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Suppression of Erythromycin‐induced Early Afterdepolarizations and Torsade de Pointes Ventricular Tachycardia by Mexiletine
Author(s) -
FAZEKAS TAMÁS,
KRASSÓI IRÉN,
LENGYEL CSABA,
VARRÓ ANDRÁS,
PAPP JULIUS GY
Publication year - 1998
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/j.1540-8159.1998.tb01078.x
Subject(s) - medicine , mexiletine , afterdepolarization , ventricular tachycardia , cardiology , torsades de pointes , long qt syndrome , anesthesia , erythromycin , qt interval , electrophysiology , repolarization , antibiotics , microbiology and biotechnology , biology
Erythromycin is a selective I Kr ‐blocking, action potential duration (APD)‐prolonging drug, which may induce early afterdepolarizations (EADs) and torsade de pointes ventricular tachycardia. The successful termination of an erythromycin‐induced clinical torsades de pointes by the authors with mexiletine prompted them to investigate in vitro whether erythromycin is able to induce EADs in Purkinje fibers and, if so, whether EADs are suppressible or not by mexiletine. Electrically stimulated canine Purkinje fibers (n=9) were superfused with erythromycin (200 mg/l) and action potentials were recorded by an intracellular microelectrode technique. Erythromycin induced a pronounced prolongation of APD and the appearance of EADs in all Purkinje preparations (9/9). After the addition of mexiletine (10 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 prevent IKr‐blocking drug‐induced torsade de pointes ventricular tachycardia by abolishing APD prolongation and EADs.