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The effects of diphenylhydantoin (DPH) were studied on isolated, perfused Purkinje fibers over a range of concentrations from 10 -8 to 10 -4 M . The time course of repolarization of the transmembrane action potential shortened due to abbreviation of all phases of repolarization. The effective refractory period also shortened during exposure to DPH, but to a lesser extent than the action potential. As a result the earliest effective test stimulus elicited action potentials with greater amplitude and dv/dt of phase 0 than under control conditions. In driven fibers with normal action potentials, DPH had little effect on the amplitude or rate of rise (dv/dt) of phase 0 of the action potential. In driven fibers which were partially depolarized, or those with low dv/dt of phase 0 despite normal resting potentials, DPH caused an increase in the rate of rise of phase 0 of the action potential. DPH caused a decrease in the firing rate of normal automatic fibers by decreasing the slope of phase 4 depolarization. In automatic fibers which showed generalized diastolic depolarization and decreased maximum diastolic potential, DPH caused an increase in the latter as well as a decrease in the slope of phase 4 depolarization.
Bigger et al. (Thu,) studied this question.