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Am J Physiol Heart Circ Physiol 288: H2603-H2610, 2005. First published February 11, 2005; doi:10.1152/ajpheart.01276.2004
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Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets

Hiroshi Ashikaga, James W. Covell, and Jeffrey H. Omens

Departments of Medicine and Bioengineering, University of California-San Diego, La Jolla, California

Submitted 16 December 2004 ; accepted in final form 4 February 2005

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/dtmax: 2,476 ± 203 vs. 2,330 ± 216 mmHg/s, P = not significant (NS)]. Diastolic relaxation was significantly reduced (dP/dtmin: –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.

finite deformation; strain; fiber; sheet; diastolic function



Address for reprint requests and other correspondence: H. Ashikaga, Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr., MSC 1061, Bldg. 10, B1D416, Bethesda, MD 20892-1061 (E-mail: ashikagah{at}nhlbi.nih.gov)




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