In spontaneous hypertensive heart failure rats, myofibrillar power and shortening velocity increased at ~12 months but significantly fell at >20 months, coinciding with clinical signs of heart failure.
How do cardiac myofibrillar contractile properties change during the progression from hypertension to decompensated heart failure in a rodent model?
Cardiac myofibrillar power output initially increases during compensated hypertrophy but significantly declines with the transition to overt heart failure, associated with depressed myofilament protein phosphorylation.
Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension 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 heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure.
Hanft et al. (Fri,) conducted a other in Hypertension and decompensated heart failure. Spontaneous hypertensive heart failure (SHHF) model vs. Wistar-Kyoto control rats was evaluated on Myofibrillar contractile properties (rate of force development, loaded shortening velocity, and power). In spontaneous hypertensive heart failure rats, myofibrillar power and shortening velocity increased at ~12 months but significantly fell at >20 months, coinciding with clinical signs of heart failure.