Effects of long-term head-down-tilt bed rest and different training regimes on the coagulation system of healthy men

Immobility plus preexisting chronic disease or acute trauma can activate the coagulation system, thus increasing the risk for thromboembolic events. The effects of long-term bed-rest immobility and microgravity on the coagulation system of healthy persons (e.g., during crewed Mars missions) have not yet been studied. The main objective of the second Berlin BedRest Study (BBR2-2) "Coagulation Part" was to investigate adaptations of the hemostatic system during long-term bed rest (60 days) under simulated microgravity (6° head-down-tilt [6°HDT]) and after mobilization in three different volunteer groups (randomly assigned to CTR= inactive control group; RE= resistive exercise only group; and RVE= resistive exercise with whole-body vibration group). In 24 males (aged 21-45 years), before, during, and after long-term bed rest, key parameters of coagulation were measured from venous blood samples: D-dimer (DD), thrombin-antithrombin III complex (TAT), and prothrombin fragment F1 + 2 (PT-F1 + 2). Additionally, modified rotational thrombelastometry (ROTEM (®) ) analysis was performed. Times of exploratory analyses were as follows: baseline data collection 2 days before bed rest (BDC-2); eight different days of 6°HDT bed rest (HDT1-HDT60), and two different days after reambulation (R + 3 and R + 6). We found significant changes in DD, TAT, and PT-F1 + 2 over the total time course, but no consistent effect of physical interventions (RE, RVE) on these parameters. Notably, no parameter reached levels indicative of intravascular thrombin formation. All ROTEM® parameters remained within the normal range and no pathological traces were found. Sixty days of 6°HDT bed rest are not associated with pronounced activation of the coagulation system indicative of intravascular thrombus formation in healthy volunteers independent of the training type during the bed rest.

Resistive exercises, with or without whole body vibration, prevent vertebral marrow fat accumulation during 60 days of head-down tilt bed rest in men

Fat accumulates in the bone marrow of lumbar vertebrae with bed rest. Exercise with or without whole body vibration may counter this effect. Our objectives were to measure 1) the vertebral fat fraction (VFF) of men subjected to bed rest who performed resistive exercises with (RVE, n = 7) or without whole body vibration(RE, n = 8) or no exercise (CTR, n = 9) using three MRI techniques; and 2) changes in peripheral blood counts. Twenty-four healthy men (age: 20-45 yr) underwent -6° head-down tilt (HDT) bed rest for 60 days. MRI was performed using three techniques (fat saturation, proton spectroscopy, and in and out of phase) to measure the fat fraction of L(3), L(4), and/or L(5) at baseline, mid-HDT, and end-HDT. Erythrocytes and leukocytes were counted at HDT days 19, 33, 47, 54, and 60. The mean absolute VFF was increased in the CTR group at mid-HDT and end-HDT (+3.9 ± 1.3 and +3.6 ± 1.2%, respectively, both P < 0.05). The RE group had a smaller VFF change than the CTR group at mid-HDT (-0.9 ± 1.2 vs. +3.9 ± 1.3%, P < 0.05). The RVE group had a smaller VFF change than the CTR group at end-HDT (-2.6 ± 1.9 vs. +3.5 ± 1.2%, P < 0.05). Erythrocyte counts were increased in all groups at HDT day 19 and HDT day 33 and in the RE group at HDT day 54 (all P < 0.05). Bed rest for 60 days at -6° HDT increased lumbar VFF in men beyond natural involution. RVE and RE regimens effectively prevented VFF accumulation. Higher erythrocyte counts were not altered by RVE or RE. Whole body vibration, along with RE administered to people with prolonged immobility, may prevent fat accumulation in their bone marrow.

Muscle atrophy, pain, and damage in bed rest reduced by resistive (vibration) exercise

