In a canine chronic atrioventricular block model, high-dose sematilide induced torsade de pointes in 75% of animals, whereas amiodarone induced no lethal ventricular arrhythmias.
Does amiodarone have a lower proarrhythmic potential compared to sematilide in a canine chronic atrioventricular block model?
Amiodarone showed a lower risk of inducing torsade de pointes compared to the selective IKr blocker sematilide in a canine model, likely due to its multi-channel blocking properties.
Absolute Event Rate: 0% vs 75%
Amiodarone effectively blocks both the sodium and calcium channels and beta-adrenoceptors, in addition to blocking several potassium currents including IKr, IKs, Ito, IK1, IKACh and IKNa. 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 IKr 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 IKr channel inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP.
Yoshida et al. (Tue,) conducted a other in Chronic atrioventricular block (animal model) (n=16). Amiodarone vs. Sematilide (3 and 30 mg/kg) was evaluated on Induction of torsade de pointes (TdP). In a canine chronic atrioventricular block model, high-dose sematilide induced torsade de pointes in 75% of animals, whereas amiodarone induced no lethal ventricular arrhythmias.