ELECTROPHYSIOLOGICAL MECHANISMS IN A CANINE MODEL OF ERYTHROMYCIN-ASSOCIATED LONG QT SYNDROME

Article

关键词: CARDIAC PURKINJE-FIBERS;    DEPENDENT EARLY AFTERDEPOLARIZATIONS;    ACTION-POTENTIAL PROLONGATION;    MONOPHASIC ACTION-POTENTIALS;    TRANSIENT OUTWARD CURRENT;    TRIGGERED ACTIVITY;    VENTRICULAR-TACHYCARDIA;    DELAYED AFTERDEPOLARIZATIONS;    WENCKEBACH PHENOMENON;    ELECTRICAL ALTERNANS;   

DOI  :  10.1161/01.CIR.88.4.1832

来源: SCIE

【 摘 要 】

Background. Erythromycin is known to prolong ventricular repolarization and has been associated with the occurrence of torsades de pointes. In this study, we have investigated potential mechanisms in vivo and in vitro for induction of an acquired long QT syndrome by erythromycin. Methods and Results. Ventricular electrograms and endocardial monophasic action potentials were recorded in anesthetized open-chest dogs before and after administration of 40 to 120 mg/kg of erythromycin lactobionate. Conventional microelectrode techniques were used to record transmembrane action potentials in isolated dog Purkinje fibers and papillary muscles. Erythromycin at concentrations >20 mg/L prolonged action potential duration. At higher concentrations (100 to 200 mg/L), erythromycin induced phase 2 and phase 3 early afterdepolarizations (EADs) both in vivo and in vitro. The effects of erythromycin on repolarization were more marked in Purkinje fibers than in papillary muscle. Pretreatment of Purkinje fibers with erythromycin antagonized the effects of dofetilide, a selective delayed-rectifier potassium channel (I(K)) blocker. Pretreatment with prazosin or tetrodotoxin had no effect on erythromycin-induced changes in action potential duration. Conclusions. These pharmacological studies suggest that erythromycin prolongs repolarization to a large extent by block of I(K). In turn, prolongation of action potential duration resulting from erythromycin's actions on I(K) may promote the development of EADs. The induction of ventricular arrhythmias observed clinically after exposure to erythromycin may be related to the development of EADs. The rarity of occurrence of ventricular arrhythmias suggests that other predisposing factors contribute to the acquired long QT syndrome associated with erythromycin.

【 授权许可】

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