title: Electrophysiologic effects of disopyramide studied in a hypoxic canine Purkinje fiber model.
abstract: Under normal (95% + 5% CO2) and hypoxic (95% N2 + 5% CO2) perfusions, electrophysiologic effects of disopyramide phosphate (5 microgram/ml) on canine Purkinje fibers were studied using microelectrode techniques. In the presence of normal oxygenation, disopyramide decreased the action potential amplitude and maximal rate of phase 0 depolarization, and lowered the level of plateau. The action potential duration at 80% of repolarization was prolonged in fibers initially having shorter durations, whereas it was shortened in fibers with longer durations, making the repolarization process more uniform. Addition of disopyramide under hypoxia similarly decreased the amplitude and upstroke velocity of action potential, and tended to reverse hypoxia-induced shortening of the refractory period. The maximal diastolic potential was altered by neither hypoxia nor disopyramide alone, but was significantly decreased by the combination of these two factors. Disopyramide prolonged the effective refractory period more than the action potential duration. From these results, antiarrhythmic effects of disopyramide under hypoxia appear to depend on (1) depressed conduction and resultant conversion of unidirectional block to bidirectional block abolishing reentry, and (2) decreased vulnerability due to decreased inhomogeneity of repolarization. Usefulness of this experimental model in studying electrophysiologic action of antiarrhythmic agents in ischemic hearts is also suggested.
mesh_terms: D000818:Animals; D003971:Diastole / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D008954:Models, Biological; D010101:Oxygen Consumption; D010477:Perfusion; D011690:Purkinje Fibers / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D011725:Pyridines; D004206:Disopyramide