Comparative Study of the Effects of Dronedarone and Amiodarone on Automaticity of the Sinus Node of the Rabbit

pp 339-350

Abstract

Amiodarone is one of the most effective antiarrhythmic agents used for the treatment of supraventricular and ventricular arrhythmias, possibly due to combination of classI, II,III and IV actions in addition to its interaction with thyroid function. Dronedarone is a new compound structurally related to amiodarone. Unlike amiodarone, dronedarone contains no iodine substituent in its

structure.

Objective

To compare the in vitro electrophysiologic effects of amiodarone and dronedarone on sinus node pace-maker cells.MethodsThe standard microelectrode technique on preparations isolated from the rabbit sinus node was used.

Results

Amiodarone (30 μM,180 min) and dronedarone (10μM, 120 min) prolonged the spontaneous cycle length by 18.3 ± 3.5% (n = 9) and 25.5 ± 4.8% (n = 12), respectively (mean ± SEM), decreased the action potential amplitude by 11.2 ± 4.3% (n = 5) and 25.5 ±5.2% (n = 12), respectively, and decreased the phase 4 slope by 24.6 ± 5.6% (n = 5) and 33.6 ± 7.1% (n = 8), respectively. Addition of isoproterenol (10-2μM) readily reversed the amiodarone and dronedarone-induced depression of automaticity. Dose-response curves in the presence and in the absence of drone-darone showed that dronedarone (10 μM) did not modify the extent of the automatic response to iso-proterenol (5 x 10-3_'5μM).

Conclusion

Dronedarone, as amiodarone, depresses heart rateand sinus node automaticity, probably by means of blockade of the calcium channel. This might be useful for the treatment of supraventricular arrhythmias.