Effects of the phenothiazine analog, EN-313, on ventricular arrhythmias in the dog.
Effects of the phenothiazine analog, EN-313, on ventricular electrical activity were studied using isolated blood-superfused canine Purkinje fibers and conscious dogs with sustained ventricular arrhythmias following a 2-stage ligation of the left anterior descending coronary artery, EN-313, less than 3 mg/kg, i.v., had no significant effect on transmembrane potentials of Purkinje fibers. At 3 mg/kg, EN-313 significantly decreased maximum upstroke velocity of phase 0 depolarization and action potential duration. In conscious dogs, EN-313 (1-3 mg/kg i.v.; 10-20 mg/kg p.o.) reduced arrhythmias that occured larger than or equal to 24 h after coronary artery ligation. No excessive changes in electrocardiographic parameters were observed following EN-313. These studies demonstrate that EN-313 suppresses ventricular arrhythmias in doses which have little effect on cellular electrophysiologic properties of normal Purkinje fibers and suggest that EN-313 should be useful in treating cardiac arrhythmias arising as a result of coronary occlusion.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008026:Ligation; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology; D010640:Phenothiazines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology; D013997:Time Factors
D009025:Morpholines; D010640:Phenothiazines; D011802:Quinidine; D004837:Epinephrine