Mexiletine-quinidine combination: Electrophysiologic correlates of a favorable antiarrhythmic interaction in humans

Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone. The ability of mexiletine monotherapy, quinidine monotherapy and mexiletine-quinidine combination therapy to suppress inducible sustained ventricular tachycardia was related to drug-induced changes in ventricular refractoriness, conduction times and monophasic action potential duration recorded from both ventricles. Ventricular tachycardia could no longer be induced in 7 (35%) of the 20 patients studied with combination therapy. This was a significantly higher proportion of patients than that of the groups responding to either monotherapy (quinidine, 10%; mexiletine, 5%).Ventricular effective and functional refractory periods were measured when applying single (S2), double (S3) and triple (S4) extrastimuli. Quinidine monotherapy increased functional and effective refractory periods of both single and multiple extrastimuli. However, when comparing measurements made during mexiletine treatment with those at baseline, mexiletine monotherapy increased only the refractory periods of S4. The effective refractory period of S4 during mexiletine monotherapy (200 ± 20 ins) was significantly longer than at baseline (160 ± 21 ms). Similarly, when comparing measurements made during combination therapy with those during quinidine monotherapy, combination therapy significantly increased the refractory periods only of multiple extrastimuli. The effective refractory period of S4 during combination therapy (253 ± 26 ms) was significantly longer than that of quinidine monotherapy (223 ± 27 ms). The only other significant difference between combination therapy and monotherapy with either agent was a greater prolongation of conduction time to the left ventricular dyskinetic zone with combination therapy.Therefore, mexiletine-quinidine combination therapy is associated with additional prolongation of the refractory periods of multiple extrastimuli and with further prolongation of conduction into the dyskinetic zone of the left ventricle. These electrophysiologic effects may be markers of enhanced antiarrhythmic activity