Protective effects of diltiazem during myocardial ischemia in isolated cat hearts.

The protective effects of diltiazem, a calcium channel blocker, were studied in isolated, blood-perfused cat hearts subjected to 60 or 90 min of global ischemia, followed by reperfusion of 60 or 120 min, respectively. Ischemia-induced alterations of left ventricular (LV) developed pressure (DP) and compliance, measured with an intraventricular fluid-filled latex balloon, were correlated with respiratory activity in vitro of mitochondria isolated from ischemic-reperfused LV myocardium. Nontreated isolated hearts sustained severe declines of LVDP as a result of 60 (-50 +/- 8%) and 90 min (-83 +/- 7%) of ischemia, whereas diltiazem-treated hearts demonstrated only minor losses of LVDP (-17 +/- 8 and -26 +/- 2%). Diltiazem prevented losses of compliance caused by 60 or 90 min of ischemia, which were severe in nontreated hearts after the latter period of ischemia. The progressive deterioration of mechanical function observed in nontreated hearts was paralleled by depressed mitochondrial oxygen consumption and respiratory control. The respiratory activity of mitochondria isolated from cat heart mitochondria. Diltiazem also prevented significant elevations of tissue and mitochondria Ca++ content, reflecting inhibition of Ca++ influx during ischemia and reperfusion. Also, recovery of ATP levels was greater after 60 min each of ischemia and reperfusion in diltiazem-treated hearts. Thus, diltiazem exerts direct, cardioprotective effects during myocardial ischemia, presumably by inhibiting transmembrane Ca++ fluxes.