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.Cellular & Molecular Immunology advance online publication, 10 November 2014; doi:10.1038/cmi.2014.106.

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.

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.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Low back pain in microgravity and bed rest studies

BACKGROUND: The prevalence of low back pain (LBP) for astronauts in space (68%) is higher than the 1-mo prevalence for the general population on Earth (39%). It is unclear whether differences occur between healthy subjects and astronauts with a history of LBP. Knowledge of this issue is important to assess whether a history of LBP could have an operational impact. METHODS: We evaluated LBP prospectively during short duration spaceflight (15 d; N=20) and compared this with similar data collected during two bed rest studies (N=40). Astronauts completed a questionnaire 5-10 d preflight, during each flight day, and 5-10 d postflight. RESULTS: All astronauts with a history of LBP also developed LBP in flight. These astronauts reported a significantly longer duration of LBP and a different pain location. LBP was most often experienced in the central area of the lower back during spaceflight with an incidence of 70% and a mean pain level of 3 (on a scale of 0-10). Pain resolved within 10 d of flight. No neurological signs were present. The most frequently reported countermeasure was assuming a "knees to chest (fetal tuck) position" combined with stretching. Greater LBP intensity was reported in spaceflight than bed rest with a trend indicating a greater number of days of pain during spaceflight. DISCUSSION: The current study represents a prospective study of LBP in spaceflight. The results indicate that LBP is self-limiting in spaceflight and should not pose an operational risk. Prior LBP on Earth appears to be a risk factor for LBP in spaceflight.

Resistive vibration exercise reduces lower limb muscle atrophy during 56-day bed-rest

OBJECTIVES: The current study aimed to examine the effectiveness of a resistive vibration exercise countermeasure during prolonged bed-rest in preventing lower-limb muscle atrophy. METHODS: 20 male subjects underwent 56-days of bed-rest and were assigned to either an inactive control, or a countermeasure group which performed high-load resistive exercises (including squats, heel raises and toe raises) with whole-body vibration. Magnetic resonance imaging of the lower-limbs was performed at two-weekly intervals. Volume of individual muscles was calculated. RESULTS: Countermeasure exercise reduced atrophy in the triceps surae and the vastii muscles (F>3.0, p<.025). Atrophy of the peroneals, tibialis posterior and toe flexors was less in the countermeasure-subjects, though statistical evidence for this was weak (F

Resistive simulated weightbearing exercise with whole body vibration reduces lumbar spine deconditioning in bed-rest

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: Determine the effectiveness a resistive exercise countermeasure with whole-body vibration in relation to lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight (bed-rest). SUMMARY OF BACKGROUND DATA: Spinal lengthening, flattening of the spinal curves, increases in disc size, and muscle atrophy are commonly seen in spaceflight simulation. This may represent a risk for low back injury. Consideration of exercise countermeasures against these changes is critical for success of long-term spaceflight missions. METHODS: Twenty healthy male subjects underwent 8-weeks of bed-rest with 6-months follow-up and were randomly allocated to an inactive control or countermeasure exercise group. Magnetic resonance imaging of the lumbo-pelvic region was conducted at regular time-points during and after bed-rest. Using uniplanar images at L4, cross-sectional areas of the multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral abdominal, and rectus abdominis muscles were measured. Sagittal scans were used to assess lumbar spine morphology (length, sagittal disc area and height, and intervertebral angles). RESULTS: The countermeasure group exhibited less multifidus muscle atrophy (P = 0.024) and its atrophy did not persist long-term as in the control group (up to 3-months; P < 0.006). Spinal lengthening (P = 0.03) and increases in disc area (P = 0.041) were also reduced. Significant partial correlations (P < 0.001) existed between spinal morphology and muscle cross-sectional area changes. CONCLUSION: The resistive vibration exercise countermeasure reduced, but did not entirely prevent, multifidus muscle atrophy and passive spinal tissue deconditioning during bed-rest. Atrophy of the multifidus muscles was persistent long-term in the inactive subjects. Future work could consider closer attention to spinal posture during exercise and optimizing exercise dose.

