Chronic Oral Amiodarone but not Dronedarone Therapy Increases Ventricular Defibrillation Threshold During Acute Myocardial Ischemia in a Closed-Chest Animal Model

Abstract

Dronedarone, a recently approved antiarrhythmic drug, has been shown to have fewer side effects than amiodarone, particularly with regard to thyroid and neurologic events. Since the effects of either drug on ventricular defibrillation threshold during ischemia are unknown, the aim of this study was to compare the effects of dronedarone and amiodarone on defibrillation efficacy during ischemia in a closed-chest animal model. Dronedarone (30 mg·kg·d) and amiodarone (20 mg·kg·d) were administered orally for 3 weeks to 19 and 21 pigs, respectively. A control group (no treatment) comprised 19 pigs. A 2-lead endovascular defibrillation system was used. Each biphasic shock was delivered after 8 seconds of ventricular fibrillation. A step-up/step-down protocol was used to calculate mean defibrillation threshold before and 10 minutes after coronary artery occlusion using an angioplasty balloon in the left descending artery. At basal state, defibrillation threshold did not differ between the control (20.8 ± 4.8 J), amiodarone (21.2 ± 2 J), and dronedarone (19.5 ± 3 J) groups. After ischemia, the amiodarone group had a significantly higher defibrillation threshold than the control group (29.6 ± 3 J vs. 21.8 ± 5 J, respectively; P = 0.015), but the dronedarone (22.8 ± 4 J) and control groups had similar defibrillation threshold values. These data indicate that oral dronedarone treatment, unlike oral amiodarone, does not affect defibrillation threshold during ischemia in pigs.