Actions of Diphenylhydantoin on the Electrical Properties of Isolated Rabbit and Canine Atria

The effects of diphenylhydantoin (DPH), 10 -8 to 10 -4 M, were studied on the various types of cells in the isolated right atrial preparation and on the specialized cells of Bachmann's bundle in atrial preparations obtained from puppies. High concentrations of DPH (10 -4 M) slowed sinoatrial rate but lower concentrations had little effect. These chronotropic effects of DPH were direct. DPH in concentrations above 10 -5 M decreased the slope of phase 4 depolarization in cells in the sinoatrial node and venous automatic tissue. DPH in concentrations of 10 -8 to 10 -6 M had no effect on transmembrane action potentials recorded from any cell studied; concentrations of 10 -4 M, however, prolonged the terminal phase of repolarization. High concentrations (10 -4 M) also prolonged the effective refractory period of Bachmann's bundle and ordinary atrial and perinodal fibers by an average of 10%. DPH markedly increased the dv/dt of phase 0 of the action potential and membrane responsiveness of ordinary atrial and specialized Bachmann's bundle fibers under control conditions and produced more striking increases when these two variables had been decreased by ouabain. DPH was also proved capable of reversing ouabain-induced sinoatrial block. This unique ability of DPH to enhance membrane responsiveness and to improve conduction in the absence of significant effects on the effective refractory period and automaticity of atrial cells suggests that this may be the sole mechanism of its antiarrhythmic action.