Mechanical regulation of myocardial growth during volume-overload hypertrophy in the rat

Alteration of hemodynamic preload leads to ventricular growth and remodeling, but the specific diastolic mechanical factors, such as myocardial stress or strain, that regulate the hypertrophic response remain unclear. To assess the relative importance of these factors in a model of volume-overload hypertrophy, we measured passive pressure-strain relationships by using ultrasonic crystals in the left, ventricle (LV) midwall of rats at 1, 2, 4, and 6 wk after an arteriovenous fistula (AVF). Compared with baseline, mean strain in the muscle fiber direction (E-ff) at an end-diastolic (ED) pressure corresponding to the acute elevation in hemodynamic load with AVF increased by 96% from 0.056 +/- 0.028 to 0.110 +/- 0.044 (P < 0.05). E-ff returned to normal levels after 6 wk of remodeling (0.045 +/- 0.029). Fiber stress at ED pressure, computed from an optimized prolate spheroidal finite-element model for each group, increased by 82% in the acute response, rose to 5.8 times normal level at 1 wk, and remained substantially elevated (5.2 times) at 6 wk. Concurrently, stiffness in both fiber and cross-fiber directions was increased in all groups and reached a maximum of 10 times normal values by 6 wk. Collagen area fraction, as measured in picrosirius-stained sections of the LV free wall, was not different between 6 wk and control. Thus we conclude that ED strain, rather than stress, is normalized during volume hypertrophy through changes in ventricular geometry and wall stiffness that appear unrelated to changes in collagen content.