Cicletanine improves myocardial function deteriorated by ischemia/reperfusion in isolated working rat hearts

The effect of cicletanine, a novel furopyridine antihypertensive drug was compared with that of nitrendipine, a dihydropyridine slow calcium channel blocker, on cardiac function and reperfusion-induced ventricular arrhythmias in isolated working rat hearts subjected to 10-min ischemia induced by ligation of the left main coronary artery followed by 10-min reperfusion. Before ischemia, cicletanine and nitrendipine, perfused at concentrations of 3 x 10(-5), 6 x 10(-5), 10(-4), and 2 x 10(-4) or 10(-8) M, respectively, did not influence heart rate (HR), LV developed pressure (LVDP), its first derivative (LVdP/dtmax), and LV end-diastolic pressure (LVEDP), whereas aortic flow (AF) was decreased by 2 x 10(-4) M cicletanine only. Coronary flow (CF) remained unchanged by various cicletanine concentrations but was slightly increased by nitrendipine. In the concentration range of 3 x 10(-5)-10(-4) M, cicletanine improved AF either in ischemia or during reperfusion, whereas 2 x 10(-4) M had no such effect. Nitrendipine slightly attenuated ischemia/reperfusion-induced decrease in AF. Cicletanine and nitrendipine enhanced LVDP during ischemia. Ischemia-induced deterioration of LVdP/dtmax was reduced by cicletanine, during reperfusion, but this parameter was reduced by nitrendipine and the highest cicletanine concentration. Cicletanine decreased LVEDP significantly during ischemia and reperfusion, but nitrendipine had no such effect. All cicletanine concentrations reduced the incidence of irreversible ventricular fibrillation (VF) during reperfusion, an effect roughly concentration dependent in the range of 3 x 10(-5)-10(-4) M, whereas nitrendipine had no influence on arrhythmias.