Changes in lower extremity muscle function after 56 days of bed rest

Preservation of muscle function, known to decline in microgravity and simulation (bed rest), is important for successful spaceflight missions. Hence, there is great interest in developing interventions to prevent muscle-function loss. In this study, 20 males underwent 56 days of bed rest. Ten volunteers were randomized to do resistive vibration exercise (RVE). The other 10 served as controls. RVE consisted of muscle contractions against resistance and concurrent whole-body vibration. Main outcome parameters were maximal isometric plantar-flexion force (IPFF), electromyography (EMG)/force ratio, as well as jumping power and height. Measurements were obtained before and after bed rest, including a morning and evening assessment on the first day of recovery from bed rest. IPFF (-17.1%), jumping peak power (-24.1%), and height (-28.5%) declined (P < 0.05) in the control group. There was a trend to EMG/force ratio decrease (-20%; P = 0.051). RVE preserved IPFF and mitigated the decline of countermovement jump performance (peak power -12.2%; height -14.2%). In both groups, IPFF was reduced between the two measurements of the first day of reambulation. This study indicates that bed rest and countermeasure exercises differentially affect the various functions of skeletal muscle. Moreover, the time course during recovery needs to be considered more thoroughly in future studies, as IPFF declined not only with bed rest but also within the first day of reambulation. RVE was effective in maintaining IPFF but only mitigated the decline in jumping performance. More research is needed to develop countermeasures that maintain muscle strength as well as other muscle functions including power.     

Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest.

This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a -6 degrees head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 +/- 158 vs. 663 +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by approximately 16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.     

Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle

The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest. Twelve young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from six of the subjects prior to, immediately after, and 3 h after 45 min of one-legged knee extensor exercise performed before and after bed rest. Maximal oxygen uptake decreased by 4%, and exercise endurance decreased nonsignificantly, by 11%, by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ～45%, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity ～8%, and miR-1 and miR-133a content ～10%. However, cytochrome c and vascular endothelial growth factor (VEGF) protein content as well as capillarization did not change significantly with bed rest. Acute exercise increased AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor-γ coactivator-1α, and VEGF mRNA content in skeletal muscle before bed rest, but the responses were abolished after bed rest. The present findings indicate that only 7 days of physical inactivity reduces skeletal muscle metabolic capacity as well as abolishes exercise-induced adaptive gene responses, likely reflecting an interference with the ability of skeletal muscle to adapt to exercise.     

Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.     

Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (W(max))] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger (P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger (P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser2?3, Ser2?? and Ser3??, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.     

WISE 2005: chronic bed rest impairs microcirculatory endothelium in women

Sedentary behavior has deleterious effects on the cardiovascular system, including reduced endothelial functions. A 2-mo bed rest study in healthy women [women international space simulation for exploration (WISE) 2005 program] presented a unique opportunity to analyze the specific effects of prolonged inactivity without other vascular risk factors on the endothelium. We investigated endothelial properties before and after 56 days of bed rest in 8 subjects who performed no exercise (control group: No-EX) and in 8 subjects who regularly performed treadmill exercise in a lower body negative pressure chamber as well as resistance exercise (countermeasure group, EX). A functional evaluation of the microcirculation in the skin was assessed with laser Doppler. We studied endothelium-dependent and -independent vasodilation using iontophoresis of acetylcholine and sodium nitroprusside, respectively. We also measured circulating endothelial cells (CECs), an index of endothelial damage. In the No-EX group, endothelium-dependent vasodilation was significantly reduced (35.4 +/- 4.8% vs. 24.1 +/- 3.8%, P < 0.05) by bed rest with a significant increase in the number of CECs (3.6 +/- 1.4 vs. 10.6 +/- 2.7 ml(-1), P < 0.05). In the EX group, endothelium-dependent vasodilation and number of CECs were preserved. Our study shows that in humans prolonged bed rest causes impairment of endothelium-dependent function at the microcirculatory level, along with an increase in circulating endothelial cells. Microcirculatory endothelial dysfunction might participate in cardiovascular deconditioning, as well as in several bed rest-induced pathologies. We therefore conclude that the endothelium should be a target for countermeasures during periods of prolonged deconditioning.     

Maximal and submaximal forces of slow fibers in human soleus after bed rest.

