) bed rest with exercise (30–45 minutes/day, 6 days/ week of exercise on a rowing ergometer in addition to 2 days/week of supine resistance training) (n=3). The endurance training included three days of exercise at a moderate, base pace and two days of high intensity interval training followed by a recovery day of intensity below base pace. VO2max was measured before and after bed rest with an incremental protocol on an upright cycle ergometer until exhaustion. Gas fractions were measured by mass spectrometer, ventilation via Tissot spyrometer for the calculation of VO2 (Douglas bag method) and heart rate via electrocardiogram (Schiller). RESULTS: VO2max of subjects who trained during bed rest were maintained at pre-bed rest levels (2.42+ 0.51 vs. 2.58 + 0.51 L/min;28.4+ 1.9 vs. 32.1 + 5. 5 ml/kg/min). However, VO2max of nonexercising subjects decreased by 18% following bed rest (2.56 + 0.31 vs. 2.08 + 0.14L/min; 39.4 + 0.0 vs. 32.2 + 2.9 ml/kg/min). This differential response between the 2 groups appeared significant (preliminary interaction p=0.03). Upright maximal work rate was preserved in the trained subjects (215 + 76 vs. 222 + 64 Watts) but reduced in the sedentary subjects by 16%(223 + 4vs. 188+ 18 Watts). CONCLUSIONS: Upright work capacity and VO2max are maintained in subjects who perform 30–45 min/day of dynamic, rowing exercise combined with resistance training during HDT bed rest.

LBNP treadmill exercise maintains spine function and muscle strength in identical twins during 28-day simulated microgravity

The purpose of this study was to determine whether lower body negative pressure (LBNP) treadmill exercise maintains lumbar spinal compressive properties, curvature, and back muscle strength after 28 days of 6 degrees head-down tilt (HDT) bed rest (BR). We hypothesize that LBNP treadmill exercise will maintain lumbar spine compressibility, lumbar lordosis and back muscle strength after 28 days of 6 degrees HDT bed rest. Fifteen healthy identical twin pairs (14 women and 16 men) participated in this study. One identical twin was randomly assigned to the nonexercise control (Con) group, and their sibling was assigned to the exercise (Ex) group. The lumbar spine was significantly more compressible Post-BR compared with Pre-BR in the Con (P=0.01). Lumbar spine compressibility Post-BR was not significantly different compared with Pre-BR in the Ex group (P=0.89). In both the Con and Ex groups, there were no significant changes Post-BR in lumbar lordosis compared with Pre-BR. Back muscle strength significantly decreased in the Con group Post-BR (P=0.002), whereas in the Ex group back muscle strength was not significantly different from Pre-BR values. A significant increase in lumbar spine compressibility in the Con group suggests that spinal deconditioning to gravity occurs during 28-day bed rest. Changes in the mechanical properties of the lumbar spine may be an early indicator of lumbar intervertebral disk degeneration. Supine LBNP treadmill exercise provides axial loads to the lumbar spine and may prevent lumbar spine deconditioning associated with HDT bed rest.

Cardiac atrophy in women following bed rest

Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.

Microgravity and cardiac atrophy: no sex discrimination

mans’ continued initiative in space exploration will tax the human body, including the cardiovascular system. This system is exquisitely sensitive to loading conditions and neurohormonal stimuli and is adapted to function in normal gravitational environments (1 G). Both mechanical (muscle and

Effect of unloading on muscle volume with and without resistance training

The present study aimed to investigate the effect of resistance training on the volume of four muscle groups and/or 17 individual muscles of the human lower limb during 20 days of 6 ∘ head-down tilt bed rest. Twelve healthy men were divided into two groups: the resistance training group: BR-Tr ( n = 6 ) and the control group: BR-Cont ( n = 6 ) . The volumes of the knee extensor, knee flexor, adductor, plantar flexor, and dorsiflexor muscle groups and their individual muscles were calculated. After the bed rest, the BR-Tr subjects showed no significant change in the volume in almost all tested muscles; in contrast, the volumes of the four muscle groups significantly decreased in the BR-Cont group ( - 12 % to - 8 %). These results suggest that resistance training during bed rest can prevent the deteriorating of thigh muscles and calf muscles.

Bed rest and immunity

Space flight has been shown to result in altered immune responses. The current study was designed to investigate this possibility by using the bed rest model of some space flight conditions. A large number of women are included as subjects in the study. The hypothesis being tested is: 60 days head-down tilt bed rest of humans will affect the immune system and resistance to infection. Blood, urine and saliva samples will be obtained from bed rest subjects prior to, at intervals during, and after completion of 60 days of head-down tilt bed rest. Leukocyte blastogenesis, cytokine production and virus reactivation will be assessed. The ability of the subjects to respond appropriately to immunization with the neoantigen bacteriophage φ X-174 will also be determined. Bed rest is being carried out at MEDES, Toulouse France, and the University of Texas Medical Branch, Galveston, TX. The studies to be carried out in France will also allow assessment of the effects of muscle/bone exercise and nutritional countermeasures on the immune system in addition to the effects of bed rest.

