Assessment of the antiarrhythmic activity of nicorandil during myocardial ischemia and reperfusion

The potential pro- and antiarrhythmiceffects of nicorandil (1–100 μM) were assessed in isolated rat hearts subjected to coronary artery ligation and reperfusion under conditions of normal (5.9 mM) and lowered (3.2 mM) perfusate K +. Nicorandil dose dependently increased coronary flow, induced a moderate negative inotropic effect but had no chronotropic effects. During ligation (15 min), only high concentrations of nicorandil (50 and 100 μM) significantly reduced the incidence of ventricular premature beats and ventricular tachycardia in normal perfusate, but ventricular fibrillation was observed in 2 9 hearts. No antiarrhytmic effects were observed with hypokalemic conditions. During reperfusion, nicorandil was associated with a more rapid degeneration into ventricular fibrillation in normal perfusate while the incidence of ventricular fibrillation was only reduced by 100 μM nicorandil. No antiarrhythmic effects were observed during reperfusion with lowered K + and all drug-treated hearts demonstrated irreversible ventricular fibrillation. Nicorandil perfusion (50 μM; 5.9 mM K +) did not affect the depression of ATP or elevation of lactate within the ischemic tissue during coronary artery ligation. These data do not support an effect of nicorandil against ischemia- or reperfusion-induced arrhytmias in the intact heart in vitro and may suggest a proarrhythmic effect particularly at lowered K + concentrations.