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (P(o)), maximum activated force (F(max)) per cross-sectional area (CSA), and the common-logarithm value of free Ca(2+) concentration required for half-maximal activation (pCa(50)) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity (V(o)) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, P(o), F(max) per CSA (P > 0.05), and pCa(50) were increased and V(o) decreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ~2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, P(o), F(max) per CSA, V(o), and pCa(50) were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca(2+) sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.     

Resistance exercise as a countermeasure to disuse-induced bone loss.

During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly (P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. -1%; total hip BMD, +1% vs. -3%; calcaneus BMD, +1% vs. -9%; pelvis BMD, -0.5% vs. -3%; total body BMD, 0% vs. -1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. -15%; parathyroid hormone intact molecule, +18% vs. -25%; and serum and ionized calcium, -1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. -199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight.     

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.     

Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest

This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.     

Human soleus single muscle fiber function with exercise or nutrition countermeasures during 60 days of bed rest

The soleus muscle has been consistently shown to atrophy more than other leg muscles during unloading and is difficult to protect using various exercise countermeasure paradigms. However, the efficacy of aerobic exercise, a known stimulus for oxidative adaptations, has not been tested in combination with resistance exercise (RE), a known hypertrophic stimulus. We hypothesized that a concurrent exercise program (AE + RE) would preserve soleus fiber myosin heavy chain (MHC) I size and function during 60 days of bed rest. A secondary objective was to test the hypothesis that a leucine-enriched high protein diet would partially protect soleus single fiber characteristics. Soleus muscle biopsies were obtained before and after bed rest from a control (BR; n = 7), nutrition (BRN; n = 8), and exercise (BRE; n = 6) group. Single muscle fiber diameter (Dia), peak force (Po), contractile velocity, and power were studied. BR decreased (P < 0.05) MHC I Dia (-14%), Po (-38%), and power (-39%) with no change in contractile velocity. Changes in MHC I size (-13%) and contractile function (approximately 30%) from BRN were similar to BR. BRE decreased (P < 0.05) MHC I Dia (-13%) and Po (-23%), while contractile velocity increased (P < 0.05) 26% and maintained power. These soleus muscle data show 1) the AE + RE exercise program maintained MHC I power but not size and strength, and 2) the nutrition countermeasure did not benefit single fiber size and contractile function. The divergent response in size and functional MHC I soleus properties with the concurrent exercise program was a unique finding further highlighting the challenges of protecting the unloaded soleus.     

High-density surface EMG study on the time course of central nervous and peripheral neuromuscular changes during 8 weeks of bed rest with or without resistive vibration exercise

The aim of the present study was to assess the time course and the origin of adaptations in neuromuscular function as a consequence of prolonged bed rest with or without countermeasure. Twenty healthy males volunteered to participate in the present study and were randomly assigned to either an inactive control group (Ctrl) or to a resistive vibration exercise (RVE) group. Prior to, and seven times during bed rest, we recorded high-density surface electromyogram (sEMG) signals from the vastus lateralis muscle during isometric knee extension exercise at a range of contraction intensities (5–100% of maximal voluntary isometric torque). The high-density sEMG signals were analyzed for amplitude (root mean square, RMS), frequency content (median frequency, F_med) and muscle fiber conduction velocity (MFCV) in an attempt to describe bed rest-induced changes in neural activation properties at the levels of the motor control and muscle fibers. Without countermeasures, bed rest resulted in a significant progressive decline in maximal isometric knee extension strength, whereas RMS remained unaltered throughout the bed rest period. In line with observed muscle atrophy, both F_med and MFCV declined during bed rest. RVE training during bed rest resulted in maintained maximal isometric knee extension strength, and a strong increase (～30%) in maximal EMG amplitude, from 10 days of bed rest on. Exclusion of other factors led to the conclusion that the RVE training increased motor unit firing rates as a consequence of an increased excitability of motor neurons. An increased firing rate might have been essential under training sessions, but it did not affect isometric voluntary torque capacity.     

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.     

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.     

