Pro-arrhythmic effect of nicorandil in isolated rabbit atria and its suppression by tolbutamide and quinidine

Nicorandil, a potent vasodilator substance which exerts its effects through complex mechanisms including K ATP channel activation, has so far been reported to exert antiarrhythmic but not pro-arrhythmic cardiac activity. We now examined the effects of 10 −4 M nicorandil on spontaneously active or electrically driven isolated rabbit atria. Nicorandil (a) significantly reduced the action potential duration at both 50% (by ≃45%) and 80% (by ≃30%) repolarization and the effective refractory period (by ≃25%) and (b) reproducibly induced short periods of tachycardia either in normal Tyrode solution after a single extra-stimulus or in low-potassium media in the absence of extra-stimulation. Quinidine (10 −5 M) or the K ATP channel inhibitor, tolbutamide (10 −5 M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its K ATP channel opener activity and occures essentially when the underlying conditions facilitate re-entry.