Electrophysiologic effects of disopyramide phosphate on reentrant ventricular arrhythmia in conscious dogs after myocardial infarction.
The electrophysiologic actions of disopyramide phosphate on reentrant ventricular tachycardia induced by premature ventricular stimuli were evaluated in conscious dogs 2 to 4 days after myocardial infarction. Disopyramide was administered as a series of intravenous infusions to obtain successive steady state plasma disopyramide concentrations of 1.02 +/- 0.02, 2.05 +/- 0.08, 3.94 +/- 0.09 and 7.69 +/- +/- 0.18 micrograms/ml (mean values +/- standard error of the mean). Disopyramide plasma concentrations of 1.02 +/- 0.02 micrograms/ml produced an increase in the rate and duration of ventricular tachycardia as well as in the interval during which premature ventricular stimuli produced ventricular tachycardia. The effective refractory period of normal myocardium was decreased and conduction (activation time) was improved in ischemic myocardium. Increasing steady state plasma disopyramide concentrations slowed the rate of ventricular tachycardia without decreasing its duration. Slowing of the rate of tachycardia occurred simultaneously with a depression of conduction in normal and ischemic myocardium and an increase in ventricular refractoriness. Induction of ventricular tachycardia was prevented only at steady state plasma disopyramide concentrations of 7.69 +/- 0.18 micrograms/ml. The results of this study suggest that subtherapeutic plasma concentrations of disopyramide may facilitate the development of reentrant ventricular arrhythmia in the electrically unstable heart. Ventricular tachycardia or fibrillation, or both, may be prevented only by plasma disopyramide concentrations that are in excess of the normal therapeutic range of 2 to 4 micrograms/ml.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004206:Disopyramide / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D011188:Potassium / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D013610:Tachycardia / Q000209:etiology
D011725:Pyridines; D004206:Disopyramide; D011188:Potassium