Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction

We investigated the interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction of human hearts in vivo. QRS duration in signal-averaged electrocardiograms and standard electrocardiograms were measured as an index of intraventricular conduction time in 17 patients with implanted pacemakers at various pacing rates (100-180 ppm, VVI mode). Single intravenous administration of lidocaine, disopyramide or aprindine prolonged the QRS of signal-averaged electrocardiograms in a frequency-dependent manner. Lidocaine (n = 17) produced significant QRS prolongation from pre-drug control at rates > or = 120 ppm (6.2 +/- 1.4% at 180 ppm), whereas disopyramide (n = 17) and aprindine (n = 17) did so from the lowest rate (8.9 +/- 1.8% to 12.3 +/- 2.9% at 100-180 ppm with disopyramide; 14.7 +/- 1.3% to 19.3 +/- 2.2% at 100-180 ppm with aprindine). Addition of lidocaine to disopyramide (n = 17) showed an additive effect; QRS prolongation was enhanced significantly by 1.4-2.8% at rates > or = 150 ppm. In contrast, addition of lidocaine to aprindine (n = 17) showed a subtractive effect; the QRS prolongation was attenuated significantly by 1.6-2.4% at rates < 150 ppm. Combined intravenous administration of class-I antiarrhythmic drugs causes not only additive but also subtractive effects on the intraventricular conduction of the human heart, probably through their interaction on the sodium channel receptor.