Electrophysiologic Effects of Diltiazem, a New Slow Channel Inhibitor, on Canine Cardiac Fibers

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Abstract
The effect of diltiazem hydrochloride (CRD-401), a coronary vasodilator, was investigated in isolated perfused canine ventricular muscles and Purkinje fibers using microelectrodes. The drug at a concentration of 1 .mu.g/ml lowered the level of action potential plateau and shortened the duration in both ventricular and Purkinje fibers without change in maximum rate of rise (.ovrhdot.Vmax) or resting potential. Contractile tension of ventricular muscle was markedly decreased with shortening of plateau. With higher drug concentration (5 .mu.g/ml), .ovrhdot.Vmax in both ventricular muscle and Purkinje fiber decreased about 20% without change in resting potential, and the effect on repolarization became more marked. The drug blocked spontaneous firing which appeared in depolarized Purkinje fibers and abolished the automaticity elicited in electrically depolarized ventricular muscles. Input resistance of ventricular muscle, measured by small, hyperpolarizing short pulses, was not changed appreciably by the drug; suggesting no change in K conductance. The drug appears to be a slow channel inhibitor, and its clinical implication is discussed in terms of antiarrhythmic activity.