Effects of Perhexiline Maleate on the Refractory Periods of Isolated Atrial Muscle and Atrioventricular Node of the Rabbit

The electrophysiologic effects of perhexiline maleate were studied with glass microelectrodes in three types of isolated rabbit heart preparations: (a) sinoatrial node preparation; (b) left atrial free-wall preparation; and (c) atrioventricular node preparation. The spontaneous firing rate of the sinoatrial node was decreased by 10-15% at a concentration of 10(-5) g/ml. The sinus node recovery time after atrial overdrive was prolonged by about 50%. The effective refractory period of the left atrial free wall showed concentration-dependent prolongation at concentrations above 10(-7) g/ml. Although this period was shortened after washing with perhexiline-free Tyrode solution, it did not return to the control lever. The effective refractory period of the right atrium was prolonged by 15% at a concentration of 10(-5) g/ml, but the functional refractory period did not change. The conduction time, effective refractory period, and functional refractory period of the atrioventricular node were significantly increased. Previous reports had claimed that perhexiline had pharmacologic effects on Purkinje fibers and ventricular myocardium at lower concentrations than on the atrium, but we found significant actions on the atrium and the atrioventricular node in therapeutic concentrations.