Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets

Abstract

Diastolic dysfunction in volume-overload hypertrophy by aortocaval fistula is characterized by increased passive stiffness of the left ventricle (LV). We hypothesized that changes in passive properties are associated with abnormal myolaminar sheet mechanics during diastolic filling. We determined three-dimensional finite deformation of myofiber and myolaminar sheets in the LV free wall of six dogs with cineradiography of implanted markers during development of volume-overload hypertrophy by aortocaval fistula. After 9 ± 2 wk of volume overload, all dogs developed edema of extremities, pulmonary congestion, elevated LV end-diastolic pressure (5 ± 2 vs. 21 ± 4 mmHg, P < 0.05), and increased LV volume. There was no significant change in systolic function [dP/d tmax: 2,476 ± 203 vs. 2,330 ± 216 mmHg/s, P = not significant (NS)]. Diastolic relaxation was significantly reduced (dP/d tmin: −2,466 ± 190 vs. −2,076 ± 166 mmHg/s, P < 0.05; time constant of LV pressure decline: 32 ± 2 vs. 43 ± 1 ms, P < 0.05), whereas duration of diastolic filling was unchanged (304 ± 33 vs. 244 ± 42 ms, P = NS). Fiber stretch and sheet shear occur predominantly in the first third of diastolic filling, and chronic volume overload induced remodeling in lengthening of the fiber and reorientation of the laminar sheet architecture. Sheet shear was significantly increased and delayed at the subendocardial layer ( P < 0.05), whereas magnitude of fiber stretch was not altered in volume overload ( P = NS). These findings indicate that enhanced filling in volume-overload hypertrophy is achieved by enhanced sheet shear early in diastole. These results provide the first evidence that changes in motion of radially oriented laminar sheets may play an important functional role in pathology of diastolic dysfunction in this model.