SUPPRESSION OF ERYTHROMYCIN-INDUCED EARLY AFTERDEPOLARIZATIONS AND TORSADE-DE-POINTES VENTRICULAR-TACHYCARDIA BY MEXILETINE

Erythromycin is a selective I-Kr-blocking, action potential duration? (APD)-prolonging drug, which may induce early afterdepolarizations (EA Ds) and torsade de pointes ventricular tachycardia. The successful ter mination of an erythromycin-induced clinical? torsades de pointes by t he authors, with mexiletine prompted them to investigate in vitro whet her erythromycin is able to induce EADs in Purkinje fibers and if so, whether EADs are suppressible or not by mexiletine. Electrically stimu lated canine Purkinje fibers (n=9) were superfused with erythromycin ( 200 mg/l) and action potentials were recorded by an intracellular micr oelectrode technique. Erythromycin, cin induced a pronounced prolongat ion? of APD and the appearance of EADs in all Purkinje preparations (9 /9). After the addition of mexiletine (IO mM), a marked shortening of APD and the disappearance of EADs (7/9) were observed. Mexiletine, an inhibitor of the tetrodotoxin-sensitive window Na+-current, may preven t IKr-blocking drug-induced torsade de pointes ventricular tachycardia by abolishing APD prolongation? and EADs.