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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.