Mexiletine-quinidine combination: enhanced antiarrhythmic and electrophysiologic activity in the dog

Combination treatment with mexiletine and quinidine has been shown to be more effective than either monotherapy in the treatment of ventricular tachycardia in humans. The purpose of this study was to assess the electrophysiologic changes which correlated with enhanced antiarrhythmic activity during treatment with the monotherapies and this combination. Twenty-seven dogs with inducible sustained ventricular tachyarrhythmias (VT) late after ischemic injury were treated with mexiletine and quinidine, alone and in combination. Conscious but sedated animals were assigned randomly to receive serial drug treatments. Sustained VT was consistently inducible during serial placebo studies. In 13 dogs who received all four drug treatments (mexiletine, quinidine, combination and placebo) significantly greater antiarrhythmic efficacy was seen with combination therapy (8 of 13) than was seen with mexiletine alone (1 of 13), quinidine alone (3 of 13) and saline (0 of 13) (P less than .005). This enhanced antiarrhythmic activity was paralleled by greater prolongation of intraventricular conduction to the border zone and increase in excitability threshold at the border zone and increase in ventricular effective refractory period in the infarct zone. Serum concentrations of quinidine were 19 +/- 5 microM when given alone and 15 +/- 5 microM when given in combination. Mexiletine concentrations were 3.6 microM when given alone and 4.2 microM when given in combination. In conclusion, mexiletine and quinidine in combination produced enhanced antiarrhythmic activity which was paralleled by electrophysiologic changes occurring in the perinfarct zone. These electrophysiologic changes appear to be correlates of enhanced antiarrhythmic activity.