Artificial gravity with ergometric exercise can prevent enhancement of popliteal vein compliance due to 4-day head-down bed rest

Changes of venous compliance may contribute in part to postflight orthostatic intolerance. The purpose of the present study was to determine whether intermittent artificial gravity exposure with ergometric exercise could prevent venous compliance changes in the lower limbs due to simulated weightlessness. Twelve healthy male volunteers were exposed to simulated microgravity for 4 days of head-down bed rest (HDBR). Six subjects were randomly loaded 1.0–2.0 Gz intermittent artificial gravity (at foot level) with 40 W of ergometric workload every day (countermeasure group, CM). The six others served as the control (CON group). Venous compliance was estimated by measuring the corresponding change of cross-sectional area (CSA) of popliteal vein at each minute of various venous occlusion pressure stages. Basal CSA was significantly lower after bed rest in the control group, and preserved in the countermeasure group. The percent increase in the CSA of CON group was significantly greater almost at each minute of various venous cuff pressures after bed rest than before. Compliance of popliteal vein of CON group was significant greater when 40, 60 and 80 mmHg cuff pressure applied after bed rest than before of CON group. In conclusions, a 4-day simulated weightlessness leads to increase of popliteal venous compliance; centrifuge-induced artificial gravity with ergometric exercise can prevent enhancement of popliteal venous compliance due to 4-day head-down tilt bed rest, the effect of the countermeasure on compliance might involve changes in venous filling and changes in venous structure.     

Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters

Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20–45 years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD⁺ subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise.     

Characteristics of fast voluntary and electrically evoked isometric knee extensions during 56 days of bed rest with and without exercise countermeasure

The contractile characteristics of fast voluntary and electrically evoked unilateral isometric knee extensions were followed in 16 healthy men during 56 days of horizontal bed rest and assessed at bed rest days 4, 7, 10, 17, 24, 38 and 56. Subjects were randomized to either an inactive control group (Ctrl, n = 8) or a resistive vibration exercise countermeasure group (RVE, n = 8). No changes were observed in neural activation, indicated by the amplitude of the surface electromyogram, or the initial rate of voluntary torque development in either group during bed rest. In contrast, for Ctrl, the force oscillation amplitude at 10 Hz stimulation increased by 48% (P < 0.01), the time to reach peak torque at 300 Hz stimulation decreased by 7% (P < 0.01), and the half relaxation time at 150 Hz stimulation tended to be slightly reduced by 3% (P = 0.056) after 56 days of bed rest. No changes were observed for RVE. Torque production at 10 Hz stimulation relative to maximal (150 Hz) stimulation was increased after bed rest for both Ctrl (15%; P < 0.05) and RVE (41%; P < 0.05). In conclusion, bed rest without exercise countermeasure resulted in intrinsic speed properties of a faster knee extensor group, which may have partly contributed to the preserved ability to perform fast voluntary contractions. The changes in intrinsic contractile properties were prevented by resistive vibration exercise, and voluntary motor performance remained unaltered for RVE subjects as well.     

A pilot evaluation of a neuromuscular electrical stimulation (NMES) based methodology for the prevention of venous stasis during bed rest

Bed rest poses an increased risk factor for a potentially fatal venous thromboembolism (VTE). Lack of activation of the calf muscle pump during this resting period gives rise to venous stasis which may lead to deep vein thrombosis (DVT) development. Our aim was to investigate the effects that 4 h of bed rest have on the lower limb hemodynamics of healthy subjects and to what extent electrically elicited contractions of the calf muscles can alleviate these effects. Outcome variables included popliteal vein blood flow and heart rate. Primary results indicated that the resting group experienced a significant decline in popliteal venous blood flow of ～47% with ～13% decrease in heart rate. The stimulated groups maintained a significantly higher venous blood flow and heart rate. Volume flow in the contralateral limb remained constant throughout the study and was comparable to that of the stimulated limb's recovery flow. The results suggest that even short periods of bed rest can significantly reduce lower limb blood flow which could have implications for DVT development. Electrically elicited calf muscle contractions significantly improve lower limb blood flow and can alleviate some debilitating effects of bed rest.     

