从索他洛尔电生理作用评价其抗心律失常作用

从索他洛尔 (sotalol)电药理和电生理作用探索其抗心律失常机制。方法 :①采用经典的微电极方法和膜片钳技术观察sotalol对豚鼠心肌细胞动作电位时程 (APD)和膜离子流的作用 ;②运用心内膜单相动作电位 (MAP)技术观察sotalol对狗APD、有效不应期 (ERP)的影响 ;③监测药物浓度与QT间期关系。结果 :①索他洛尔对内向整流性钾流、钠内流、慢钙内流无影响 ,仅对延迟整流性钾流 (IK)有抑制作用 ;②索他洛尔可延长APD ,呈反转使用依赖 ;③静脉注射索他洛尔后 ,QTc ,APD90 和心室ERP均延长 ,缺血区心肌与非缺血区心肌对索他洛尔的反应一致 ;④QT间期随血药浓度升高而延长 ,血药浓度随剂量增大而上升。结论 :索他洛尔阻滞IK 外流、延长APD ,呈反转使用依赖。索他洛尔延长QTc与血药浓度呈正相关。因此 ,如能掌握索他洛尔特性 ,本药还不失为一安全有效的Ⅲ类抗心律失常药物。

From Electrophysiologic Effects of D,L-Sotalol to Evaluate Its Mechanisms of Antiarrhythmias

From Electrophysiologic Effects of D,L-Sotalol to Evaluate Its Mechanisms of Antiarrhythmias.From electropharmacologic and electrophysiologic effects of d,l-Sotalol to study its mechanisms.Methods:①The classical microeletrode technique and patch-clamp technique were used to observe the effects of sotalol on the action potential duration (APD) and membrane ionic currents of cardiac myocytes from guinea-pig.②Using endocardium monophatic action potential technique to study the effect of sotalol on the APD,effective refectory period (ERP) of the dogs.③The relationship among the plasma concentration and QT duration was observed.Results:①Sotalol prolonged APD.Prolongation of APD was converse use-dependent.②Sotalol had effects on IK only but no effects on IK1,INa,ICa.③After sotalol intravenous injection,all of the APD,ventricular ERP and QTc was prolonged.The reaction to sotalol from ischmia portion and no-ischmia portion myocardia was consistent.④The QT duration was prolonged with the increasing plasma concentraiton which was increased with the dosage.Conclusions:Sotalol inhibit IK outward current and prolong APD.Its effects is converse use-dependent.The plasma concentration is positive correlation with prolongation of QTc.If the characteristic of sotalol is mastered,it could be a more safe and effective class Ⅲ antiarrhythemia drug.