由d，l-索他洛尔和氯非铵产生的早期后去极化。

Early afterdepolarizations produced by d,l-sotalol and clofilium.

作者信息

Patterson E, Scherlag B J, Lazzara R

机构信息

Department of Pharmacology, College of Medicine, University of Oklahoma Health, Sciences Center, Oklahoma City, USA.

出版信息

J Cardiovasc Electrophysiol. 1997 Jun;8(6):667-78. doi: 10.1111/j.1540-8167.1997.tb01830.x.

DOI:10.1111/j.1540-8167.1997.tb01830.x

PMID:9209968

Abstract

INTRODUCTION

The roles for L-type calcium current and Na-Ca exchange in early afterdepolarizations (EADs) attending d,l-sotalol and clofilium were examined in canine Purkinje fibers and in enzymatically dispersed myocytes from canine subepicardium.

METHODS AND RESULTS

Spontaneous EADs were compared to EAD formation potentiated by stimulation of Na-Ca exchange and facilitation of ICa-L (Bay K8644). Bay K8644 (10(-8) M) and stimulation of Na-Ca exchange potentiated bradycardia-dependent EADs. Stimulation of Na-Ca exchange in Purkinje fibers pretreated with d,l-sotalol (10(-5) M) and clofilium (10(-7) M) induced EADs at takeoff potentials negative (-63 +/- 4 and -62 +/- 4 mV, respectively) to EADs potentiated by Bay K8644 (10(-8) M) (-33 +/- 2 and -34 +/- 2 mV, respectively, P < 0.05), or EADs induced by Bay K8644 alone (10(-6) M) (-31 +/- 5 mV). In myocytes, Bay K8644 (10(-8) M) potentiated EADs in d,l-sotalol- (10(-6) to 10(-4) M) or clofilium-treated (10(-9) to 10(-7) M) cells at reduced potentials (-10 +/- 3 and -10 +/- 4 mV, respectively) compared to EADs elicited by clofilium or d,l-sotalol alone (-25 +/- 3 and -24 +/- 3 mV, respectively), or stimulation of Na-Ca exchange in the presence of d,l-sotalol or clofilium (-26 +/- 4 and -26 +/- 4 mV, respectively). Spontaneous EADs or EADs elicited by stimulation of Na-Ca exchange coincident with drug treatment were suppressed by increasing Ca02+ but were not suppressed by nifedipine (10(-7) M).

CONCLUSION

EADs elicited by d,l-sotalol and clofilium in canine Purkinje tissue and epicardial myocytes are dependent upon Na-Ca exchange rather than ICa-L "window current."

摘要

引言

在犬浦肯野纤维和犬心外膜酶分散的心肌细胞中，研究了L型钙电流和钠钙交换在d，l - 索他洛尔和氯非铵引发的早期后去极化（EADs）中的作用。

方法与结果

将自发性EADs与通过刺激钠钙交换和促进L型钙电流（Bay K8644）增强的EADs形成进行比较。Bay K8644（10^(-8) M）和钠钙交换刺激增强了心动过缓依赖性EADs。在用d，l - 索他洛尔（10^(-5) M）和氯非铵（10^(-7) M）预处理的浦肯野纤维中，刺激钠钙交换在去极化电位为负（分别为-63±4和-62±4 mV）时诱导出EADs，而Bay K8644（10^(-8) M）增强的EADs的去极化电位为（分别为-33±2和-34±2 mV，P < 0.05），或单独使用Bay K8644（10^(-6) M）诱导的EADs（-31±5 mV）。在心肌细胞中，与单独使用氯非铵或d，l - 索他洛尔（分别为-25±3和-24±3 mV）或在d，l - 索他洛尔或氯非铵存在下刺激钠钙交换（分别为-26±4和-26±4 mV）相比，Bay K8644（10^(-8) M）在d，l - 索他洛尔（10^(-6)至10^(-4) M）或氯非铵处理（10^(-9)至10^(-7) M）的细胞中在降低的电位（分别为-10±3和-10±4 mV）下增强了EADs。自发性EADs或与药物治疗同时发生的钠钙交换刺激引发的EADs通过增加Ca02 +被抑制，但不被硝苯地平（10^(-7) M）抑制。