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Frequency Dependent Effects of Class I Antiarrhythmic Agents Studied in Patients with Implanted Pacemakers
Author(s) -
TAKANAKA CHIEI,
LEE JONG KOOK,
OKAWA MAKOTO,
SUGIYAMA TSUYOSHI,
YAME SEITARO
Publication year - 1994
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/j.1540-8159.1994.tb03808.x
Subject(s) - disopyramide , flecainide , medicine , qrs complex , bolus (digestion) , lidocaine , anesthesia , antiarrhythmic agent , cardiology , heart disease , atrial fibrillation
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 ECCs. 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. These findings indicate that therapeutic doses of Class I agents cause a rate dependent depression of ventricular conduction in humans that is comparable to their blocking effect on cardiac sodium channels.