Pasnani J S, Ferrier G R
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Pharmacol Exp Ther. 1994 Oct;271(1):184-92.
Pro- and antiarrhythmic effects of dl-sotalol and d-sotalol were compared with their electrophysiological actions in an isolated tissue model of simulated ischemia and reperfusion. Microelectrode recordings were made from endo- and epicardium of isolated guinea pig right ventricular free walls. An electrocardiogram also was recorded by two electrodes at opposite ends of the tissue bath. Regular stimulation was delivered to the endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Arrhythmias with characteristics of transmural reentry occurred in 33% of hearts in ischemia and 73% of hearts in early reperfusion. Arrhythmias were accompanied by prolongation of transmural conduction time (CT) and abbreviation of endocardial action potential duration (APD) and effective refractory period. Both dl-sotalol and d-sotalol (100 microM) significantly (P < .05) prolonged endocardial APD, effective refractory period and epicardial APD under preischemic conditions; however, these effects were lost during simulated ischemia and early reperfusion. dl-Sotalol abolished arrhythmias in ischemia and reduced the incidence of reperfusion arrhythmias to 30%. This agent attenuated prolongation of transmural CT by ischemia and decreased the incidence of conduction block. In contrast, d-sotalol (100 microM) increased arrhythmias in ischemia to 80% and did not change the incidence of reperfusion arrhythmias (60%). The proarrhythmic effects of d-sotalol were accompanied by prolongation of transmural CT, increased incidence of conduction block and decreased epicardial excitability. Thus, in this model of global ischemia and reperfusion, antiarrhythmic effects were observed with dl-sotalol but not with the predominantly type III isomer, d-sotalol.
在模拟缺血和再灌注的离体组织模型中，比较了消旋索他洛尔和右旋索他洛尔的促心律失常和抗心律失常作用及其电生理作用。从离体豚鼠右心室游离壁的心内膜和心外膜进行微电极记录。还通过组织浴两端的两个电极记录心电图。对心内膜进行规则刺激。将组织暴露于模拟缺血15分钟，然后用正常台氏液再灌注。具有透壁折返特征的心律失常在缺血时出现在33%的心脏中，在早期再灌注时出现在73%的心脏中。心律失常伴有透壁传导时间（CT）延长、心内膜动作电位时程（APD）缩短和有效不应期缩短。在缺血前条件下，消旋索他洛尔和右旋索他洛尔（100微摩尔）均显著（P<0.05）延长心内膜APD、有效不应期和心外膜APD；然而，在模拟缺血和早期再灌注期间，这些作用消失。消旋索他洛尔消除了缺血时的心律失常，并将再灌注心律失常的发生率降低至30%。该药物减轻了缺血引起的透壁CT延长，并降低了传导阻滞的发生率。相比之下，右旋索他洛尔（100微摩尔）使缺血时的心律失常增加至80%，且未改变再灌注心律失常的发生率（60%）。右旋索他洛尔的促心律失常作用伴有透壁CT延长、传导阻滞发生率增加和心外膜兴奋性降低。因此，在这种全心缺血和再灌注模型中，观察到消旋索他洛尔具有抗心律失常作用，而主要为Ⅲ类异构体的右旋索他洛尔则没有。
