Kobayashi S, Tadokoro H, Rydén L, Sjöquist P O, Haendchen R V, Corday E
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles.
Cardiovasc Drugs Ther. 1993 Feb;7(1):159-67. doi: 10.1007/BF00878325.
Previous studies have demonstrated pronounced ischemic zone myocardial concentrations of metoprolol following coronary venous retroinfusion in pigs with coronary artery ligation. The effect of coronary venous retroinfusion of metroprolol on myocardial infarct size was studied in 16 pentobarbital-anesthetized open-chest pigs undergoing 60-minute occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. Pigs in the experimental group (n = 8) were given 0.4 mg/kg (1.0 mg/ml) of metroprolol via the anterior interventricular vein over a period of 5 minutes, beginning immediately after coronary occlusion followed by 0.2 mg/kg/hr intravenously. Control pigs (n = 8) received the same volume of saline as the treated group. The risk area and the necrotic area were assessed by monastral blue dye and triphenyl tetrazolium chloride staining, respectively. Metoprolol did not influence hemodynamics. Plasma concentrations of metoprolol were within therapeutic levels. The administration of the beta-blocker resulted in a trend toward reduced norepinephrine concentrations, both in the aorta and coronary vein after coronary occlusion, but it did not prevent norepinephrine overflow following reperfusion. Infarct size expressed as a percentage of the risk area was 77 +/- 11% in the control group and 75 +/- 12% (mean +/- SD; NS) in the treated group. Thus, metoprolol retroinfusion did not reduce infarct size and did not prevent catecholamine overflow after reperfusion. It is concluded that the beneficial effects of metroprolol in acute infarction are probably unrelated to local beta-adrenergic blockade, at least in the pig, an animal with a paucity of coronary collateral blood flow.
先前的研究表明，在冠状动脉结扎的猪中进行冠状静脉逆向灌注后，美托洛尔在缺血区心肌中的浓度显著升高。本研究在16只戊巴比妥麻醉的开胸猪中，观察了冠状静脉逆向灌注美托洛尔对心肌梗死面积的影响。这些猪先接受60分钟的左前降支冠状动脉闭塞，随后再灌注3小时。实验组（n = 8）的猪在冠状动脉闭塞后立即开始，通过前室间静脉在5分钟内给予0.4 mg/kg（1.0 mg/ml）美托洛尔，随后以0.2 mg/kg/小时的速度静脉给药。对照组（n = 8）给予与治疗组相同体积的生理盐水。分别通过单星蓝染料和氯化三苯基四氮唑染色评估危险区和坏死区。美托洛尔不影响血流动力学。美托洛尔的血浆浓度在治疗水平范围内。给予β受体阻滞剂后，冠状动脉闭塞后主动脉和冠状静脉中的去甲肾上腺素浓度有降低趋势，但并不能防止再灌注后去甲肾上腺素溢出。以危险区百分比表示的梗死面积在对照组中为77±11%，在治疗组中为75±12%（平均值±标准差；无显著性差异）。因此，逆向灌注美托洛尔并不能减少梗死面积，也不能防止再灌注后儿茶酚胺溢出。结论是，美托洛尔在急性梗死中的有益作用可能与局部β肾上腺素能阻滞无关，至少在猪这种冠状动脉侧支血流较少的动物中是这样。
