Antiarrhythmic actions of clemizole as pharmacologic evidence for a circus movement mechanism in atrial flutter

Summary

The antihistaminic clemizole was studied as an antiarrhythmic in a preparation in which two arrhythmias of different nature and mechanism were produced in the right atrium of anesthetized dogs. One of the arrhythmias was a circus movement flutter induced by the method of Rosenblueth and García Ramos; the other, an ectopic focus induced by local application of aconitine in the auricular appendage, electrically isolated from the rest of the atrium. Clemizole selectively converted the flutter to sinus rhythm with little action on the coexistent aconitine dysrhythmia. It did not modify arterial pressure. In effective doses the wave length of the impulse was increased by prolongation of the refractory period without significant reduction in conduction velocity. Similarly, in subendocardial cells of isolated rat atria, clemizole in appropriate concentrations retards repolarization with little effect on the rate of depolarization. These results afford pharmacological evidence for the existence of atrial circus movement arrhythmias which can respond to prolongation of the refractory period unaccompanied by effects on other properties of the tissue. Other arrhythmias, self-sustained by the discharge of an ectopic focus, such as the tachysystole produced by aconitine, are not suppressed by similar increase in the refractory period.