Diastolic Untwisting is Impaired following Bed Rest

Bed rest deconditioning leads to physiologic cardiac atrophy which may compromise cardiac filling by reducing diastolic untwisting. PURPOSE: To test the hypothesis that diastolic untwisting is impaired by head-down tilt bed rest but preserved by exercise training while confined to strict bed rest. METHODS: We performed myocardial tagged MRI and calculated max untwisting rates of the endocardium, midwall, and epicardium by Harmonic Phase Analysis (HARP) immediately before and after 18 days of strict −6° head-down tilt (HDT) bed rest with (N=10) and without exercise (N=5). The exercise group cycled on a supine ergometer for 30 minutes, 3 times a day at 75% of their max heart rate in order to normalize cardiac work compared to ambulatory periods. RESULTS: After strict bed rest without exercise, there was a significant reduction in the average max untwisting rates of the midwall (−52.3 degrees/sec to −35.2 degrees/ sec, P=0.03). In contrast, when exercise was performed in bed, untwisting rates were preserved or even enhanced (−39.2 degrees/sec to −59.0 degrees/sec, P=0.03). The differential response was significant between groups (interaction P=0.01), particularly at the midwall where untwisting is most reliably measured. CONCLUSIONS: Diastolic untwisting is impaired after sedentary short term HDT bed rest while bed rest with exercise can prevent the physiologic cardiac remodeling/ atrophy associated with bed rest and preserve diastolic suction.Table

Why Is Orthostatic Tolerance Lower in Women than in Men? Renal and Cardiovascular Responses to Simulated Microgravity and the Role of Midodrine

BackgroundExposure to microgravity induces cardiovascular deconditioning, manifested by orthostatic intolerance (OI). We assessed the renal, cardioendocrine, and cardiovascular responses of women and men to simulated microgravity to examine the impact...

WISE‐2005: Exercise countermeasure protects against changes in cardiovascular response to sublingual nitroglycerin after 56‐d bed rest

Cardiovascular responses to 0.3mg sublingual nitroglycerin spray (NG) were assessed before and after 56 days head-down tilt bed rest (HDT) with (EX) and without (No-EX) treadmill in LBNP and resistive exercise countermeasure. Heart rate (HR), mean arterial pressure (MAP, finger photoplethysmography), and aortic blood velocity (pulse Doppler ultrasound) were recorded before and after administration of NG. In response to NG stimulation pre HDT, MAP decreased by 5.5±3.3mmHg (mean±SD), and HR increased by 12±4bpm. The increase in HR, combined with a small increase in cardiac stroke volume (SV), resulted in cardiac output (CO) increasing by 0.97±0.55L/min. Post HDT, a trend was observed to higher resting HR and lower MAP in No-EX. Responses to NG were similar to the pre HDT condition, however, No-EX showed an augmented HR increase (11±8bpm) when compared to EX (7±4bpm, p=0.035). As SV did not change from the pre HDT condition, the increased HR response resulted in increased CO. MAP responses were similar in both groups post HDT; therefore, it would appear that No-EX had a greater reliance on the heart rate component of blood pressure regulation. This is likely the result of increased vasodilation and or lack of compensatory sympathetic vasoconstriction in the peripheral vasculature. The results of this study suggest that exercise protects against cardiovascular changes during HDT that would alter responses to NG stimulation. Supported by Canadian Space Agency, NASA, ESA, CNES

Effects of acid base balance on bone metabolism in bed rest subjects as an analog for space flight

As mission durations increase, the long-term effects of weightlessness on the deterioration of the skeleton are inevitable, and countermeasures must be developed. Previous studies show that diet and acid-base balance can affect bone loss during simulated weightlessness (bed rest)(AJCN, 80:1058). The present study was to evaluate effects of acid-base balance on bone after 60–90 days of −6° head-down tilt bed rest. A total of 11 subjects participated (8 M, 3 F; age 26–55 y) in the study. Blood and urine were collected twice before and once per month of bed rest. Urine samples were analyzed for n-telopeptide (NTX), pyridinium crosslinks (PYD), deoxypridinoline (DPD), sulfate, and pH. Data were analyzed using repeated measures ANOVA and Pearson correlation coefficients determined. Similar to space flight, markers of bone resorption increased during bed rest. Significant correlations were recorded between urinary sulfate and NTX (r=0.72), PYD (r=0.78), DPD (r=0.72) (p<0.01 for all). Urine pH (both 2nd void and 24 hr pool) was negatively correlated with the percent change in NTX from pre-bed rest (p<0.01). These data suggest that factors such as diet, urinary pH, and sulfur metabolism are related to bone metabolism during bed rest. The effects of acid-base balance on bone metabolism during bed rest may have significant implications for bone health in space flight and on Earth. This project was supported by the NASA Flight Analogs/Bed Rest Research Project.

