A Comparison of the Antifibrillatory Effects of Desethylamiodarone to Amiodarone in a Swine Model

Abstract

We evaluated the effect of two different doses of desethylamiodarone (DEA) and amiodarone on the ventricular fibrillation threshold (VFT). We ascertained the VFT in 24 pigs randomized to intravenous DEA, amiodarone, or vehicle. Ventricular fibrillation was induced by pacing the right ventricle by using a primary drive train at a cycle length of 270 ms for eight beats of 2-ms duration each. A secondary train of 20 pulses of 4-ms duration (100 Hz) immediately followed this over a total duration of 200 ms synchronized to the primary drive train. The intensity of the secondary train stimuli current was initially 2 mA and was increased by 2-mA increments until sustained VF with hemodynamic collapse was induced. The minimal current strength needed to induce sustained VF was defined as the VFT measured in mA. DEA (10 mg/kg) increased the VFT significantly over baseline from 13.5+/-4.9 to 23.2+/-8.8 mA (p = 0.0076). Amiodarone, 10 mg/kg, increased the VFT significantly over baseline (mean +/- SD) from 14.4+/-3.6 to 23.8+/-6.1 mA (p = 0.0016). An additional dose of amiodarone (15 mg/kg) increased the VFT to 38.5+/-15.9 mA, which is significantly greater than the VFT derived from lower-dose amiodarone (p = 0.046). We showed that DEA (10 mg/kg) has a similar antifibrillatory effect as 10 mg/kg of amiodarone. We also demonstrated a dose-dependent effect on VFT for amiodarone.

Impact of a Perioperative Prophylaxis Guideline on Post–Cardiothoracic Surgery Atrial Fibrillation

“…15 In addition, amiodarone also provides some direct antiarrhythmic benefit, but a longer period of preoperative amiodarone loading might accentuate these antiarrhythmic benefits because it takes so long to distribute amiodarone in the tissues and to build up concentrations of desethylamiodarone, an active metabolite with appreciable antiarrhythmic efficacy. 16 However, such a strategy of prolonged oral amiodarone therapy would prevent people with more emergent CTS from being able to have amiodarone prophylaxis. 17 One approach would be to offer patients with elective surgeries a longer preoperative loading regimen to maximize the antiarrhythmic effects with a regimen like the one we propose here for emergent patients, but we wanted to advocate for one regimen for both patient types to reduce confusion and enhance adoption.…”

Epicardial electrical heterogeneity after amiodarone treatment increases vulnerability to ventricular arrhythmias under therapeutic hypothermia

“…The ECG parameters, electrophysiological characteristics, and relevant 3D epicardial map parameters were compared and analyzed ( S1 File ). Amiodarone (10 mg/kg) was infused slowly for 20 min [ 20 ], and epicardial mapping was performed after the infusion under TH. Finally, the vulnerability to ventricular arrhythmias was assessed in three pigs via burst ventricular pacing, and the threshold for the induction of ventricular arrhythmias was determined.…”

Effects of amiodarone in a swine model of nortryptiline toxicity

“…We wanted to administer a volume that was similar to the amiodarone and sodium bicarbonate arms to determine the toxic effects of this nortriptyline infusion. Amiodarone has been found to increase the ventricular fibrillatory threshold in a dose-dependent fashion [8]. Utilizing a maximal and safe dose found in a previous swine model, 15 mg/kg of amiodarone would clinically parallel an administered 300 mg bolus [8].…”

“…Amiodarone has been found to increase the ventricular fibrillatory threshold in a dose-dependent fashion [8]. Utilizing a maximal and safe dose found in a previous swine model, 15 mg/kg of amiodarone would clinically parallel an administered 300 mg bolus [8]. The clinical dose of sodium bicarbonate is 1-2 mEq/kg, and thus we administered the first bolus, 1 mEq/kg, to our swine model.…”