The purpose of this study was to investigate the effectiveness of a short-duration (5-6 min, 3 d·wk) resistive exercise program with (RVE) or without (RE) whole-body vibration in reducing muscle atrophy in the lower limb during prolonged inactivity when compared with that in an inactive control group. METHODS: As part of the second Berlin BedRest Study, 24 male subjects underwent 60 d of head-down tilt bed rest. Using magnetic resonance imaging, muscle volumes of the individual muscles of the lower limb were calculated before and at various intervals during and after bed rest. Pain levels and markers of muscle damage were also evaluated during and after bed rest. Adjustment of P values to guard against false positives was performed via the false discovery rate method. RESULTS: On the "intent-to-treat" analysis, RE reduced atrophy of the medial and lateral gastrocnemius, soleus, vasti, tibialis posterior, flexor hallucis longus, and flexor digitorum longus (P ≤ 0.045 vs control group) and RVE reduced atrophy of the medial and lateral gastrocnemius and tibialis posterior (P ≤ 0.044). Pain intensity reports after bed rest were lower in RE at the foot (P ≤ 0.033) and whole lower limb (P = 0.01) and in RVE at the thigh (P ≤ 0.041), lower leg (P ≤ 0.01), and whole lower limb (P ≤ 0.036). Increases in sarcomere-specific creatine kinase after bed rest were less in RE (P = 0.020) and RVE (P = 0.020). No differences between RE and RVE were observed. CONCLUSIONS: In conclusion, a short-duration RVE or RE can be effective in reducing the effect of prolonged bed rest on lower extremity muscle volume loss during bed rest and muscle damage and pain after bed rest. Copyright © 2014 by the American College of Sports Medicine.

Differential atrophy of the lower-limb musculature during prolonged bed-rest

Patients with medical, orthopaedic and surgical conditions are often assigned to bed-rest and/or immobilised in orthopaedic devices. Although such conditions lead to muscle atrophy, no studies have yet considered differential atrophy of the lower-limb musculature during inactivity to enable the development of rehabilitative exercise programmes. Bed-rest is a model used to simulate the effects of spaceflight and physical inactivity. Ten male subjects underwent 56-days of bed-rest. Magnetic resonance imaging of the lower-limbs was performed at 2-weekly intervals during bed-rest. Volume of individual muscles of the lower-limb and subsequently, rates of atrophy were calculated. Rates of atrophy differed (F = 7.4, p < 0.0001) between the muscles with the greatest rates of atrophy seen in the medial gastrocnemius, soleus and vastii (p < 0.00000002). The hamstring muscles were also affected (p < 0.00015). Atrophy was less in the ankle dorsiflexors and anteromedial hip muscles (p > 0.081). Differential rates of atrophy were seen in synergistic muscles (e.g. adductor magnus > adductor longus, p = 0.009; medial gastrocnemius > lateral gastrocnemius, p = 0.002; vastii > rectus femoris, p = 0.0002). These results demonstrate that muscle imbalances can occur after extended periods of reduced postural muscle activity, potentially hampering recovery on return to full upright body position. Such deconditioned patients should be prescribed "closed-chain" simulated resistance exercises, which target the lower-limb antigravity extensor muscles which were most affected in bed-rest.

The double sensor-a non-invasive device to continuously monitor core temperature in humans on earth and in space

The objective of our study was to establish whether rectal temperature recordings in humans could be replaced by a non-invasive skin temperature sensor combined with a heat flux sensor (Double Sensor) located at the forehead to monitor core body temperature changes due to circadian rhythms. Rectal and Double Sensor data were collected continuously for 24h in seven men undertaking strict head-down tilt bed-rest. Individual differences between the two techniques varied between -0.72 and +0.55 degrees C. Nonetheless, when temperature data were approximated by cosinor analysis in order to compare circadian rhythm profiles between methods, it was observed that there were no significant differences between mesor, amplitude, and acrophase (P>0.310). It was therefore concluded that the Double Sensor technology is presently not accurate enough for performing single individual core body temperature measurements under resting conditions at normal ambient room temperature. Yet, it seems to be a valid, non-invasive alternative for monitoring circadian rhythm profiles.

Decision making after 50 days of simulated weightlessness

By restricting physical activity levels, the bed rest simulation of weightlessness could be associated with changes in prefrontal cortex functioning that manifest as cognitive decrements, particularly for executive cognitive functions. We aimed to determine if performance on an executive function task was indeed affected by bed rest. The Iowa Gambling Task, a card game measuring real-life decision making processes, was administered to 25 healthy males (aged 21-45 years) selected to undergo 60 days of 6 degrees head-down tilt bed rest for the 2nd Berlin BedRest Study (BBR2-2). Testing was conducted either 6 days before beginning bed rest (n=13) or on the 51st day of bed rest (n=12). The task performance scores of subjects tested before bed rest were not significantly different from those tested during bed rest. However, subjects tested during bed rest failed to adapt their card selection strategy as the Iowa Gambling Task progressed. This was unlike the subjects tested before bed rest, who switched between decks on consecutive card selections less frequently in latter stages of the task. An influence of prolonged bed rest on decision making could have implications for the planning of human spaceflights to Mars, or for any circumstance in which adequate physical activity levels are not achieved.

