CARDIAC ATROPHY AFTER BED-REST DECONDITIONING - A NONNEURAL MECHANISMFOR ORTHOSTATIC INTOLERANCE

Background The cardiovascular adaptation to bed rest leads to orthosta tic intolerance, characterized by an excessive fall in stroke volume ( SV) in the upright position. We hypothesized that this large fall in S V is due to a change in cardiac mechanics. Methods and Results We meas ured pulmonary capillary wedge pressure (PCWP), SV, left ventricular e nd-diastolic volume (LVEDV), and left ventricular mass (by echocardiog raphy) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-dow n tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curv es were modeled exponentially by P=ae(kV)+b and logarithmically by P=- Sln[(V-m-V)/(V-m-V-0], where V-0 indicates volume at P=0, and the cons tants k and S were used as indices of normalized chamber stiffness. Dy namic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure char acterized the steepness of the Starling curve. We also measured plasma Volume (with Evans blue dye) and maximal orthostatic tolerance. Bed r est led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V-0 (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 c urve. Normalized chamber stiffness was unchanged, but dP/dV was reduce d 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 compli ant portion of the P-V curve. This results in a steeper Starling relat ionship, which contributes to orthostatic intolerance by causing an ex cessive reduction in SV during orthostasis.