EFFECTS OF AMIODARONE AND ITS ACTIVE METABOLITE DESETHYLAMIODARONE ONTHE VENTRICULAR DEFIBRILLATION THRESHOLD

Objectives. We evaluated whether the reported difference in the ventri cular defibrillation threshold (DFT) between short-term intravenous an d oral amiodarone is due to the effect of amiodarone's active metaboli te desethylamiodarone (DEA). Background. Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD) , Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect, DEA an active metabolite of a miodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT. Methods. We ascertained the D FT in 24 pigs randomized to receive intravenous amiodarone, DEA or veh icle, Defibrillation was delivered through a transvenous lead system u sing a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in suc cessful defibrillation delivered from ascending and descending serial shocks. Results. Amiodarone caused a dose-response increase in DFT (me an +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035, DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p < 0.01, Addition of 13 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at baseline to 23.1 +/- 7.4 (do se 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p = 0.18. Conclusions. DE A increases DFT by a greater amount than its parent drug amiodarone, T here is an effect of intravenous amiodarone on DFT that is dose depend ent. (C) 1998 by the American College of Cardiology.