Comparison of the In Vivo Electrophysiological and Proarrhythmic Effects of Amiodarone With Those of a Selective Class III Drug, Sematilide, Using a Canine Chronic Atrioventricular Block Model

Abstract

Amiodarone effectively blocks both the sodium and calcium channels and β-adrenoceptors, in addition to blocking several potassium currents including I_Kr, I_Ks, I_to, I_K1, I_KACh and I_KNa. The incidence of clinical torsade de pointes (TdP) associated with amiodarone has been reported to be low and the present study compared the proarrhythmic potential of amiodarone with that of a selective I_Kr channel blocker, sematilide, using a canine chronic atrioventrucular block model. Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered orally without anesthesia under continuous ECG monitoring. Both drugs prolonged the QT interval, although the onset was faster for sematilide. The high dose of sematilide induced TdP in 3 of 4 animals, which caused their death, but neither the low dose of sematilide nor the 2 dosages of amiodarone induced lethal ventricular arrhythmias. These results suggest that I_Kr channel inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP. (Circ J 2002; 66: 758 - 762)