title: Electrophysiology of O-demethyl encainide in a canine model of sustained ventricular tachycardia.
abstract: The antiarrhythmic agent encainide produces marked suppression of ventricular arrhythmias in most patients. However, in some with sustained ventricular tachycardia, worsening of clinical arrhythmias can occur. Since the effects of this agent are mediated by its O-demethyl metabolite in most patients, we have evaluated the effects of O-demethyl encainide in dogs susceptible to the induction of ventricular tachycardia. Nonsedated animals were studied 3-5 days after 90-min left anterior descending coronary artery occlusions. Electrophysiologic evaluations were carried out at baseline, and then during a series of infusions of O-demethyl encainide that achieved low (58 +/- 5 ng/ml) (mean +/- SE), moderate (190 +/- 16 ng/ml), and high (758 +/- 98 ng/ml) plasma concentrations compared with the range seen in patients (50-300 ng/ml). Ventricular tachycardia induction was unaffected by the drug. Effective refractory period was prolonged in a dose-related fashion at both normal and infarcted epicardial sites. However, local electrogram duration was prolonged only in the infarcted zone. We conclude that O-demethyl encainide exerted no consistent effect on susceptibility to induction of ventricular tachycardia in this study. This agent appears to alter infarcted zone conduction disproportionately.
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology; D016700:Encainide / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects; D013610:Tachycardia / Q000503:physiopathology*
chemical_list: D000813:Anilides; D000889:Anti-Arrhythmia Agents; C033635:O-demethylencainide; D016700:Encainide