Effect of recainam on the energy required for ventricular defibrillation in dogs as assessed with implanted electrodes

Abstract

The effect of recainam (WY-42,362), a new class IC antiarrhythmic drug, on ventricular defibrillation was evaluated with use of implanted superior vena cava and left ventricular patch electrodes in 17 normal dogs anesthetized with sodium pentobarbital. The energy required for a 50% probability of successful defibrillation (E50) was used as the index of ventricular defibrillation threshold. The dogs were classified into three groups: a saline group (n = 6), a low dose recainam group (n = 6) and a high dose recainam group (n = 5). The low dose infusion involved an intravenous loading dose of 3.75 mg/kg body weight over 20 min followed by a maintenance infusion of 0.0375 mg/kg per min. The high dose infusion was double those rates.The low dose recainam infusion produced a plasma recainam concentration of 3.1 ± 0.3 μg/ml and significantly increased QRS duration by 11.3 ± 3% during sinus rhythm. The high dose recainam infusion produced a plasma concentration of 7.7 ± 0.9 μg/ml and significantly increased QRS duration by 27 ± 7% in sinus rhythm. Recainam did not change ventricular effective refractory period or sinus cycle length. The mean change in E50between control and infusion periods was 1 ± 5% in the saline group (8.5 ± 1.4 versus 8.6 ± 1.6 joules); 42 ± 11% in the low dose recainam group (8.1 ± 1.0 versus 11.3 ± 1.3 joules) and 92 ± 17% in the high dose recainam group (11.2 ± 2.1 versus 20.5 ± 2.5 joules). The changes in E50in the two recainam groups were significantly different from those in the saline group and from each other (p < 0.05). It is concluded that recainam elevates the energy required for ventricular defibrillation in a dose-dependent manner.