Cardiovascular research
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Cardiovascular research · Jul 1989
Mexiletine-quinidine in isolated hearts: an interaction involving the sodium channel.
Combination therapy with mexiletine and quinidine has been shown to be more effective than either monotherapy in treating patients with ventricular tachycardia. This enhanced efficacy was associated with prolongation of ventricular refractoriness and conduction time in the infarct zone. As sodium channel activity is a determinant of both conduction time and refractoriness we formed the hypothesis that the mexiletine-quinidine interaction was due at least in part to interactions involving the sodium channel. ⋯ The combination of similarly low concentrations of tetrodotoxin and quinidine also produced enhanced anti-arrhythmic efficacy and enhanced prolongation of ventricular refractoriness and conduction which mimicked the effect of mexiletine and quinidine in combination. In contrast, the combination of mexiletine and tetrodotoxin did not produce enhanced anti-arrhythmic and electrophysiological activity. Since tetrodotoxin is a highly specific sodium channel blocker, these data suggest that the enhanced antiarrhythmic activity of mexiletine-quinidine combination therapy involves, at least in part, blockade of the cardiac sodium channel.