Effects of therapeutic concentrations of diphenylhydantoin on transmembrane potentials of normal and depressed Purkinje fibers.
Standard intracellular microelectrode techniques were used to study canine Purkinje fibers (PF) which had been superfused with blood or Tyrode's solution to determine the cardiac cellular electrophysiologic changes induced by antiarrhythmic concentrations of diphenylhydantoin (DPH). Some PF were normal whereas others were depressed by stretch, exposure to ouabain (125 mug/1) or superfusion with a solution in which all Na+ was replaced by tetraethylammonium. For normal fibers, therapeutic concentrations of DPH (DPH) induced slight decreases in action potential (AP) amplitude, maximum upstroke velocity of phase O (Vmax) and membrane responsiveness and somewhat greater decreases in AP duration. For fibers moderately depressed by ouabain or stretch, with reduced AP amplitude, maximum diastolic potential and Vmax, therapeutic [DPH] increased these variables. Fibers markedly depressed by Na-free solution or stretch developed slow response AP. The amplitude and Vmax of the AP were decreased by therapeutic [DPH]. Therapeutic [DPH] also suppressed automaticity and ouabain-induced delayed afterdepolarizations. Our studies suggest that the slight depression of normal PF AP characteristics induced by therapeutic [DPH] probably is of little significance with respect to antiarrhythmic effect. In contrast, both the improvement of AP characteristics of moderately depressed fibers and further depression of severely depressed fibers caused by [DPH] might modify arrhythmias. Effects of DPH on automaticity and delayed afterdepolarizations also would contribute to its antiarrhythmic effect.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D010672:Phenytoin / Q000494:pharmacology*; D010949:Plasma; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012996:Solutions; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D012996:Solutions; D013757:Tetraethylammonium Compounds; D010042:Ouabain; D010672:Phenytoin