Frequency dependent effects of class I antiarrhythmic agents studied in patients with implanted pacemakers.
Use and frequency dependency are common properties of Class I antiarrhythmic agents, which block cardiac sodium channels in vitro. The purpose of this study was to examine the rate dependent effects of Class I agents on ventricular conduction in humans in a crossover fashion. Twelve patients with implanted pacemakers who required antiarrhythmic therapy were studied. Four Class I agents were administered as follows: lidocaine, 1 mg/kg bolus followed by 4 mg/min infusion; disopyramide, 1 mg/kg bolus followed by 0.02 mg/kg per hour; aprindine, 1 mg/kg bolus followed by 4 mg/min infusion; and flecainide, 100 mg/day orally for 1 week. Trains of ventricular test stimuli between 70-180 ppm were applied during stable VVI pacing at 60 ppm. QRS duration was determined using signal-averaged as well as standard ECGs. Lidocaine produced significant QRS prolongation at rates > 110 ppm (3.0% +/- 1.4% at 120 ppm, P < 0.05; 7.2% +/- 1.8% at 180 ppm, P < 0.01). Aprindine, disopyramide, and flecainide produced significant QRS prolongation at rates as low as 70 ppm and in a frequency dependent manner: 12.7% +/- 1.5%, 9.6% +/- 1.6%, and 13.3% +/- 2.8% at 70 ppm, respectively, (P < 0.01); 21.6% +/- 0.6%, 14.7% +/- 2.4%, and 29.9% +/- 4.2% at 180 ppm, respectively, (P < 0.01). Time constants of the single exponential development of QRS prolongation when the pacing rate was abruptly increased to 150 ppm were 0.09 +/- 0.02 sec for lidocaine, 5.1 +/- 1.2 sec for aprindine, 8.1 +/- 1.7 sec for disopyramide, and 11.9 +/- 1.4 sec for flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiology Section, Hamamatsu Medical Center, Japan.
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Takanaka
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Lee
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Nonokawa
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Sugiyama
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Yame
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001073:Aprindine / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy; D002304:Cardiac Pacing, Artificial; D018592:Cross-Over Studies; D004206:Disopyramide / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects*; D005424:Flecainide / Q000494:pharmacology; D006801:Humans; D008012:Lidocaine / Q000627:therapeutic use; D010138:Pacemaker, Artificial
D000889:Anti-Arrhythmia Agents; D001073:Aprindine; D008012:Lidocaine; D004206:Disopyramide; D005424:Flecainide