Resistive exercise versus resistive vibration exercise to counteract vascular adaptations to bed rest

Bed rest results in marked vascular adaptations, and resistive vibration exercise (RVE) has been shown to be an effective countermeasure. As vibration exercise has practical and logistical limitations, the use of resistive exercise (RES) alone has the preference under specific circumstances. However, it is unknown if RES is sufficient to prevent vascular adaptations to bed rest. Therefore, the purpose of the present study was to examine the impact of RES and RVE on the vascular function and structure of the superficial femoral artery in young men exposed to 60 days of bed rest. Eighteen healthy men (age: 31 +/- 8 yr) were assigned to bed rest and randomly allocated to control, RES, or RVE groups. Exercise was applied 3 times/wk for 5-7 min/session. Resting diameter, blood flow, flow-mediated dilation (FMD), and dilator capacity of the superficial femoral artery were measured using echo-Doppler ultrasound. Bed rest decreased superficial femoral artery diameter and dilator capacity (P < 0.001), which were significantly attenuated in the RVE group (P < 0.01 and P < 0.05, respectively) but not in the RES group (P = 0.202 and P = 0.696, respectively). Bed rest significantly increased FMD (P < 0.001), an effect that was abolished by RVE (P < 0.005) but not RES (P = 0.078). Resting and hyperemic blood flow did not change in any of the groups. Thus, RVE abolished the marked increase in FMD and decrease in baseline diameter and dilator capacity normally associated with prolonged bed rest. However, the stimulus provided by RES alone was insufficient to counteract the vascular adaptations to bed rest.

Bed rest and cognition: effects on executive functioning and reaction time

INTRODUCTION: Executive functions are high-order aspects of cognition heavily dependent upon the prefrontal cortex. Both prefrontal cortex activity and executive function task performance are enhanced by participation in aerobic physical activity, suggesting that a lack of such activity during the bed rest model of prolonged weightlessness might induce executive function deficits. METHODS: Twenty-four healthy males (ages 21-45 yr) undertook 60 d of head-down bed rest (-6 degrees) for the 2nd Berlin Bed Rest Study (BBR2-2). Three executive function tasks (Iowa Gambling Task, working memory, and flanker) and a reaction time task were administered before, during, and after bed rest. RESULTS: Iowa Gambling Task scores were significantly worse during bed rest (1.7 +/- 6.9) than in other sessions (24.3 +/- 7.8). Effects on working memory and flanker task performance were less obvious, requiring practice effects to be considered. Reaction time was significantly slower after bed rest (569 +/- 42 ms) than in earlier tests (529 +/- 45 ms). There was also significantly less intrasubject variability in reaction time after bed rest, consistent with more efficient executive functioning at this stage. DISCUSSION: Our results provide some evidence for a detrimental effect of bed rest on executive functioning. Whether this stems from a lack of aerobic physical activity and/or changes in the prefrontal cortex remains to be determined. Cognitive effects of bed rest could have implications for the planned human exploration of Mars, and for medical and lifestyle conditions with inadequate levels of aerobic physical activity.

Influence of vibration resistance training on knee extensor and plantar flexor size, strength, and contractile speed characteristics after 60 days of bed rest

