Suppression of erythromycin-induced early afterdepolarizations and torsade de pointes ventricular tachycardia by mexiletine

T. Fazekas, I. Krassoi, C. Lengyel, A. Varró, J. Papp

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 FADs (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.

Original languageEnglish
Pages (from-to)147-150
Number of pages4
JournalPACE - Pacing and Clinical Electrophysiology
Volume21
Issue number1 II SUPPL.
DOIs
Publication statusPublished - 1998

Fingerprint

Mexiletine
Torsades de Pointes
Erythromycin
Ventricular Tachycardia
Action Potentials
Purkinje Fibers
Flavin-Adenine Dinucleotide
Tetrodotoxin
Microelectrodes
Pharmaceutical Preparations
Canidae

Keywords

  • Early afterdepolarizations
  • Erythromycin
  • Mexiletine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "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 FADs (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.",
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AU - Krassoi, I.

AU - Lengyel, C.

AU - Varró, A.

AU - Papp, J.

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