Countermeasures against lumbar spine deconditioning in prolonged bed rest: resistive exercise with and without whole body vibration

To evaluate the effect of short-duration, high-load resistive exercise, with and without whole body vibration on lumbar muscle size, intervertebral disk and spinal morphology changes, and low back pain (LBP) incidence during prolonged bed rest, 24 subjects underwent 60 days of head-down tilt bed rest and performed either resistive vibration exercise (n = 7), resistive exercise only (n = 8), or no exercise (n = 9; 2nd Berlin Bed-Rest Study). Discal and spinal shape was measured from sagittal plane magnetic resonance images. Cross-sectional areas (CSAs) of the multifidus, erector spinae, quadratus lumborum, and psoas were measured on para-axial magnetic resonance images. LBP incidence was assessed with questionnaires at regular intervals. The countermeasures reduced CSA loss in the multifidus, lumbar erector spinae and quadratus lumborum muscles, with greater increases in psoas muscle CSA seen in the countermeasure groups (P ≤ 0.004). There was little statistical evidence for an additional effect of whole body vibration above resistive exercise alone on these muscle changes. Exercise subjects reported LBP more frequently in the first week of bed rest, but this was only significant in resistive exercise only (P = 0.011 vs. control, resistive vibration exercise vs. control: P = 0.56). No effect of the countermeasures on changes in spinal morphology was seen (P ≥ 0.22). The results suggest that high-load resistive exercise, with or without whole body vibration, performed 3 days/wk can reduce lumbar muscle atrophy, but further countermeasure optimization is required.

The 2nd Berlin BedRest Study: protocol and implementation

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p < .0001), though similarly in all groups (p > or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed.

Evidence for an additional effect of whole-body vibration above resistive exercise alone in preventing bone loss during prolonged bed rest

SUMMARY: The addition of whole-body vibration to high-load resistive exercise may provide a better stimulus for the reduction of bone loss during prolonged bed rest (spaceflight simulation) than high-load resistive exercise alone. INTRODUCTION: Prior work suggests that the addition of whole-body vibration to high-load resistive exercise (RVE) may be more effective in preventing bone loss in spaceflight and its simulation (bed rest) than resistive exercise alone (RE), though this hypothesis has not been tested in humans. METHODS: Twenty-four male subjects as part of the 2nd Berlin Bed Rest Study performed RVE (n = 7), RE (n = 8) or no exercise (control, n = 9) during 60-day head-down tilt bed rest. Whole-body, spine and total hip dual X-ray absorptiometry (DXA) measurements as well as peripheral quantitative computed tomography measurements of the tibia were conducted during bed rest and up to 90 days afterwards. RESULTS: A better retention of bone mass in RVE than RE was seen at the tibial diaphysis and proximal femur (p ≤ 0.024). Compared to control, RVE retained bone mass at the distal tibia and DXA leg sub-region (p ≤ 0.020), but with no significant difference to RE (p ≥ 0.10). RE impacted significantly (p = 0.038) on DXA leg sub-region bone mass only. Calf muscle size was impacted similarly by both RVE and RE. On lumbar spine DXA, whole-body DXA and calcium excretion measures, few differences between the groups were observed. CONCLUSIONS: Whilst further countermeasure optimisation is required, the results provide evidence that (1) combining whole-body vibration and high-load resistance exercise may be more efficient than high-load resistive exercise alone in preventing bone loss at some skeletal sites during and after prolonged bed rest and (2) the effects of exercise during bed rest impact upon bone recovery up to 3 months afterwards.

