Lamontagne D, Yamaguchi N, Nadeau R, De Champlain J, Godin D, Campeau N
Eur J Pharmacol. 1986 Apr 9;123(1):1-10. doi: 10.1016/0014-2999(86)90680-1.
The pharmacological actions of sotalol, (-)-propranolol and prazosin on norepinephrine (NE) concentration and creatine kinase (CK) activity in the coronary sinus blood of the ischemic heart were studied in open-chest dogs. A 60 min occlusion of the left anterior descending coronary artery was followed by a reperfusion period of 30 min. In saline-treated dogs, a significant increase in coronary sinus NE concentration occurring 30 s after the onset of reperfusion was followed by a rapid decrease to the initial value within 15 min. CK activity increased gradually and continuously starting 5 min after the beginning of reperfusion. A good correlation (r = 0.9, n = 8, P less than 0.05) was obtained in saline-treated dogs when the calculated slope of the time-activity curves for CK release was plotted against the corresponding peak concentration of NE. The increase in coronary sinus NE concentration upon reperfusion was accompanied by an increased arrhythmic ratio. Sotalol (5 mg/kg i.v.) diminished the increase in coronary sinus NE concentration along with a significant decrease in the arrhythmic ratio. The administration of either (-)-propranolol (0.1 mg/kg i.v.) or prazosin (1 mg/kg i.v.) did not significantly affect the increase in coronary sinus NE concentration. The arrhythmic ratio was significantly reduced by prazosin but not by (-)-propranolol. The rise in coronary sinus CK activity was significantly diminished in the presence of either sotalol, (-)-propranolol or prazosin. These results suggest that the occurrence of severe ventricular arrhythmias upon reperfusion may be related to the action of the increased myocardial NE on the cardiac alpha-adrenoceptors. The increased coronary sinus CK activity suggests that increased cardiac sympathetic activation may accelerate or aggravate the myocardial damage. We conclude that the antiarrythmic effect of sotalol may be due at least in part to its inhibitory action on the release of cardiac NE upon reperfusion.
在开胸犬身上研究了索他洛尔、（-）-普萘洛尔和哌唑嗪对缺血心脏冠状窦血中去甲肾上腺素（NE）浓度和肌酸激酶（CK）活性的药理作用。左冠状动脉前降支闭塞60分钟后，再灌注30分钟。在生理盐水处理的犬中，再灌注开始30秒后冠状窦NE浓度显著升高，随后在15分钟内迅速降至初始值。CK活性在再灌注开始5分钟后逐渐持续增加。在生理盐水处理的犬中，当绘制CK释放时间-活性曲线的计算斜率与NE的相应峰值浓度时，获得了良好的相关性（r = 0.9，n = 8，P < 0.05）。再灌注时冠状窦NE浓度的增加伴随着心律失常发生率的增加。索他洛尔（5mg/kg静脉注射）减少了冠状窦NE浓度的增加，同时心律失常发生率显著降低。给予（-）-普萘洛尔（0.1mg/kg静脉注射）或哌唑嗪（1mg/kg静脉注射）均未显著影响冠状窦NE浓度的增加。哌唑嗪显著降低了心律失常发生率，但（-）-普萘洛尔没有。在索他洛尔、（-）-普萘洛尔或哌唑嗪存在的情况下，冠状窦CK活性的升高显著降低。这些结果表明，再灌注时严重室性心律失常的发生可能与心肌NE增加对心脏α-肾上腺素能受体的作用有关。冠状窦CK活性增加表明心脏交感神经激活增加可能加速或加重心肌损伤。我们得出结论，索他洛尔的抗心律失常作用可能至少部分归因于其对再灌注时心脏NE释放
