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.