Crockett T R, Sharif I, Kane K A, Wainwright C L
Department of Physiology & Pharmacology, University of Strathclyde, Glasgow Scotland, UK.
J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S297-9. doi: 10.1097/00005344-200036051-00087.
The aim of this study was to investigate whether the endothelin-B- (ETB) receptor agonist sarafotoxin 6c (S6c) can protect against ischaemia-induced cardiac arrhythmias. Arrhythmias were induced by a 30 min period of coronary artery occlusion in pentobarbitone-anaesthetized male rats, or in Langendorff-perfused rat hearts. Rats or rat hearts were administered a bolus dose of vehicle or S6c (0.8 nmol/kg i.v. or 10(-8) M into the coronary circulation, respectively) 5 min before the onset of ischaemia. In vivo administration of S6c significantly reduced the incidence of ventricular fibrillation (VF) from 59% to 13% and the number of premature ventricular beats. This effect was associated with a transient fall in mean arterial blood pressure. In isolated hearts, S6c reduced significantly both the incidences of ventricular tachycardia (VT) and VF while having no statistically significant effect on coronary perfusion pressure. This is the first report to show that stimulation of ETB-receptors, with a bolus dose of S6c, has an antiarrhythmic effect on rat hearts both in vivo and in vitro, suggestive of a direct effect on the myocardium.
本研究的目的是调查内皮素 - B（ETB）受体激动剂沙拉新（S6c）是否能预防缺血诱导的心律失常。在戊巴比妥麻醉的雄性大鼠或Langendorff灌注的大鼠心脏中，通过30分钟的冠状动脉闭塞诱导心律失常。在缺血发作前5分钟，给大鼠或大鼠心脏分别静脉推注一剂溶媒或S6c（分别为0.8 nmol/kg静脉注射或10⁻⁸ M注入冠状动脉循环）。体内给予S6c可显著降低室颤（VF）发生率，从59%降至13%，并减少室性早搏数量。这种作用与平均动脉血压的短暂下降有关。在离体心脏中，S6c显著降低室性心动过速（VT）和VF的发生率，而对冠状动脉灌注压无统计学显著影响。这是第一份表明静脉推注一剂S6c刺激ETB受体对大鼠心脏在体内和体外均有抗心律失常作用的报告，提示对心肌有直接作用。
