NICORANDIL SUPPRESSES EARLY AFTERDEPOLARISATION AND VENTRICULAR ARRHYTHMIAS INDUCED BY CESIUM-CHLORIDE IN RABBITS INVIVO

Study objective - Outward K current of cardiac membrane has been shown to be suppressed by caesium chloride (Cs) and enhanced by nicorandil, a coronary vasodilator. The aim of this study was to assess the effects of nicorandil on the Cs induced early afterdepolarisations and associated ventricular arrhythmias in the rabbit heart in vivo. Design - Intravenous bolus injections of Cs (1 mmol.kg-1) were given three times at 20 min intervals. Monophasic action potentials of the left ventricular endocardium and the ECG (lead II) were recorded simultaneously over 60 min, under the intrinisic (sinus node) cardiac rhythm. Experimental material - Eight rabbits were treated with Cs alone (control group); seven other rabbits were first treated with an intravenous infusion of nicorandil (0.2 mg.kg-1) (nicorandil treated group) and the effects of Cs were then examined. Measurements and main results - In the control group, Cs produced early afterdepolarisations, premature ventricular beats and ventricular tachycardias. The ventricular tachycardias included two different types: (1) non-sustained polymorpohic ventricular tachycardia mimicking the torsade de pointes in patients with long QT syndrome; (2) sustained monomorphic ventricular tachycardia. In the nicorandil treated group, the amplitude of the early afterdepolarisations and the incidence of ventricular tachycardias were significantly less than in the control group. Conclusions - Nicorandil suppresses the early afterdepolarisations and ventricular tachyarrhythmias induced by Cs, possibly by increasing the membrane K conductance.