NONUNIFORM PROLONGATION OF INTRACELLULAR CA2-FAILURE( TRANSIENTS RECORDED FROM THE EPICARDIAL SURFACE OF ISOLATED HEARTS FROM RABBITS WITH HEART)

Objectives: To study the time course of Ca2+ transients recorded from the left ventricular epicardial surface of isolated hearts from rabbit s with heart failure and to correlate the results with mechanical func tion. Methods: Heart failure was induced in the rabbit 8 weeks after c oronary ligation (n = 17) with 13 controls. Echocardiography was used to assess in vivo left ventricular dysfunction. The fluorescent indica tor Indo-1 was loaded into isolated Langendorff-perfused hearts and Ca 2+ transients were recorded from 15 sites over the left ventricular ep icardial surface using a single core light guide. The time course of t he Ca2+ transients was analysed and the duration measured and correlat ed with in vitro mechanical function. Results: Significant mechanical dysfunction was produced in this model of heart failure. The mean dura tion 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 intravent ricular pressure decay was significantly correlated with the prolonged Ca2+ transients (r = -0.63, P < 0.001). In addition, there was increa sed variation of the Ca2+ transient duration in the bailing hearts. Co nclusions: Coronary artery ligation-induced heart failure is associate d with changes in the surviving myocardium which result in a non-unifo rm prolongation of Ca2+ transient duration. This suggests that there i s a regional heterogeneity to the abnormal intracellular Ca2+ handling in heart failure. (C) 1998 Elsevier Science B.V.