The effects of rehabilitation on the muscles of the trunk following prolonged bed rest

Microgravity and inactivity due to prolonged bed rest have been shown to result in atrophy of spinal extensor muscles such as the multifidus, and either no atrophy or hypertrophy of flexor muscles such as the abdominal group and psoas muscle. These effects are long-lasting after bed rest and the potential effects of rehabilitation are unknown. This two-group intervention study aimed to investigate the effects of two rehabilitation programs on the recovery of lumbo-pelvic musculature following prolonged bed rest. 24 subjects underwent 60 days of head down tilt bed rest as part of the 2nd Berlin BedRest Study (BBR2-2). After bed rest, they underwent one of two exercise programs, trunk flexor and general strength (TFS) training or specific motor control (SMC) training. Magnetic resonance imaging of the lumbo-pelvic region was conducted at the start and end of bed rest and during the recovery period (14 and 90 days after re-ambulation). Cross-sectional areas (CSAs) of the multifidus, psoas, lumbar erector spinae and quadratus lumborum muscles were measured from L1 to L5. Morphological changes including disc volume, spinal length, lordosis angle and disc height were also measured. Both exercise programs restored the multifidus muscle to pre-bed-rest size, but further increases in psoas muscle size were seen in the TFS group up to 14 days after bed rest. There was no significant difference in the number of low back pain reports for the two rehabilitation groups (p=.59). The TFS program resulted in greater decreases in disc volume and anterior disc height. The SMC training program may be preferable to TFS training after bed rest as it restored the CSA of the multifidus muscle without generating potentially harmful compressive forces through the spine.

Differential atrophy of the postero-lateral hip musculature during prolonged bedrest and the influence of exercise countermeasures

As part of the 2nd Berlin BedRest Study (BBR2-2), we investigated the pattern of muscle atrophy of the postero-lateral hip and hamstring musculature during prolonged inactivity and the effectiveness of two exercise countermeasures. Twenty-four male subjects underwent 60 days of head-down tilt bedrest and were assigned to an inactive control (CTR), resistive vibration exercise (RVE), or resistive exercise alone (RE) group. Magnetic resonance imaging (MRI) of the hip and thigh was taken before, during, and at end of bedrest. Volume of posterolateral hip and hamstring musculature was calculated, and the rate of muscle atrophy and the effect of countermeasure exercises were examined. After 60 days of bedrest, the CTR group showed differential rates of muscle volume loss (F = 21.44; P ≤ 0.0001) with fastest losses seen in the semi-membranosus, quadratus femoris and biceps femoris long head followed by the gluteal and remaining hamstring musculature. Whole body vibration did not appear to have an additional effect above resistive exercise in preserving muscle volume. RE and RVE prevented and/or reduced muscle atrophy of the gluteal, semi-membranosus, and biceps femoris long head muscles. Some muscle volumes in the countermeasure groups displayed faster recovery times than the CTR group. Differential atrophy occurred in the postero-lateral hip musculature following a prolonged period of unloading. Short-duration high-load resistive exercise during bedrest reduced muscle atrophy in the mono-articular hip extensors and selected hamstring muscles. Future countermeasure design should consider including isolated resistive hamstring curls to target this muscle group and reduce the potential for development of muscle imbalances.

Muscle atrophy and changes in spinal morphology: is the lumbar spine vulnerable after prolonged bed-rest?

STUDY DESIGN: prospective longitudinal study. OBJECTIVE: to evaluate the effect of bed-rest on the lumbar musculature and soft-tissues. SUMMARY OF BACKGROUND DATA: earlier work has suggested that the risk of low back injury is higher after overnight bed-rest or spaceflight. Changes in spinal morphology and atrophy in musculature important in stabilizing the spine could be responsible for this, but there are limited data on how the lumbar musculature and vertebral structures are affected during bed-rest. METHODS: nine male subjects underwent 60-days head-down tilt bed-rest as part of the second Berlin Bed-Rest Study. Disc volume, intervertebral spinal length, intervertebral lordosis angle, and disc height were measured on sagittal plane magnetic resonance images. Axial magnetic resonance images were used to measure cross-sectional areas (CSAs) of the multifidus (MF), erector spinae, quadratus lumborum, and psoas from L1 to L5. Subjects completed low back pain (LBP) questionnaires for the first 7-days after bed-rest. RESULTS: increases in disc volume, spinal length (greatest at lower lumbar spine), loss of the lower lumbar lordosis, and move to a more lordotic position at the upper lumbar spine (P < 0.0097) were seen. The CSAs of all muscles changed (P < 0.002), with the rate of atrophy greatest at L4 and L5 in MF (P < 0.002) and at L1 and L2 in the erector spinae (P = 0.0006). Atrophy of the quadratus lumborum was consistent throughout the muscle (P = 0.15), but CSA of psoas muscle increased (P < 0.0001). Subjects who reported LBP after bed-rest showed, before reambulation, greater increases in posterior disc height, and greater losses of MF CSA at L4 and L5 than subjects who did not report pain (all P < 0.085). CONCLUSION: these results provide evidence that changes in the lumbar discs during bed-rest and selective atrophy of the MF muscle may be important factors in the occurrence of LBP after prolonged bed-rest.

