[Experimental anti-arrhythmic action of perhexiline]

The antiarrhythmic action of Perhexiline phosphate, in doses of 3 and 6 mg/kg on various experimental cardiac arrhytmias and on the physiological properties of the atrial myocardium has been studied in the anesthetized dog. Its action in concentrations of 3 and 6 mcg/ml on the transmembrane action potentials in isolated Purkinje fibers has also been analyzed. The activity of perhexiline is comparatively greater in the circus movement atrial flutter and in the arrhythmias caused by ouabain and by barium chloride intoxication than in the atrial tachysystolia caused by the local application of aconitine. Perhexiline prolongs the wave length (refractory period times conduction velocity) of the atrial impulse and depresses atrial excitability. These effects may explain its action on experimental atrial flutter. In isolated Purkinje fibers, perhexiline reduces the maximum velocity of depolarization, the overshoot, the amplitude of the action potential and its duration, measured at 50% of its repolarization phase. The relation of these electrophysiological effects of perhexiline to the genesis of each type of arrhythmia may explain its different type of activity in the experimental models studied.