WISE‐2005: 60 days head‐down bed rest causes a shift towards a pro‐atherosclerotic environment

This study reports on the first 12 subjects of the Women International Space Simulation for Exploration (WISE) who completed 60 days of head-down tilt (HDT) bed rest to test exercise and nutrition countermeasures compared to controls. We hypothesized that exercise would prevent an increase in pro-atherosclerotic factors associated with the inactivity of bed rest. Blood samples were collected before and at the end of bed rest to examine the difference in angiotensin II (ANG II), adhesion molecules (ICAM, VCAM, and e-SEL), and nitric oxide metabolites (NOmet), among others. ANG II was increased in both of the non-exercising groups (nutrition and control combined increased from 11.34±2.2pg/ml to 25.5±5.5pg/ml) but not in the exercise group (16.1±3.9pg/ml and 14.1±3.6pg/ml). ICAM and e-SEL showed no change; however VCAM increased in the non-exercising groups after the bed rest (584.8±23.8ng/ml and 630.2±17.0ng/ml). ANG II is known to increase the formation of reactive oxygen species (ROS), and may be a reason for the decrease seen in the levels of NOmet in the non-exercising groups (40.1±3.4μM and 26.5±3.8μM) but not in the exercising group (50.98±9.73μM to 47.88±5.21μM). 60 days of bed rest in HDT causes a shift in some factors towards a pro-atherosclerotic state while regular exercise during the bed rest prevented these changes. Supported by Canadian Space Agency, NASA, ESA, CNES

Blood volume measurement: The comparison of pulse dye densitometry and Dill and Costill's methods

In many clinical situations, it is crucial to determine circulating blood volume (BV) easily and to repeat this measurement. The Dye DensitoGram Analyzer® (DDG, Nihon Kohden Corp) measures semi-automatically BV, using an injection of IndoCyanine Green (ICG, 10 mg), and avoiding intermittent blood samples. The DDG was used during a 90-day microgravity simulation by Head-Down-Tilt bed rest (HDT) to measure BV and compared with the calculation of the plasma volume (PV) variations according to Dill and Costill's formula (DC). Seventeen healthy volunteers were included: 8 control subjects (Co) and 9 subjects submitted to a resistive exercise counter-measure (CM). Measurements were performed, one day before HDT, on days 3 and 90 of HDT and on day 9 after HDT. A double measurement of the BV was performed to assess the repeatability of this method. On the last day of HDT a significant decrease ( p < 0.05) in the PV was noted with the DDG (Co: − 12.3 ± 5.7%, CM: − 9.0 ± 5.3%) and DC; (Co: − 4.7 ± 1.8%, CM: − 6.8 ± 2.5%). A good repeatability of the technique was shown with a low intrasubjects coefficient of variation (4.95 ± 0.95%) and an acceptable intersubjects coefficient of variation (15.30 ± 1.13%). No correlation was noted between DDG and DC ( r 2 = 0.27). The DDG gives a good repeatability, not affected by the microgravity exposure. Thanks to its capacity to measure accurately the BV within 7–10 min, this device presents major advantages for clinical use and research purpose.

Portal vein cross-sectional area and flow and orthostatic tolerance: a 90-day bed rest study.

The objective of this study was to evaluate the changes in the portal vein cross-sectional area (PV CSA) and flow during a stand test associated with orthostatic intolerance. Eighteen subjects underwent a 90-day head-down tilt (HDT) bed rest at 6 degrees: 9 controls (Con) and 9 with flywheel exercise countermeasures (CM). At post-HDT, nine subjects (5 CM, 4 Con) were tolerant, and nine were intolerant. The PV CSA was measured by echography. We found that at HDT day 85, the PV CSA at rest had increased less in the CM subjects than in the Con (+12 vs. +27% from pre-HDT supine; P < 0.05), whereas it increased similarly in tolerant and intolerant subjects (23 and 16%, respectively). Two days after the HDT, there was a decrease in the PV CSA supine compared with the pre-HDT PV CSA supine that was similar for all groups (Con: -11%, CM: -21%; tolerant: -10%, intolerant: -16%; P < 0.05). The PV CSA decreased significantly less from supine to standing in the Con than in the CM group (-2 vs. -10% compared with the pre-HDT stand test; P < 0.05). The PV CSA also decreased significantly from supine to standing compared with the pre-HDT stand test in the tolerant group but not in the intolerant group (-20 vs. +2%; P < 0.05). From these findings, we conclude the following. 1) Because the portal vein is the only output from the splanchnic vascular area, we suggest that the lower reduction in the PV CSA and flow associated with orthostatic intolerance was related to a lower splanchnic arterial vasoconstriction. 2) The flywheel exercise CM helped to reduce the distention of the splanchnic network at rest and to maintain partially the splanchnic vasoconstriction, but it did not reduce the orthostatic intolerance.