Limited effect of fly-wheel and spinal mobilization exercise countermeasures on lumbar spine deconditioning during 90 d bed-rest in the Toulouse LTBR study

We examined the effect of high-load fly-wheel (targeting the lower-limb musculature and concurrent loading of the spine via shoulder restraints) and spinal movement countermeasures against lumbar spine muscle atrophy, disc and spinal morphology changes and trunk isokinetic torque loss during prolonged bed-rest. Twenty-four male subjects underwent 90 d head-down tilt bed-rest and performed either fly-wheel (FW) exercises every three days, spinal movement exercises in lying five times daily (SpMob), or no exercise (Ctrl). There was no significant impact of countermeasures on losses of isokinetic trunk flexion/extension (p≥0.65). Muscle volume change by day-89 of bed-rest in the psoas, iliacus, lumbar erector spinae, lumbar multifidus and quadratus lumborum, as measured via magnetic resonance imaging (MRI), was statistically similar in all three groups (p≥0.33). No significant effect on MRI-measures of lumbar intervertebral disc volume, spinal length and lordosis (p≥0.09) were seen either, but there was some impact (p≤0.048) on axial plane disc dimensions (greater reduction than in Ctrl) and disc height (greater increases than in Ctrl). MRI-data from subjects measured 13 and 90-days after bed-rest showed partial recovery of the spinal extensor musculature by day-13 after bed-rest with this process complete by day-90. Some changes in lumbar spine and disc morphology parameters were still persistent 90-days after bed-rest. The present results indicate that the countermeasures tested were not optimal to maintain integrity of the spine and trunk musculature during bed rest. © 2011 Elsevier Ltd.

Bone structure and density via HR-pQCT in 60d bed-rest, 2-years recovery with and without countermeasures

We examined the effects of bed-rest, recovery and exercise countermeasures on bone density and structure at the distal tibia and radius as measured via high-resolution peripheral computed tomography. 24 subjects underwent 60-days of head-down tilt bed-rest and performed either resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8) or no exercise (n = 9; 2nd Berlin BedRest Study; BBR2-2). Measurements were performed regularly during and up to 2-years after 60d bed-rest. At the distal tibia marked reductions in cortical area, cortical thickness and bone density but increases in periosteal perimeter and trabecular area were seen (p all<0.001). Recovery of most parameters occurred within 180d after bed-rest. At the distal radius, persistent increases in cortical area, cortical thickness, cortical density and total density and decreases in trabecular area were seen (p all ≤ 0.005). A significant effect of RVE (p = 0.003), but not RE, was seen on cortical area at the distal tibia, with few effects of the countermeasures observed on the remaining parameters. The current study represents the first implementation of high-resolution peripheral computed tomography in bed-rest in male subjects and helps to understand the patterns of bone remodeling due to bed-rest and recovery.

WISE-2005: bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity

To better understand the effects of prolonged bed-rest in women, 24 healthy women aged 25 to 40 years participated in 60-days of strict 6° head-down tilt bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8) which performed no countermeasure, an exercise group (EXE, n=8) undertaking a combination of resistive and endurance training or a nutrition group (NUT, n=8), which received a high protein diet. Using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA), bone mineral density (BMD) changes at various sites, body-composition and lower-leg and forearm muscle cross-sectional area were measured up to 1-year after bed-rest. Bone loss was greatest at the distal tibia and proximal femur, though losses in trabecular density at the distal radius were also seen. Some of these bone losses remained statistically significant one-year after bed-rest. There was no statistically significant impediment of bone loss by either countermeasure in comparison to the control-group. The exercise countermeasure did, however, reduce muscle cross-sectional area and lean mass loss in the lower-limb and also resulted in a greater loss of fat mass whereas the nutrition countermeasure had no impact on these parameters. The findings suggest that regional differences in bone loss occur in women during prolonged bed-rest with incomplete recovery of this loss one-year after bed-rest. The countermeasures as implemented were not optimal in preventing bone loss during bed-rest and further development is required.