Gibson J K, Stewart J R, Li Y P, Lucchesi B R
J Cardiovasc Pharmacol. 1983 Jul-Aug;5(4):517-24. doi: 10.1097/00005344-198307000-00002.
The electrophysiologic and antiarrhythmic actions of bretylium tosylate were studied after acute coronary artery occlusion and reperfusion in pentobarbital-anesthetized dogs. Three groups of animals were studied: Group I (n = 8) served as saline controls, Group II (n = 7) received bretylium tosylate (10 mg/kg i.v.) 60 min prior to coronary artery occlusion, and Group III (n = 5) received bretylium tosylate (30 mg/kg i.v.) in three divided doses over the 24 h prior to coronary artery occlusion. In Groups II and III the effective refractory period of the nonischemic myocardium was not altered by bretylium before or during the occlusion period, nor was it influenced by bretylium during the subsequent reperfusion period. In Group I the effective refractory period of the ischemic myocardium decreased 24 +/- 3.0% after coronary occlusion and increased 12 +/- 3% above the preocclusion level on reperfusion. In Group II the effective refractory period of the ischemic myocardium decreased 28 +/- 3.2% after coronary occlusion but did not overshoot preischemic levels on reperfusion. In Group III the effective refractory period decreased 15 +/- 3.8% following coronary occlusion and did not overshoot preocclusion levels during reperfusion. The ventricular activation times of the normal and ischemic myocardium were not affected by bretylium tosylate during occlusion or reperfusion in Group II or III. Significant reperfusion arrhythmias were observed only in Groups I and II. These data suggest that bretylium tosylate exerts its antiarrhythmic actions in ischemic myocardium by reducing the dispersion of cardiac refractoriness produced by coronary artery occlusion and, consequently, abolishing the abrupt change in cardiac refractoriness that follows coronary artery reperfusion. These antiarrhythmic actions of bretylium are pronounced in the chronically treated group, suggesting an electrophysiologic basis of the delayed antiarrhythmic actions of bretylium.
在戊巴比妥麻醉的犬急性冠状动脉闭塞和再灌注后，研究了甲苯磺酸溴苄铵的电生理和抗心律失常作用。研究了三组动物：第一组（n = 8）作为生理盐水对照，第二组（n = 7）在冠状动脉闭塞前60分钟静脉注射甲苯磺酸溴苄铵（10 mg/kg），第三组（n = 5）在冠状动脉闭塞前24小时分三次静脉注射甲苯磺酸溴苄铵（30 mg/kg）。在第二组和第三组中，闭塞期之前或期间，甲苯磺酸溴苄铵均未改变非缺血心肌的有效不应期，随后的再灌注期也未受其影响。在第一组中，冠状动脉闭塞后缺血心肌的有效不应期降低了24±3.0%，再灌注时比闭塞前水平升高了12±3%。在第二组中，冠状动脉闭塞后缺血心肌的有效不应期降低了28±3.2%，但再灌注时未超过缺血前水平。在第三组中，冠状动脉闭塞后有效不应期降低了15±3.8%，再灌注期间未超过闭塞前水平。在第二组或第三组的闭塞或再灌注期间，甲苯磺酸溴苄铵未影响正常和缺血心肌的心室激活时间。仅在第一组和第二组中观察到明显的再灌注心律失常。这些数据表明，甲苯磺酸溴苄铵通过减少冠状动脉闭塞产生的心脏不应期离散，从而消除冠状动脉再灌注后心脏不应期的突然变化，在缺血心肌中发挥抗心律失常作用。甲苯磺酸溴苄铵的这些抗心律失常作用在长期治疗组中更为明显，提示了甲苯磺酸溴苄铵延迟抗心律失常作用的电生理基础。