Artificial gravity with ergometric exercise as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans

We have shown previously that combined short-arm centrifuge and aerobic exercise training preserved several physiologically important cardiovascular functions in humans. We hypothesized that artificial gravity (AG) and exercise is effective to prevent changes of physical problems during head-down bed rest (HDBR). To test this hypothesis, 12 healthy male subjects had undergone 4 days of 6° HDBR. Six of them were exposed to AG of an alternating 2-min intervals of +1.0 and +2.0 Gz at foot level for 30 min twice per day with ergometric exercise of 40 W as a countermeasure during bed rest (CM group), while the remaining six served as untreated controls (no-CM group). Before and after 4 days of bed rest, leg venous hemodynamics was assessed by venous occlusion plethysmography and autonomic cardiovascular control estimated by power spectral analysis of blood pressure and heart rate. Further, orthostatic tolerance was evaluated by a 75° head-up tilt test and physical working capacity was surveyed by near maximal physical working capacity test before and after bed rest. The data showed that combined centrifuge and exercise applied twice daily for a total of 60 min during 4 days of HDBR prevented (a) a decrease in working capacity, (b) autonomic dysfunction (a decrease in the activity of parasympathetic cardiac innervation) and (c) an increase in leg venous flow resistance. The combination of a 30 min alternating of +1.0 and +2.0 Gz for twice per day of AG with 40 W ergometric exercise may offer a promising countermeasure to short duration simulated microgravity.     

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head‐down bed rest

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head‐down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio‐cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head‐down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head‐down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: ?201 ± 37 mL vs. control: ?345 ± 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head‐down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head‐down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.     

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest

Orthostatic intolerance (OI) is the most serious symptom of cardiovascular deconditioning induced by head-down bed rest or weightlessness. Wearing venoconstrictive thigh cuffs is an empirical countermeasure used by Russian cosmonauts to limit the shift of fluid from the lower part of the body to the cardio-cephalic region. Our aim was to determine whether or not thigh cuffs help to prevent orthostatic hypotension induced by head-down bed rest. We studied the effect of thigh cuffs on eight healthy men. The cuffs were worn during the day for 7 days of head-down bed rest. We measured: orthostatic tolerance (stand tests and lower body negative pressure tests), plasma volume (Evans blue dilution), autonomic influences (plasma noradrenaline) and baroreflex sensitivity (spontaneous baroreflex slope). Thigh cuffs limited the loss of plasma volume (thigh cuffs: -201 +/- 37 mL vs. control: -345 +/- 42 mL, P < 0.05), the degree of tachycardia and reduction in the spontaneous baroreflex sensitivity induced by head-down bed rest. However, the impact of thigh cuffs was not sufficient to prevent OI (thigh cuffs: 7.0 min of standing time vs. control: 7.1 min). Decrease in absolute plasma volume and in baroreflex sensitivity are known to be important factors in the aetiology of OI induced by head-down bed rest. However, dealing with these factors, using thigh cuffs for example, is not sufficient to prevent OI. Other factors such as venous compliance, microcirculatory changes, peripheral arterial vasoconstriction and vestibular afferents must also be considered.     

Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans

We investigated the alteration in flow-dependent-dilatation in the orthostatic intolerance occurring after bed-rest deconditioning. Eight men [aged mean (SEM) 32 (2) years] underwent two consecutive periods of 7 days of head-down-tilt (HDT, –6°) during bed rest. A control age and sex matched group [n=8, 30 (2) years], maintained its usual physical activity. Blood flow velocity (BFV) and diameter (Doppler and echotracking systems) were measured in the brachial artery, under basal conditions and during the post ischaemic hyperaemia following occlusion. The increase in BFV post-ischaemia did not change before, during and after HDT but the relative increase in the diameter was greater on the 7th day of the HDT period than before HDT [+8.8 (1.6)% compared to +3.7 (1.0)%, P<0.001]. After HDT, 11 of 16 standing tests (comprising eight subjects in the two HDT periods) had to be stopped because of orthostatic intolerance. The flow-dependent-dilatation measured at the end of HDT was negatively correlated with the post-bed-rest duration of orthostatic tolerance (r=0.78, P<0.01). After the sublingual administration of glyceryl trinitrate, there was no change in the increase in diameter. No significant changes were observed in the control group. Bed-rest deconditioning enhances the flow-dependent vasodilatation of large arteries and might contribute to the orthostatic intolerance observed following bed-rest. Electronic Publication     

Hemodynamic effects of habituation to a week-long program of neuromuscular electrical stimulation

ObjectivesNeuromuscular electrical stimulation (NMES) of the calf muscles has been shown to cause instantaneous increases in venous outflow from the lower leg and could be used as an adjunct to current gold-standard compression therapies for the prevention of venous stasis and its related pathologies. However, little is known about the effects of NMES in combination with compression therapies on subject comfort, compliance and popliteal venous blood flow over the course of a week-long NMES protocol. This study aimed to assess the effects of a NMES and compression protocol for the prevention of venous stasis on the compliance, comfort and venous blood flow of healthy volunteers over the course of seven days.DesignTwenty-four healthy subjects were assigned to either a stimulation or control group. The stimulation group received 1.5 h of NMES daily while the control group received none. Daily measures of popliteal venous blood flow, subject compliance and comfort were recorded over 7 days.ResultsEjected blood flow volumes and peak velocities in the popliteal vein during NMES were sustained over a 30-min stimulation session and increased by approximately 100% over the course of seven days. Mean stimulation intensities increased progressively throughout the week, while perceived pain during NMES decreased significantly. Mean compliance to the 7-day protocol was 100%.ConclusionUser habituation to a combined NMES and compression protocol resulted in significant increases in ejected venous volume and peak velocity over the course of 7 days. This resulted in the highest ejected venous volume reported from a single NMES induced contraction of the calf muscles to date which was twice the magnitude of values previously reported in the literature. These findings suggest that NMES based protocols applied over an extended period of days, weeks or months may provide greater hemodynamic effect for the prevention of venous stasis than previously observed during NMES sessions lasting less than a few hours.     

Human skeletal muscle structure and function preserved by vibration muscle exercise following 55 days of bed rest

Prolonged immobilization of the human body results in functional impairments and musculoskeletal system deconditioning that may be attenuated by adequate muscle exercise. In a 56-day horizontal bed rest campaign involving voluntary males we investigated the effects of vibration muscle exercise (RVE, 2×6 min daily) on the lower limb skeletal muscles using a newly designed foot plantar trainer (Galileo Space) for use at supine position during bed rest. The maximally voluntary isometric plantar flexion force was maintained following regular RVE bouts during bed rest (controls −18.6 %, P<0.05). At the start (BR2) and end of bed rest (BR55) muscle biopsies were taken from both mixed fast/slow-type vastus lateralis (VL) and mainly slow-type soleus muscle (SOL), each having n=10. RVE group: the size of myofiber types I and II was largely unchanged in VL, and increased in SOL. Ctrl group: the SOL depicted a disrupted pattern of myofibers I/II profiles (i.e., type II>140 % vs. preBR) suggesting a slow-to-fast muscle phenotype shift. In RVE-trained SOL, however, an overall conserved myofiber I/II pattern was documented. RVE training increased the activity-dependent expression of nitric oxide synthase type 1 immunofluorescence at SOL and VL myofiber membranes. These data provide evidence for the beneficial effects of RVE training on the deconditioned structure and function of the lower limb skeletal muscle. Daily short RVE should be employed as an effective atrophy countermeasure co-protocol preferentially addressing postural calf muscles during prolonged clinical immobilization or long-term human space missions.     

