ERYTHROMYCIN BLOCKS THE RAPID COMPONENT OF THE DELAYED RECTIFIER POTASSIUM CURRENT AND LENGTHENS REPOLARIZATION OF GUINEA-PIG VENTRICULAR MYOCYTES

被引：73

作者：

DALEAU, P

LESSARD, E

GROLEAU, MF

TURGEON, J

机构：

[1] LAVAL HOSP,QUEBEC HEART INST,RES CTR,ST FOY,PQ G1V 4G5,CANADA

[2] UNIV LAVAL,SCH PHARM,ST FOY,PQ G1K 7P4,CANADA

来源：

CIRCULATION | 1995年 / 91卷 / 12期

关键词：

ACTION POTENTIALS; POTASSIUM; TORSADE DE POINTES; CALCIUM CHANNELS;

D O I：

10.1161/01.CIR.91.12.3010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Administration of erythromycin to humans has been associated with lengthening of cardiac repolarization and even proarrhythmia. The objectives of our study were to describe effects of erythromycin on repolarization of isolated hearts and to determine effects of the drug on major K+ currents involved in cardiac repolarization. Methods and Results A first set of experiments was conducted in isolated, buffer-perfused guinea pig hearts electrically stimulated at a basic cycle length of 250 ms. In this model, erythromycin 10(-4) mol/L increased monophasic action potential duration measured at 90% repolarization (MAPD(90)) by 40 +/- 7 ms. Increase in MAPD(90) was reproducibly observed in seven hearts studied. To study the mechanism of these effects on cardiac repolarization, a second set of experiments was performed in isolated guinea pig ventricular myocytes using the whole cell configuration of the patch-clamp technique. In these cells, erythromycin 10(-4) mol/L decreased by about 40% (P<.05 versus baseline) the time-dependent outward K+ current elicited by short depolarizations (250 ms) to low depolarizing voltages (-20 to 0 mV). In contrast, the drug was without significant effects on the time-dependent K+ current elicited by long pulses (5000 ms) to high depolarizing voltages (+10 to +50 mV), on the time-independent background current (mostly I-K1), and on the slow inward calcium current. Conclusions The outward time-dependent K+ current blocked by erythromycin in isolated guinea pig ventricular myocytes had characteristics similar to those described for I-Kr. Selective block of this component of I-K gives an explanation for the effects of erythromycin on cardiac repolarization. These effects were observed at clinically relevant concentrations reached after intravenous administration of the drug and warn for potential interactions with other action potential-lengthening drugs.

引用

页码：3010 / 3016

页数：7

共 24 条

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