Electrophysiological Effects of Dronedarone (SR33589), a Noniodinated Benzofuran Derivative, in the Rabbit Heart

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Abstract
Background—To overcome the side effects of amiodarone (AM), its noniodinated analogue, dronedarone (SR), was synthesized. In this study, its electrophysiological effects were compared with those of AM in rabbit hearts. Methods and Results—Five animal groups (n=7 each) for 3 weeks received daily oral treatment of 1 of these regimens: (1) control, vehicle only; (2) AM 50 mg/kg (AM50); (3) AM 100 mg/kg (AM100); (4) SR 50 mg/kg (SR50); and (5) SR 100 mg/kg (SR100). ECGs were recorded before drug and at 3 weeks of drug before euthanasia. Action potentials were recorded from isolated papillary muscle and sinoatrial node by microelectrode techniques. The short-term effects were studied in controls (n=5) at various concentrations of SR (0 to 10 μmol/L) in tissue bath. Action potential duration at 50% (APD50) and 90% (APD90) repolarization and upstroke dV/dt (Vmax) at various cycle lengths were compared by ANOVA with repeated measures. Compared with control, AM and SR increased RR, QT, and QTc intervals (P<0.0001 ...