Are energy metabolism alterations involved in cardiovascular deconditioning after weightlessness? An hypothesis

The physiopathogenesis of the cardiovascular deconditioning syndrome observed after actual and simulated microgravity is still under debate, despite numerous studies conducted on the role of blood volume, hormones involved in its regulation, sympathetic nervous system, baroreflexes and venous compliance. Orthostatic intolerance, a reduced exercise capacity and an increased heart rate at rest characterize this syndrome. Recent data suggest, first, the presence of a complex loop between the sympathetic nervous system, carbohydrate metabolism (insulin) and leptin hormone and, second, that this loop, an overall reflection of energy metabolism, participates in cardiovascular regulation. After a resume of studies conducted on fuel homeostasis during actual and simulated microgravity, the possible implications of energy metabolism in the development of the cardiovascular deconditioning syndrome will be discussed.     

A comparison of blood gases and acid-base measurements in arterial,arterialized venous,and venous blood during short-term maximal exercise

Summary The purpose of this study was to determine the relationship between blood gases and acid-base measurements in arterial, arterialized venous, and venous blood measured simultaneously during short-term maximal exercise. Ten well-trained male cyclists performed a graded maximal exercise test on a cycle ergometer to determine the power output corresponding to their peak oxygen consumption (test I), and a short-term maximal test on a cycle ergometer at peak power output (test 11). During test 11 arterial, arterialized venous and venous blood were sampled simultaneously for determination of partial pressures of oxygen and carbon dioxide, pH, bicarbonate (HCO₃ ^–), base excess (BE), and lactate (La). Samples were taken at rest, the end of 1 min of exercise (1 ME), at the end of exercise (EE), and at 2 min of recovery (REC). During test II, subjects maintained a peak power output of 370.6 (62.1) W [mean (SD)] for 4.5, SD 1.6 min. Except at rest venous and arterialized venous measurements tended to be the same at all sampling intervals, but differed significantly from measurements in arterial blood (P<0.05). BE was the only variable that rendered consistently significant correlations between arterial and arterialized venous blood at each sampling interval. The pooled correlation coefficient between arterial and arterialized venous BE was r=0.83 [regression equation: BE_a=(0.84 BE_av)–0.51]. Arterial La was significantly higher than venous La at 1 ME (2.8, 0.7 vs 0.8, 0.3mmol · 1^–1) and higher than both venous and arterialized venous La at EE. At EE La concentration was 9.2, SD 2.0, 4.6, SD 0.4, and 5.1, SD 0.1 mmol · 1^–1 in arterial, venous, and arterialized venous blood respectively. It is concluded that except for base excess, blood gases and acid base measurements in venous and arterialized venous blood do not accurately reflect values found in arterial blood during short-term maximal exercise. We suggest that these differences may be due in part to clearance by inactive muscle near the sampling site or vasoconstriction at the inactive sampling site.     

Continuous measurement of venous diameter by a combined photoelectric-photographic and plethysmographic technique

Summary The combined photoelectric-photographic and plethysmographic technique allows for the investigation of the distensibility characteristics and pharmacological influence on the capacitance vessels in an uniform vascular bed (skin veins of the isolated rabbit ear). Diameter changes of a vein segment are recorded continuously by means of a photoresistor and are photographed for calibration. Volume changes of the tissue are measured by a water filled plethysmograph and can be compared with diameter changes of the selected vein segment. The method allows for better interpretation of the results obtained by the plethysmographic technique. In particular, it is possible to distinguish between outward filtration and stress-relaxation.This research was supported by Contract, F 44620-71-C-0117 of the USAF School of Aerospace Medicine, European Office of Aerospace Research (OAR) United States Air Force and Deutsche Forschungsgemeinschaft     

Short-term unilateral leg immobilization alters peripheral but not central arterial structure and function in healthy young humans

