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Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance
BACKGROUND: The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. METHODS AND RESULTS: We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm-V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9 mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% (P<.10). CONCLUSIONS: Two weeks of head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.
Submaximal exercise VO2 and Qc during 30-day 6 degrees head-down bed rest with isotonic and isokinetic exercise training
BACKGROUND: Maintaining intermediary metabolism is necessary for the health and well-being of astronauts on long-duration spaceflights. While peak oxygen uptake (VO2) is consistently decreased during prolonged bed rest, submaximal VO2 is either unchanged or decreased. METHODS: Submaximal exercise metabolism (61 +/- 3% peak VO2) was measured during ambulation (AMB day-2) and on bed rest days 4, 11, and 25 in 19 healthy men (32-42 yr) allocated into no exercise (NOE, N = 5) control, and isotonic exercise (ITE, N = 7) and isokinetic exercise (IKE, N = 7) training groups. Exercise training was conducted supine for two 30-min periods per day for 6 d per week: ITE training was intermittent at 60-90% peak VO2; IKE training was 10 sets of 5 repetitions of peak knee flexion-extension force at a velocity of 100 degrees s-1. Cardiac output was measured with the indirect Fick CO2 method, and plasma volume with Evans blue dye dilution. RESULTS: Supine submaximal exercise VO2 decreased significantly (*p < 0.05) by 10.3%* with ITE and by 7.3%* with IKE; similar to the submaximal cardiac output decrease of 14.5%* (ITE) and 20.3%* (IKE), but different from change in peak VO2 (+1.4% with ITE and -10.2%* with IKE) and decrease in plasma volume of -3.7% (ITE) and -18.0%* (IKE). Reduction of submaximal VO2 during bed rest correlated 0.79 (p < 0.01) with submaximal Qc, but was not related to change in peak VO2 or plasma volume. CONCLUSION: Reduction in submaximal oxygen uptake during prolonged bed rest is related to decrease in exercise but not resting cardiac output; perturbations in active skeletal muscle metabolism may be involved.
Alterations in skeletal muscle related to impaired physical mobility: an empirical model
The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type IIa muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (micron 2). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility.
Bone mineral loss and recovery after 17 weeks of bed rest
The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88.