Time-Course of Cardiac Myofibrillar Contractile Properties during the Progression of Rat Hypertensive Heart Failure

Abstract

Heart failure arises, at least in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, calcium handling, and myofibrillar function. The aim of this study was to determine the time-course of changes in myofibrillar functional properties during the progression of heart failure. The rodent spontaneously hypertensive heart failure (SHHF) model was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt clinical signs of heart failure we predicted a marked depression in all these properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and SHHF rats at 3-months, 12-months and 22-months of age. The Wistar-Kyoto control rats were studied to evaluate the time-course myofilament properties associated with normal aging processes compared to myofilaments from rats with a pre-disposition to heart failure. In the control group, force, rates of force development, loaded shortening, and power were unchanged throughout the time-course. Conversely, in the SHHF group, force, force development rates, loaded shortening, and power all tended to increase at 12-months and markedly fell at the 22-month time point, as did the fractional shortening of left ventricles in vivo. Interestingly, the fall in loaded shortening and normalized peak power output corresponded with the onset of clinical signs of heart failure (e.g., labored breathing, ascites, edema). This study indicates that depressed myofibrillar loaded shortening and power output coincides with symptomatic end-stage heart failure.