Journal of Cardiovascular Pharmacology 2007-12-01

The impact of acute myocardial ischemia on the ventricular defibrillation threshold during chronic oral azimilide therapy.

Philippe Chevalier, Alexis Durand Dubieff, Eric Piqueras, Julien Pineau, Léna Rivard, Elodie Morel, Bernard Bui-Xan, Quadiri Timour

Index: J. Cardiovasc. Pharmacol. 50(6) , 629-32, (2007)

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Abstract

The effects of chronic oral azimilide therapy on the ventricular defibrillation threshold (DFT) during ischemia are unknown. The effects of azimilide on defibrillation efficacy under ischemic condition were investigated in a closed-chest animal model. Azimilide (20 mg/kg/d) was administered orally for 7 days to 10 pigs (20 to 25 kg). The control group (no treatment) comprised 15 pigs. A 2-lead defibrillation system was used. Each shock was delivered after 8 seconds of ventricular fibrillation. A step-up and step-down protocol was used to calculate mean DFT before and 10 minutes after coronary artery occlusion using an angioplasty balloon in the left descending artery. The basal DFT of the azimilide group did not differ from controls (20.8 +/- 4.8 versus 18.8 +/- 2.8; P = 0.33). After ischemia, the mean DFT of the azimilide-treated animals was similar to controls (21.8 +/- 5.2 versus 23.2 +/- 3.8 J; P = 0.54), despite significant lengthening of ventricular repolarisation (428.2 +/- 51.8 versus 494.1 +/- 46.6 msec; P = 0.005) and significant prolongation of the ventricular fibrillation cycle length (85.1 +/- 13 versus 104.7 +/- 24 msec; P < 0.04). Chronic oral azimilide treatment does not affect the DFT at baseline or during acute myocardial ischemia.