Effects of Diphenylhydantoin on Excitability and Automaticity in the Canine Heart

Abstract

Studies were performed on the dog heart in situ to determine the effects of diphenylhydantoin (DPH) on excitability and automaticity. DPH decreased automaticity in the His-Purkinje system, evidenced by an increase in the ventricular escape time both during vagal stimulation in intact dogs and after ventricular overdrive in dogs with heart block. The spontaneous ventricular rate of dogs with heart block was unaffected by doses up to 20 mg/kg. DPH had no significant effect on either atrial or ventricular diastolic threshold when this variable was tested with bipolar stimuli or with stigmatic anodal or cathodal stimuli. The effective refractory period of atrial and particularly of ventricular muscle was shortened by DPH (10 mg/kg); a leftward shift in the strength-interval curve occurred consistently. Multiple response threshold and fibrillation thresholds were elevated by DPH in both the ventricle and atrium (20 of 24 experiments). In anesthetized dogs, intraventricular conduction velocity increased minimally after DPH administration. DPH increased transmembrane threshold voltage and reduced the current required to stimulate isolated Purkinje fibers. The commercial solvent used clinically as a diluent for DPH was found to increase diastolic threshold and prolong the effective refractory period.