Spaceflight and bed rest (BR) result in loss of muscle mass and strength. This study evaluated the effectiveness of resistance training and vibration-augmented resistance training to preserve thigh (quadriceps femoris) and calf (triceps surae) muscle cross-sectional area (CSA), isometric maximal voluntary contraction (MVC), isometric contractile speed, and neural activation (electromyogram) during 60 days of BR. Male subjects participating in the second Berlin Bed Rest Study underwent BR only [control (CTR), n = 9], BR with resistance training (RE; n = 7), or BR with vibration-augmented resistance training (RVE; n = 7). Training was performed three times per week. Thigh CSA and MVC torque decreased by 13.5 and 21.3%, respectively, for CTR (both P < 0.001), but were preserved for RE and RVE. Calf CSA declined for all groups, but more so (P < 0.001) for CTR (23.8%) than for RE (10.7%) and RVE (11.0%). Loss in calf MVC torque was greater (P < 0.05) for CTR (24.9%) than for RVE (12.3%), but not different from RE (14.8%). Neural activation at MVC remained unchanged in all groups. For indexes related to rate of torque development, countermeasure subjects were pooled into one resistance training group (RT, n = 14). Thigh maximal rate of torque development (MRTD) and contractile impulse remained unaltered for CTR, but MRTD decreased 16% for RT. Calf MRTD remained unaltered for both groups, whereas contractile impulse increased across groups (28.8%), despite suppression in peak electromyogram (12.1%). In conclusion, vibration exposure did not enhance the efficacy of resistance training to preserve thigh and calf neuromuscular function during BR, although sample size issues may have played a role. The exercise regimen maintained thigh size and MVC strength, but promoted a loss in contractile speed. Whereas contractile speed improved for the calf, the exercise regimen only partially preserved calf size and MVC strength. Modification of the exercise regimen seems warranted.

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.

Effect of prolonged bed rest on the anterior hip muscles

Prolonged bed rest and inactivity is known to cause muscular atrophy with previous research indicating that muscles involved in joint stabilisation are more susceptible. The anterior hip muscles are important for hip joint function and stability but little is known about the effects of prolonged inactivity on their function. This study investigated the effect of prolonged bed rest on the size of the anterior hip muscles and their pattern of recovery. The effect of resistive vibration exercise (RVE) as a countermeasure to muscle atrophy was also investigated. 12 male participants, randomly assigned to either a control or an exercise group, underwent 8 weeks of bed rest with 6 months follow-up. Changes in muscle cross-sectional area (CSA) of the iliacus, psoas, iliopsoas, sartorius and rectus femoris muscles were measured by magnetic resonance imaging at regular intervals during bed rest and recovery phases. CSAs of iliopsoas and sartorius decreased at the hip joint (p<0.05) during bed rest but iliacus, psoas, and rectus femoris CSAs were unchanged (p>0.05). No significant difference was found between the two groups for all muscles (all p>0.1), suggesting inefficacy of the countermeasure in this sample. These findings suggest that prolonged bed rest can result in the atrophy of specific muscles across the hip joint which may affect its stability and function.

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.

Impact of bed rest on conduit artery remodeling: effect of exercise countermeasures

Physical inactivity is a potent stimulus for vascular remodeling, leading to a marked decrease in conduit artery diameter. However, little is known about the impact of physical inactivity on artery wall thickness or wall:lumen ratio or the potential of exercise countermeasures to modify artery wall thickness. The purpose of the study was to examine the impact of 60 days of bed rest, with or without exercise countermeasures, on carotid and superficial femoral artery wall thickness. Eighteen men were assigned to bed rest (second Berlin Bed Rest Study) and randomly allocated to control, resistive exercise, or resistive vibration exercise. Both exercise countermeasures were applied 3 times per week while the subjects were in the supine position on the bed. Sonography was used to examine baseline diameter and wall thickness of the carotid and femoral arteries. Bed rest decreased diameter of the superficial femoral artery (P=0.001) but not the carotid artery (P=0.29). Bed rest induced a significant increase in carotid and superficial femoral artery wall thickness (P=0.007 and 0.03) and wall:lumen ratio (P=0.009 and 0.001). Exercise prevented the increase in wall thickness of the carotid artery. In addition, exercise partly prevented the increased wall:lumen ratio in the superficial femoral artery. In conclusion, 8 weeks of bed rest resulted in approximately 20% increase in conduit artery wall thickness. Exercise countermeasures completely (carotid artery) or partly (superficial femoral artery) abolished the increase in wall thickness. These findings suggest that conduit artery wall thickness, a vascular characteristic associated previously with atherosclerosis, can rapidly adapt to physical inactivity and exercise in humans.