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d-索他洛尔对从正常犬心脏或梗死后10至14天犬心脏分离的心内膜下浦肯野心肌细胞的不同作用:细胞外钾浓度的作用

Differential effects of d-sotalol on subendocardial Purkinje myocytes isolated from normal or 10 to 14 days postinfarction canine hearts: role of extracellular potassium concentration.

作者信息

Marschang H, Schöls W, Karolyi L, Beyer T, Kübler W, Brachmann J

机构信息

Department of Cardiology, University of Heidelberg, Germany.

出版信息

J Cardiovasc Pharmacol. 1998 Aug;32(2):274-83. doi: 10.1097/00005344-199808000-00015.

Abstract

Electrophysiologic properties of surviving Purkinje cardiomyocytes in the late postmyocardial-infarction phase are not well established. By using standard microelectrode techniques, we evaluated the effects of the class III agent d-sotalol on action potential parameters of single Purkinje cardiomyocytes isolated from normal canine hearts or those 10-14 days after infarction. Measurements were obtained at 2.5, 3.5, and 6 mM extracellular potassium concentrations. Action-potential parameters recorded at baseline did not differ significantly between normal and infarct-surviving Purkinje cardiomyocytes. At 3.5 and 6 mM extracellular potassium concentrations, surviving Purkinje cells appeared to be more sensitive to the effects of d-sotalol than normal Purkinje cells. In contrast, at 2.5 mM extracellular potassium concentration, the differential responses of normal and infarct-surviving Purkinje cells to d-sotalol was abolished. Reverse rate dependence was more prominent in normal than in postinfarction Purkinje cells, independent of the extracellular potassium concentration studied. The previously described enhanced sensitivity of subacutely infarcted tissue to class III agents seems to persist on a cellular level 10-14 days after myocardial infarction, even after full normalization of baseline action-potential parameters. Differential membrane-regulation mechanisms, dependent on the extracellular potassium concentrations, may account for the increased susceptibility to antiarrhythmia agents in the late postinfarction phase.

摘要

心肌梗死后晚期存活的浦肯野心肌细胞的电生理特性尚未完全明确。通过使用标准微电极技术,我们评估了Ⅲ类药物d - 索他洛尔对从正常犬心脏或梗死后10 - 14天的心脏中分离出的单个浦肯野心肌细胞动作电位参数的影响。在细胞外钾浓度为2.5、3.5和6 mM时进行测量。正常和梗死后存活的浦肯野心肌细胞在基线时记录的动作电位参数没有显著差异。在细胞外钾浓度为3.5和6 mM时,存活的浦肯野细胞似乎比正常浦肯野细胞对d - 索他洛尔的作用更敏感。相反,在细胞外钾浓度为2.5 mM时,正常和梗死后存活的浦肯野细胞对d - 索他洛尔的差异反应消失。反向频率依赖性在正常浦肯野细胞中比梗死后浦肯野细胞更显著,与所研究的细胞外钾浓度无关。先前描述的亚急性梗死组织对Ⅲ类药物的敏感性增强在心肌梗死后10 - 14天似乎在细胞水平上仍然存在,即使基线动作电位参数完全恢复正常。依赖于细胞外钾浓度的不同膜调节机制可能解释了梗死后晚期对抗心律失常药物易感性的增加。

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