Non-uniform prolongation of intracellular Ca2+ transients recorded from the epicardial surface of isolated hearts from rabbits with heart failure.

Abstract

To study the time course of Ca2+ transients recorded from the left ventricular epicardial surface of isolated hearts from rabbits with heart failure and to correlate the results with mechanical function. Heart failure was induced in the rabbit 8 weeks after coronary ligation (n = 17) with 13 controls. Echocardiography was used to assess in vivo left ventricular dysfunction. The fluorescent indicator Indo-1 was loaded into isolated Langendorff-perfused hearts and Ca2+ transients were recorded from 15 sites over the left ventricular epicardial surface using a single core light guide. The time course of the Ca2+ transients was analysed and the duration measured and correlated with in vitro mechanical function. Significant mechanical dysfunction was produced in this model of heart failure. The mean duration of the Ca2+ transients obtained from failing hearts was prolonged (156.2 +/- 3.2 ms) when compared to controls (124.9 +/- 2.6 ms, P < 0.001). Delayed relaxation as measured by the maximum rate of intraventricular pressure decay was significantly correlated with the prolonged Ca2+ transients (r = -0.63, P < 0.001). In addition, there was increased variation of the Ca2+ transient duration in the failing hearts. Coronary artery ligation-induced heart failure is associated with changes in the surviving myocardium which result in a non-uniform prolongation of Ca2+ transient duration. This suggests that there is a regional heterogeneity to the abnormal intracellular Ca2+ handling in heart failure.