Submitted on December 17, 2004
Accepted on February 4, 2005
Diastolic dysfunction in volume overload hypertrophy is associated with abnormal shearing of myolaminar sheets
Hiroshi Ashikaga1*, James W Covell2, and Jeffrey H Omens2
1 Laboratory of Cardiac Energetics, National Heart, Lung and Blood Institute, Bethesda, MD, USA
2 Department of Medicine and Bioengineering, University of California, San Diego, La Jolla, CA, USA
* To whom correspondence should be addressed. E-mail: ashikagah{at}nhlbi.nih.gov.
Diastolic dysfunction in volume overload hypertrophy by aortocaval fistula is characterized by increased passive stiffness of the left ventricle (LV). We hypothesized that the changes in passive properties are associated with abnormal myolaminar sheet mechanics during diastolic filling. We determined 3D finite deformation of myofiber and myolaminar sheets in LV free wall of 6 dogs using cineradiography of implanted markers during development of volume overload hypertrophy by aortocaval fistula. After 9±2 weeks of volume overload, all dogs developed edema of extremities, pulmonary congestion, elevated LVEDP (5±2 vs. 21±4mmHg, P<0.05) and increased LV volume. There was no significant change in systolic function (dP/dtmax 2476±203 vs. 2330±216mmHg/s, P=n.s.). Diastolic relaxation was significantly reduced (dP/dtmin -2466±190 vs. -2076±166mmHg/s, P<0.05; 
32±2 vs. 43±1ms, P<0.05), while duration of diastolic filling was unchanged (304±33 vs. 244±42ms, P=n.s.). 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 the magnitude of fiber stretch was not altered in volume overload (P=n.s.). 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 the motion of radially oriented laminar sheets of the myocardium may play an important functional role in the pathology of diastolic dysfunction in this model.
