Duff H J, Rahmberg M, Sheldon R S
Department of Cardiology, University of Calgary, Alberta, Canada.
J Cardiovasc Pharmacol. 1990 Nov;16(5):685-92. doi: 10.1097/00005344-199011000-00001.
Quinidine has multiple electrophysiologic effects, including prolongation of ventricular conduction time, repolarization, and refractoriness. The purpose of this study was to address the relative contributions of these electrophysiologic effects to the enhanced anti-arrhythmic activity observed when quinidine is combined with mexiletine. We compared antiarrhythmic and electrophysiologic effects observed when quinidine or its stereoisomer quinine were combined with mexiletine. Quinine and quinidine both prolong conduction time; however, these agents have divergent effects on ventricular repolarization time and refractoriness. The modest prolongation of conduction time observed with quinine and mexiletine-quinine in the absence of change of ventricular refractoriness was not associated with antiarrhythmic efficacy. The antiarrhythmic efficacy of mexiletine-quinidine exceeds that of mexiletine-quinine, suggesting that the ability of quinidine to prolong refractoriness and repolarization contributes to the antiarrhythmic efficacy of mexiletine-quinidine. Although, both the mexiletine-quinidine combination and quinidine monotherapy prolonged refractoriness to a similar extent, the mexiletine-quinidine combination produced greater antiarrhythmic efficacy and prolonged interventricular conduction within the periinfarct zone to an extent greater than did quinidine alone. We concluded that the role of quinidine in producing enhanced antiarrhythmic activity when combined with mexiletine includes both prolongation of refractoriness and conduction time in the periinfarct zone.
奎尼丁具有多种电生理效应，包括延长心室传导时间、复极化时间和不应期。本研究的目的是探讨这些电生理效应在奎尼丁与美西律联合使用时增强抗心律失常活性方面的相对作用。我们比较了奎尼丁或其立体异构体奎宁与美西律联合使用时的抗心律失常和电生理效应。奎宁和奎尼丁均能延长传导时间；然而，这些药物对心室复极化时间和不应期有不同的影响。在心室不应期无变化的情况下，奎宁和美西律 - 奎宁联合使用时观察到的传导时间适度延长与抗心律失常疗效无关。美西律 - 奎尼丁的抗心律失常疗效超过美西律 - 奎宁，这表明奎尼丁延长不应期和复极化的能力有助于美西律 - 奎尼丁的抗心律失常疗效。虽然美西律 - 奎尼丁联合用药和奎尼丁单药治疗延长不应期的程度相似，但美西律 - 奎尼丁联合用药产生了更大的抗心律失常疗效，并且使梗死周边区的心室间传导延长的程度大于奎尼丁单独使用时。我们得出结论，奎尼丁与美西律联合使用时产生增强抗心律失常活性的作用包括延长梗死周边区的不应期和传导时间。