Effects of acute moderate-intensity exercise on carnitine metabolism in men and women

The purpose of this investigation was to describe the dynamics of carnitine metabolism during an acute episode of exercise. Twenty-eight subjects (14 male; 14 female) exercised for 40 min on a bicycle ergometer at 55% of their maximal aerobic capacities. Blood samples were obtained at rest, 10, 20, 30, and 40 min of exercise, and 15-min postexercise. Muscle biopsies of the vastus lateralis were performed before and after exercise. Results demonstrated that the percent of acylated plasma carnitine increased significantly (P less than 0.05) across all subjects from 17.3% at rest to 22.3% by 40 min of exercise and continued to increase to 22.8% 15-min postexercise. Total muscle carnitine levels fell significantly (P less than 0.001) across all subjects from 4.21 (1.27) (means +/- SD) mumol/g wet weight at rest to 3.29 (1.27) mumol/g wet weight after exercise. Well-trained males and females had almost identical levels of muscle carnitine [4.35(1.86) and 4.34 (0.64) mumol/g wet weight, respectively]. These levels were somewhat higher but not significantly higher than their moderately trained counterparts [3.86(1.34) and 4.28(1.18) males and females, respectively]. Carnitine palmitoyl transferase (E.C. 2.3.1.21) activity also declined significantly (P less than 0.05) across all subjects after exercise. This study is the first to demonstrate a potential loss of acylated carnitine forms from muscle to plasma during acute exercise, possibly reflecting an increase in carnitine turnover. Alterations in carnitine status may represent another metabolic adaptation to chronic exercise training.     

Cardiac atrophy after bed rest and spaceflight.

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.     

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.     

Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures.

While microgravity exposure is known to cause deterioration of skeletal muscle performance, little is known regarding its effect on tendon structure and function. Hence, the aims of this study were to investigate the effects of simulated microgravity on the mechanical properties of human tendon and to assess the effectiveness of resistive countermeasures in preventing any detrimental effects. Eighteen men (aged 25-45 yr) underwent 90 days of bed rest: nine performed resistive exercise during this period (BREx group), and nine underwent bed rest only (BR group). Calf-raise and leg-press exercises were performed every third day using a gravity-independent flywheel device. Isometric plantar flexion contractions were performed by using a custom-built dynamometer, and ultrasound imaging was used to determine the tensile deformation of the gastrocnemius tendon during contraction. In the BR group, tendon stiffness estimated from the gradient of the tendon force-deformation relation decreased by 58% (preintervention: 124 +/- 67 N/mm; postintervention: 52 +/- 28 N/mm; P < 0.01), and the tendon Young's modulus decreased by 57% postintervention (P < 0.01). In the BREx group, tendon stiffness decreased by 37% (preintervention: 136 +/- 66 N/mm; postintervention: 86 +/- 47 N/mm; P < 0.01), and the tendon Young's modulus decreased by 38% postintervention (P < 0.01). The relative decline in tendon stiffness and Young's modulus was significantly (P < 0.01) greater in the BR group compared with the BREx group. Unloading decreased gastrocnemius tendon stiffness due to a change in tendon material properties, and, although the exercise countermeasures did attenuate these effects, they did not completely prevent them. It is suggested that the total loading volume was not sufficient to completely prevent alterations in tendon mechanical properties.     

Effect of exercise intensity on mild rhythmic-handgrip-exercise-induced functional sympatholysis

This study attempts to clarify whether intensity of exercise influences functional sympatholysis during mild rhythmic handgrip exercise (RHG). We measured muscle oxygenation in both exercising and non-exercising muscle in the same arm in 11 subjects using near infrared spectroscopy (NIRS), heart rate, and blood pressure. We used the total labile signal to assess the relative muscle oxygenation by occlusion for 6 min. Subjects performed RHG (20 times/min) for 6 min at 10%, 20%, and 30% of maximal voluntary contraction (MVC) at random. We used a non-hypotensive lower body negative pressure (LBNP) of 220 mmHg for 2 min to elicit reproducible enhancement in muscle sympathetic nerve activity (MSNA) at rest and during RHG. LBNP caused decreases of 16.4% and 17.7% of the level of muscle oxygenation at rest (pre) in exercising (forearm) and non-exercising (upper arm) muscle respectively. Muscle oxygenation in non-exercising muscle with the application of LBNP during RHG did not change significantly at each intensity. In contrast, the decrease in muscle oxygenation in exercising muscle attenuated progressively as exercise intensity increased (10% MVC 8.8+/-2.8%, 20% MVC 7.1+/-2.0%, 30% MVC 4.6+/-3.0%), when LBNP was applied during RHG. The attenuation of the decrease in muscle oxygenation due to LBNP during RHG at 10%, 20%, and 30% was significantly different from that at rest (p<0.01). These findings indicate that functional sympatholysis during mild RHG might be attributed to exercise intensity.