Electrophysiological effects of the optical isomers of disopyramide and quinidine in the dog. Dependence on stereochemistry.

Abstract

We studied the electrophysiological effects of the optical isomers of disopyramide and quinidine on canine cardiac Purkinje fibers. Conventional microelectrode techniques were employed to study the effects of racemic disopyramide, (+)-disopyramide, (-)-disopyramide, quinidine, and quinine. Racemic disopyramide, (+)-disopyramide, and quinidine prolonged action potential duration (APD) measured at 90% repolarization. In contrast, (-)-disopyramide and quinine shortened APD. These directionally opposite effects on repolarization were observed throughout 60 minutes exposure to drug and were concentration-dependent. All five components reduced dV/dt of phase 0, increased conduction time, and increased the current requirement for all-or-none depolarization. The effects of all five compounds on dV/dt, conduction time, and current requirements were time- and concentration-dependent. Our results indicate that the stereochemical configurations of disopyramide and quinidine determine their effects on repolarization of cardiac Purkinje fibers.