Brunvand H, Frłyland L, Hexeberg E, Rynning S E, Berge R K, Grong K
Department of Surgery, University of Bergen, Haukeland Hospital, Norway.
Eur J Pharmacol. 1996 Oct 24;314(1-2):99-107. doi: 10.1016/s0014-2999(96)00549-3.
This study examined the effect of carvedilol, a vasodilating beta-adrenoceptor antagonist and antioxidant, on lethal reperfusion injury in feline hearts subjected to 40 min of regional ischemia and 180 min of reperfusion. 30 open chest anaesthetized cats were randomized into three groups. A control (n = 10) was compared with a group given carvedilol before coronary artery occlusions (n = 10) and a group given carvedilol immediately before and during early reperfusion (n = 10). Regional myocardial function was measured by sonomicrometry. Infarct size was determined by staining the left ventricle with triphenyl tetrazolium chloride. Myocardial blood flow was measured by radiolabeled microspheres. Tissue levels of glutathione were measured after reperfusion. Infarct size was significantly reduced compared to control both when carvedilol was given before ischemia (0.2 +/- 0.1 vs. 17.6 +/- 3.6%, P < 0.05). and when given immediately before reperfusion (3.7 +/- 1.3 vs. 17.6 +/- 3.6%, P < 0.05). Regional shortening improved significantly and the incidence of ventricular fibrillation during early reperfusion was reduced in both groups treated with carvedilol compared to control. Oxidized glutathione did not differ between groups in the post-ischaemic myocardium. This study supports that lethal reperfusion injury is a significant phenomenon. Furthermore, carvedilol reduces infarct size and reperfusion arrhythmias, and improves post-ischaemic regional myocardial function by protecting against both ischaemic and lethal reperfusion injury. The present study does not answer whether it is the non-selective beta- or alpha 1-receptor antagonism, the antiarrhythmic or the antioxidant actions of carvedilol that is responsible for the protective effect.
本研究考察了卡维地洛（一种血管舒张性β-肾上腺素能受体拮抗剂及抗氧化剂）对猫心脏在经历40分钟局部缺血和180分钟再灌注后的致死性再灌注损伤的影响。30只开胸麻醉猫被随机分为三组。将一组对照组（n = 10）与一组在冠状动脉闭塞前给予卡维地洛的组（n = 10）以及一组在再灌注即刻及早期再灌注期间给予卡维地洛的组（n = 10）进行比较。通过超声测量仪测定局部心肌功能。用氯化三苯基四氮唑对左心室进行染色来确定梗死面积。通过放射性微球测量心肌血流量。再灌注后测量组织中的谷胱甘肽水平。与对照组相比，在缺血前给予卡维地洛时梗死面积显著减小（0.2±0.1对17.6±3.6%，P<0.05），在再灌注即刻给予时梗死面积也显著减小（3.7±1.3对17.6±3.6%，P<0.05）。与对照组相比，在接受卡维地洛治疗的两组中，局部缩短显著改善，且早期再灌注期间室颤发生率降低。缺血后心肌中氧化型谷胱甘肽在各组间无差异。本研究支持致死性再灌注损伤是一个重要现象。此外，卡维地洛可减小梗死面积和再灌注心律失常，并通过预防缺血性及致死性再灌注损伤来改善缺血后局部心肌功能。本研究未回答是卡维地洛的非选择性β或α1受体拮抗作用、抗心律失常作用还是抗氧化作用导致了这种保护效应。
