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 KATP 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 approximately 45%) and 80% (by approximately 30%) repolarization and the effective refractory period (by approximately 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 KATP channel inhibitor, tolbutamide (10(-5) M), suppressed the nicorandil-induced arrhythmias. It is suggested that the pro-arrhythmic effect of nicorandil results from its KATP channel opener activity and occurs essentially when the underlying conditions facilitate re-entry.