Short-term leg immobilization is an acute model of inactivity, which induces vascular deconditioning. The present study was conducted to determine if short-term leg immobilization induced alterations in central and peripheral conduit artery structure (diameter and compliance), function (resting blood flow and mean wall shear rate), and peripheral flow-mediated dilation. Healthy participants (n?=?7 women and n?=?8 men) were studied before and after 12?days of unilateral leg immobilization. Carotid artery structure and function were unaltered with immobilization indicating that the unilateral immobilization did not have a detectable effect on this representative central artery. In contrast, peripheral measures of arterial structure at the common femoral and popliteal arteries showed significant reductions in both the immobilized and non-immobilized limbs but to a greater extent in the immobilized limbs. Specifically, femoral and popliteal artery compliance and femoral artery diameter were reduced in both the immobilized and the non-immobilized limb (p?<?0.05) while popliteal artery diameter was reduced only in the immobilized leg. Popliteal artery flow-mediated dilation, an indicator of peripheral artery function, was increased in the immobilized limb, which parallels reports in paralyzed limbs of spinal-cord-injured individuals. The time course of vascular alterations with inactivity likely follows a sequence of adaptations in arterial structure and function reflecting differing initial flow patterns, and arterial wall composition, and diverse hemodynamic stimuli within different blood vessels.     

Effects of vibration training on bone metabolism: results from a short-term bed rest study

The absence of mechanical loading leads to a prompt increase in bone resorption measured by bone resorption markers. There is high potential that vibration training can positively influence bone metabolism in immobilized subjects, reduce the increase in osteoclastic activity and increase bone formation processes. We investigated whether vibration training at 20 Hz with an amplitude of 2–4 mm influences bone metabolism during immobilization. Eight male subjects (26.4 ± 4.9 years; 78.1 ± 9.5 kg) performed a 14 day bed rest in 6°-head down tilt (HDT). Subjects received vibration training for 2 × 5 min/day or a control intervention without vibration (crossover design). Calcium excretion and bone resorption markers C-telopeptide (CTX) and N-telopeptide (NTX) were analyzed from 24 h urine samples. Bone formation markers, bone alkaline phosphatase (bAP) and procollagen-N propeptide (PINP) were analyzed from fasting blood samples. Our results show an increase in bone resorption very early during HDT bed rest in both interventions (CTX: p < 0.01; NTX: p < 0.001). Vibration training did not have any different effect on bone resorption markers (CTX: p = 0.10; NTX: p = 0.58), bone formation markers (PINP: p = 0.21; bAP: p = 0.12) and calcium excretion (p < 0.64) compared to the control condition. Mere vibration training with 20 Hz for 2 × 5 min/day does not prevent increase in bone resorption as measured with the described methods in our short-term HDT bed rest.     

Use of continuous glucose monitoring in normoglycemic, insulin-resistant women

The purpose of this study was to compare fasting and post-prandial glucose concentrations measured in venous blood with continuous glucose monitoring (CGM)-derived values, with and without prior exercise, in insulin-resistant, normoglycemic women. Interstitial and venous glucose concentrations were assessed in ten sedentary, overweight/obese African-American women following a sedentary condition (75 min of rest) and following an exercise condition (75 min of brisk walking on a treadmill). Ninety minutes after rest or exercise, participants completed an oral glucose tolerance test (OGTT). In response to the OGTT, CGM-derived glucose area under the curves (AUC) were lower than venous values in the exercise condition (−25%, p = 0.03) but this difference was attenuated in the sedentary condition (−10%, p = 0.09). Additionally, CGM-derived absolute glucose values (mMol) were significantly lower compared to venous values during the sedentary (p = 0.007) and exercise conditions (p = 0.006). Overall, there was a moderately strong relationship between venous and CGM-derived glucose AUC (r ² = 0.68) but the CGM-derived values were consistently lower in this study group. Although CGM provided more information regarding post-prandial glucose responses, these results suggest that CGM may not closely match venous glucose measurements in normoglycemic participants.     

