Direct Effects of Esmolol and Landiolol on Cardiac Function, Coronary Vasoactivity, and Ventricular Electrophysiology in Guinea-Pig Hearts
Direct Effects of Esmolol and Landiolol on Cardiac Function, Coronary Vasoactivity, and Ventricular Electrophysiology in Guinea-Pig Hearts
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DOI：
10.1254/jphs.11202fp
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发表时间：
2012-02-01
影响因子：
3.5
通讯作者：
Ono, Kyoichi
中科院分区：
文献类型：
--
作者：
Shibata, Shigehiro;Okamoto, Yosuke;Ono, Kyoichi
超短效、选择性β（1）-肾上腺素能拮抗剂兰地洛尔和艾司洛尔广泛用于围手术期;然而，关于其对心脏的急性直接作用知之甚少。目前的研究利用Langendorff灌注心脏系统来测量心脏功能和血流动力学对每种药物的反应变化。此外，对分离的心室肌细胞进行电生理分析。在浓度>10 μ M时，直接应用艾司洛尔可显著降低左心室收缩压和心率，同时剂量依赖性地增加冠状动脉灌注压。艾司洛尔还以浓度依赖性方式缩短动作电位时程（APD），即使延迟整流K+电流或ATP敏感性K+电流被阻断时，该作用仍保持不变。此外，艾司洛尔剂量依赖性地抑制内向整流K+电流（I-KI）和L型Ca 2+电流（I-CaL），并增加外向电流。相比之下，兰地洛尔对心脏的影响最小。在京都模型计算机模拟中，单独抑制I-KI或I-CaL均未能缩短APD;然而，非时间依赖性外向电流的额外增加导致APD缩短，与艾司洛尔诱导的缩短相等。总之，艾司洛尔直接抑制心脏性能的作用显著大于兰地洛尔，该作用至少部分由艾司洛尔诱导的APD缩短介导。
The ultra-short acting, selective beta(1)-adrenergic antagonists landiolol and esmolol are widely used perioperatively; however, little is known about their acute direct actions on the heart. The current study utilized the Langendorff perfused heart system to measure changes in cardiac function and hemodynamics in response to each drug. Furthermore, electrophysiological analysis was performed on isolated ventricular myocytes. Direct application of esmolol significantly decreased systolic left ventricular pressure and heart rate at concentrations >10 mu M, while it dose-dependently increased coronary perfusion pressure. Esmolol also shortened the action potential duration (APD) in a concentration-dependent manner, an action maintained even when the delayed rectifier K+ current or ATP sensitive K+ current was blocked. Moreover, esmolol inhibited both the inward rectifier K+ current (I-KI) and the L-type Ca2+ current (I-CaL) and increased the outward current dose-dependently. In contrast, landiolol had minimal cardiac effects. In the Kyoto Model computer simulation, inhibition of either I-KI, or I-CaL, alone failed to shorten the APD; however, an additional increase in the time-independent outward current caused shortening of the APD, equal to that induced by esmolol. In conclusion, esmolol directly inhibits cardiac performance significantly more so than landiolol, an effect revealed to be at least in part mediated by esmolol-induced APD shortening.