title: Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction.
abstract: 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.
authors.affiliation: Department of Circulation, Nagoya University, Japan.
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Takanaka
authors.forename: M
authors.initials: M
authors.lastname: Nonokawa
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Yabe
authors.forename: I
authors.initials: I
authors.lastname: Kodama
authors.forename: J
authors.initials: J
authors.lastname: Toyama
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001073:Aprindine / Q000627:therapeutic use; D002304:Cardiac Pacing, Artificial; D004206:Disopyramide / Q000627:therapeutic use; D004338:Drug Combinations; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D004338:Drug Combinations; D001073:Aprindine; D008012:Lidocaine; D004206:Disopyramide