Electrophysiological effects of encainide and its metabolites in normal canine Purkinje fibers and Purkinje fibers surviving infarction.
In this study, we assessed the effects of O-demethyl encainide (0.5 microM), the most active metabolite of encainide, and the combination with 3-methoxy-O-demethyl encainide (0.5 microM) and encainide (0.1 microM) on cardiac action potential characteristics in normal canine Purkinje fibers and Purkinje fibers surviving 24 h of myocardial ischemia. O-demethyl encainide decreased Vmax and conduction in normal Purkinje fibers and Purkinje fibers surviving infarction. Further decreases were observed with the combination. Action potential duration at both 50 and 95% repolarization was decreased by O-demethyl encainide. The combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide had no further effect. The combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide produced a smaller change in effective refractory period than O-demethyl encainide in normal Purkinje fibers and in Purkinje fibers surviving infarction. O-demethyl encainide and the combination shifted the membrane responsiveness curve to more negative potentials in both normal Purkinje fibers and Purkinje fibers surviving infarction. It is apparent from this study that there are differences in the effects of O-demethyl encainide and the combination of O-demethyl encainide, 3-methoxy-O-demethyl encainide, and encainide in normal Purkinje fibers compared with Purkinje fibers surviving infarction. Also, the combination used in this study had different electrophysiological effects than those of O-demethyl encainide alone.
Kinnaird
A A
AA
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Man
R Y
RY
D000200:Action Potentials / Q000187:drug effects; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D016700:Encainide / Q000031:analogs & derivatives; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000503:physiopathology
D000813:Anilides; D000889:Anti-Arrhythmia Agents; C033635:O-demethylencainide; C033636:3-methoxy-O-demethylencainide; D016700:Encainide