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D-和DL-索他洛尔对豚鼠窦房结、心房和心室以及人心房的细胞电生理效应:不同组织敏感性

Cellular electrophysiological effects of D- and DL-sotalol in guinea-pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity.

作者信息

Campbell T J

出版信息

Br J Pharmacol. 1987 Mar;90(3):593-9. doi: 10.1111/j.1476-5381.1987.tb11210.x.

Abstract

The effects of racemic DL-sotalol and D-sotalol on guinea-pig sino-atrial node, atrium and ventricle and on human atrium were studied using standard microelectrode techniques. Both compounds increased spontaneous sinus node cycle length largely by prolonging the repolarization phase of the action potentials. This effect was attributed to blockade of outward potassium current. Ventricular action potential duration was similarly prolonged by DL-sotalol at concentrations of 5-50 microM. DL-Sotalol 1-50 microM had no effect on guinea-pig atrial action potential duration and D-sotalol produced minor prolongation only at the highest concentration (50 microM). Human atrial action potentials were, however, significantly prolonged by both DL- and D-sotalol 10 microM. This indicates differential sensitivities to sotalol for human and guinea-pig atrium and explains the ability of sotalol to prolong atrial monophasic action potential duration in clinical studies.

摘要

使用标准微电极技术研究了消旋 DL-索他洛尔和 D-索他洛尔对豚鼠窦房结、心房和心室以及对人心房的作用。两种化合物主要通过延长动作电位的复极化阶段来增加窦性自发周期长度。这种作用归因于外向钾电流的阻断。在 5-50 μM 的浓度下,DL-索他洛尔同样延长了心室动作电位持续时间。1-50 μM 的 DL-索他洛尔对豚鼠心房动作电位持续时间没有影响,而 D-索他洛尔仅在最高浓度(50 μM)时产生轻微延长。然而,10 μM 的 DL-索他洛尔和 D-索他洛尔均显著延长了人心房动作电位。这表明人和豚鼠心房对索他洛尔的敏感性不同,并解释了索他洛尔在临床研究中延长心房单相动作电位持续时间的能力。

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本文引用的文献

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Sotalol and prolonged Q-Tc interval.索他洛尔与Q-Tc间期延长。
Lancet. 1981 Aug 22;2(8243):426. doi: 10.1016/s0140-6736(81)90876-x.

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