EFFECTS OF PILSICAINIDE ON THE ATRIAL-FIBRILLATION THRESHOLD IN GUINEA-PIG ATRIA - A COMPARATIVE-STUDY WITH DISOPYRAMIDE, LIDOCAINE AND FLECAINIDE

The effects of pilsicainide, a new class Ic antiarrhythmic agent, on t he atrial fibrillation threshold (AFT), the atrial effective refractor y period (ERP), and the interatrial conduction time (ACT) in Langendor ff-perfused guinea pig hearts were investigated. These effects were co mpared with those of disopyramide, lidocaine and flecainide. Whole gui nea pig heart was perfused with Tyrode's solution containing acetylcho line (3x10(-7) M). Three indices were measured before and after the ad ministration of the test drugs using right atrial extrastimulus and hi gh frequency stimulation. Pilsicainide, disopyramide and flecainide (g reater-than-or-equal-to 10(-6) M) all significantly increased the AFT. Both pilsicainide and flecainide (greater-than-or-equal-to 3x10(-6) M ) significantly prolonged the ERP, but this prolongation was less pron ounced than that observed with disopyramide. The ACT was significantly prolonged with pilsicainide (greater-than-or-equal-to 10(-6) M), and this prolongation was greater than that observed with disopyramide but less than that with flecainide. Lidocaine had no effects on any of th e indices measured. In conclusion, pilsicainide had a preventive effec t on the atrial fibrillation induced by a combination of acetylcholine and high frequency stimulation in guinea pig hearts, by increasing th e atrial ERP and slowing the interatrial conduction. These effects may explain, in part, the clinical effectiveness of this drug on paroxysm al atrial fibrillation.