Beta-adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol.
Beta-adrenergic blocking property of dl-sotalol maintains class III efficacy in guinea pig ventricular muscle after isoproterenol.
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dl-索他洛尔的 β-肾上腺素能阻滞特性在异丙肾上腺素治疗后对豚鼠心室肌维持 III 级功效。
DOI：
10.1161/01.cir.91.2.262
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发表时间：
1995
期刊：
影响因子：
37.8
通讯作者：
Maylie,JG
中科院分区：
文献类型：
--
作者：
Groh,WJ;Gibson,KJ;McAnulty,JH;Maylie,JG
背景儿茶酚胺拮抗几种III类抗心律失常药物的疗效。为了确定dl-索他洛尔固有的β-肾上腺素能阻断特性在维持高儿茶酚胺状态下的Ⅲ类效应中的作用，我们比较了dl-索他洛尔和无明显β-肾上腺素能阻断作用的d-索他洛尔在注射异丙肾上腺素前后的电生理特性。方法与结果在200~2000ms的刺激周期中，dl-索他洛尔和dl-索他洛尔10−4mol/L可延长豚鼠乳头肌90%复极的动作电位时程。APD90ford-sotalol和dl-sotalol较对照组分别增加10.9±2.5至23.7±4.8ms和27.9±4.0至39.0±5.6 ms。在加入异丙肾上腺素10−6mol/L时，加入索他洛尔而不加索他洛尔的乳头肌APD90缩短至对照组：−31.2±3.5至−18.3±4.8ms及10.5±3.6至33.3±7.8ms，P<0.003。采用全细胞膜片钳技术对单个豚鼠心室肌细胞进行研究。在钙通道阻断和钠通道失活后，测量300ms脉冲至20 mV时的时间依赖性外向电流(Iout)和总外向电流(Itot)以及35 mV的尾电流(ITail)。经d-索他洛尔和dl-索他洛尔10−/L灌流的心肌细胞的Iout、Iail和Itot均减少：Iout，−36.1±4.1%，−40.5±3.3%，Iail，−59.3±4.6%，−62.2±11.1%，Itot，−27.3±4.3%，−50.0±11.8%。在加入异丙肾上腺素10−6mol/L时，索他洛尔和索他洛尔对心肌细胞Iout和Itt的影响较大：Iout，100.3±20.6%，11.3±7.6%，P=0.002；Itot，86.8±39.2%，−41.1±20.9%，P=0.01。加入异丙肾上腺素后，d-索他洛尔和l-索他洛尔使心肌细胞−增加更多，但差异无统计学意义(APD9.1±13.5%，−28.0±9.0%)。结论dl-索他洛尔的β-肾上腺素能阻断作用维持了异丙肾上腺素对豚鼠心肌细胞动作电位时程的延长和复极化外向电流的阻断。将这些数据外推到临床环境中可以解释dl-索他洛尔在减少室性心律失常复发方面的有效性。
BackgroundCatecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic β-adrenergic blocking property ofdl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties ofdl-sotalol with those ofd-sotalol, which is devoid of significant β-adrenergic blocking effect, before and after isoproterenol infusion.Methods and ResultsAction potential duration at 90% repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused withd-sotalol anddl-sotalol 10−4mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90ford-sotalol anddl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD90shortened to less than control in papillary muscles treated withd-sotalol but notdl-sotalol on addition of isoproterenol 10−6mol/L: −31.2±3.5 to −18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively,P<.003. Single guinea pig ventricular myocytes were studied by the whole-cell patch clamp method. Time-dependent (Iout) and total (Itot) outward current in response to a 300-ms pulse to 20 mV and tail current (Itail) to −35 mV were measured after Ca2+channel block and Na+channel inactivation. Iout, Itail, and Itotwere reduced in myocytes perfused withd-sotalol anddl-sotalol 10−4mol/L: Iout, −36.1±4.1%, −40.5±3.3%; Itail, −59.3±4.6%, −62.2±11.1%; Itot, −27.3±4.3%, −50.0±11.8%. Ioutand Itotincreased to a greater degree in myocytes treated withd-sotalol thandl-sotalol on addition of isoproterenol 10−6mol/L: Iout, 100.3±20.6%, 11.3±7.6%,P=.002; Itot, 86.8±39.2%, −41.1±20.9%,P=.01. Itailtended to increase more in myocytes treated withd-sotalol thandl-sotalol on addition of isoproterenol, but the difference was not significant (−9.1±13.5%, −28.0±9.0%).ConclusionsThe β-adrenergic blocking property ofdl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy ofdl-sotalol in diminishing ventricular arrhythmia recurrence.