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

Abstract

The effects of diphenylhydantoin (DPH), 1(H to 1(HM, 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 (1(HM) slowed sinoatrial rate but lower concentrations had little effect. These chronotropic effects of DPH were direct. DPH in concentrations above 10~5M decreased the slope of phase 4 depolarization in cells in the sinoatrial node and venous automatic tissue. DPH in concentrations of 1C H to ICHM had no effect on transmembrane action potentials recorded from any cell studied; concentrations of ICMM, however, prolonged the terminal phase of repolarization. High concentrations (ICHM) 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.ADDITIONAL KEY WORDS automaticity transmembrane potentials effective refractory period antiarrhythmic activity reactivation membrane responsiveness acetylcholine atropine catecholamines• Recent reports indicate that diphenylhydantoin sodium (DPH) is effective in abolishing many ventricular arrhythmias (1-11). Among the atrial arrhythmias, only supraventricular tachycardia, paroxysmal atrial tachycardia, and digitalis-induced atrial arrhythmias usually respond to DPH therapy From the

Effect of lidocaine on the electrophysiological properties of ventricular muscle and Purkinje fibers

“…Temperature was maintained at 36 ±10C. The composition of the Tyrode solution and the techniques used for stimulating and recording have been described previously (19,22 In most experiments, the preparations were arranged as shown in Fig. 1.…”

“…It is interesting that the antiarrhythmic lidocaine plasma concentration of 2-5 Ag/ml in man (6) is so similar to the in vitro concentration thought to produce comparable effects. We recognize the fact that many difficulties are encountered in attempts to relate in vivo plasma concentrations to the concentration of drugs perfusing isolated preparations of cardiac tissue (22). The similarity between the effective in vitro and in vivo concentrations may be due, in part, to the fact that lidocaine, unlike procaine amide or quinidine, is not significantly bound to plasma proteins (30)(31)(32) and diffuses readily into the tissues (25,30).…”

Diphenylhydantoin Inhibition of Sodium Conductance in Squid Giant Axon

“…In peripheral nerve this compound has, nonspecially, been considered to be a membrane "stabilizer" because it prevented or interrupted repetitive electrical activity induced by various means (5)(6)(7). However, a decrease in the maximum rate of rise of the action potential in isolated rat atrial fibers indirectly suggests that this drug can impair the sodium mechanism involved in the genesis of the action potential (8,9). In this report, we describe ion-specific effects of diphenylhydantoin in the squid giant axon.…”

“…The toxins and diphenylhydantoin alter #Na without modifying the relevant time constants, and it appears that both types of drug do not significantly affect the potassium currents. The effect of diphenylhydantoin on 9Na accounts for its ability to block conducted action potentials (9), offers a mechanism for its decrease in the maximum rate of rise of the action potential seen in isolated myocardium (6), accounts for its stabilizing effects in peripheral nerve (7)(8)(9), and is the first clear description of its effects on ion-specific electrophysiological mechanisms. It is attractive to speculate that the effect of diphenylhydantoin on #Na is related to its antiarrhythmic and anticonvulsant properties.…”

Effect of lidocaine hydrochloride on membrane conductance in mammalian cardiac purkinje fibers

“…The heart was rapidly removed and false tendon (Purkinje fiber) preparations were selected for study. Our standard techniques for stimulating and recording have been previously described (5,6). When current-voltage relationships were studied, methods similar to those of Weidmann (7) and Hall, Hutter, and Nobel (8) were employed.…”