Hemodynamic responses to simulated weightlessness of 24-h head-down bed rest and KAATSU blood flow restriction

The KAATSU training is a unique method of muscle training with restricting venous blood flow, which might be applied to prevent muscle atrophy during space flight, but the effects of KAATSU in microgravity remain unknown. We investigated the hemodynamic responses to KAATSU during actually simulated weightlessness (6° head-down tilt for 24 h, n = 8), and compared those to KAATSU in the seated position before bed rest. KAATSU was applied to the proximal ends of both the thighs. In the seated position before bed rest, sequential incrementing of KAATSU cuff pressure and altering the level of blood flow restriction resulted in a decrease in stroke volume (SV) with an increase in heart rate (HR). KAATSU (150–200 mmHg) decreased SV comparable to standing. Following 24-h bed rest, body mass, blood volume (BV), plasma volume (PV), and diameter of the inferior vena cava (IVC) were significantly reduced. Norepinephrine (NOR), vasopressin (ADH), and plasma renin activity (PRA) tend to be reduced. A decrease in SV and CO induced by KAATSU during the simulated weightlessness was larger than that in the seated position before bed rest, and one of eight subjects developed presyncope due to hypotension during 100 mmHg KAATSU. High-frequency power (HF_RR) decreased during KAATSU and standing, while low-frequency/high-frequency power (LF_RR/HF_RR) increased significantly. NOR, ADH and PRA also increased during KAATSU. These results indicate that KAATSU blood flow restriction reproduces the effects of standing on HR, SV, NOR, ADH, PRA, etc., thus stimulating a gravity-like stress during simulated weightlessness. However, syncope due to lower extremity blood pooling and subsequent reduction of venous return may be induced during KAATSU in microgravity as reported in cases of lower-body negative pressure.     

Strength, size and activation of knee extensors followed during 8 weeks of horizontal bed rest and the influence of a countermeasure

Changes in the quadriceps femoris muscle with respect to anatomical cross sectional area (CSA), neural activation level and muscle strength were determined in 18 healthy men subjected to 8 weeks of horizontal bed rest (BR) with (n = 9) and without (n = 9) resistive vibration exercise (RVE). CSA of the knee extensor muscle group was measured with magnetic resonance imaging every 2 weeks during bed rest. In the control subjects (Ctrl), quadriceps femoris CSA decreased linearly over the 8 weeks of bed rest to −14.1 ± 5.2% (P < 0.05). This reduction was significantly (P < 0.001) mitigated by the exercise paradigm (−3.5 ± 4.2%; P < 0.05). Prior to and seven times during bed rest, maximal unilateral voluntary torque (MVT) values of the right leg were measured together with neural activation levels by means of a superimposed stimulation technique. For Ctrl, MVT decreased also linearly over time to −16.8 ± 7.4% after 8 weeks of bed rest (P < 0.01), whereas the exercise paradigm fully maintained MVT during bed rest. In contrast to previous reports, the maximal voluntary activation remained unaltered for both groups throughout the study. For Ctrl, the absence of deterioration of the activation level might have been related to the repeated testing of muscle function during the bed rest. This notion was supported by the observation that for a subset of Ctrl subjects (n = 5) the MVT of the left leg, which was not tested during BR, was reduced by 20.5 ± 10.1%, (P < 0.01) which was for those five subjects significantly (P < 0.05) more than the 11.1 ± 9.2% (P < 0.01) reduction for the right, regularly tested leg.Grants The BBR study was supported by grant 14431/02/NL/SH2 from the European Space Agency. The study was further sponsored by Charité—University Medicine Berlin (Campus Benjamin Franklin), DLR (German AeroSpace), MSD Sharp & Dohme, Lilly Germany, Servier Germany, Hoffmann-LaRoche, Siemens, Novartis, and Seca.