REDUCTION IN EXPERIMENTAL INFARCT SIZE BY RECOMBINANT HUMAN SUPEROXIDE-DISMUTASE - INSIGHTS INTO THE PATHOPHYSIOLOGY OF REPERFUSION INJURY
REDUCTION IN EXPERIMENTAL INFARCT SIZE BY RECOMBINANT HUMAN SUPEROXIDE-DISMUTASE - INSIGHTS INTO THE PATHOPHYSIOLOGY OF REPERFUSION INJURY
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DOI：
10.1161/01.cir.74.6.1424
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发表时间：
1986-12-01
期刊：
影响因子：
37.8
通讯作者：
WEISFELDT, ML
中科院分区：
文献类型：
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作者：
AMBROSIO, G;BECKER, LC;WEISFELDT, ML
为了确定再灌注损伤的重要性以及自由基清除剂重组人超氧化物歧化酶 (h-SOD) 预防再灌注损伤的能力，开胸犬接受近端回旋冠状动脉闭塞 90 分钟，并且仅在再灌注时接受 h-SOD（400,000 IU 推注至左心房，然后在 1 小时内静脉输注 300,000 IU）或盐水。 48小时后，处死幸存的动物并测量危险区域（通过死后血管造影）和梗塞面积（通过大体病理学）。所有测量均由对治疗不知情的研究人员进行，并且密码仅在研究结束时才被破解。两组中缺血期间的血流动力学变量和侧支血流相似。对照动物 (n = 8) 的梗塞面积平均为 22.4 .+-。左心室的 3.1% 和 52.2 .+-。 7.1% 的风险区域，相比之下为 13.3 .+-。左心室的 0.8% 和 33.6 .+-。 h-SOD 治疗犬的危险区域为 2.1% (n = 8) (p < .05)。接受治疗的动物的梗塞不仅较小，而且表现出独特的“斑片性”，表明沿血管分布的保护。此外，对两组缺血期间测量的梗死面积和侧支血流之间关系的分析表明，在侧支血流最低的动物中，h-SOD 的保护作用最大。这项研究支持这样的观点，即缺血心肌的再灌注会导致细胞损伤的一个单独组成部分，这可能与回流时氧自由基的产生有关。由于 h-SOD 可预防的再灌注损伤在缺血最严重的心脏中最为明显，因此在再流时清除氧自由基可能为保护缺血心肌提供一种新颖且特别有前途的治疗方法。
To determine the importance of reperfusion injury and the ability of the free-radical scavenger recombinant human superoxide dismutase (h-SOD) to prevent it, open-chest dogs underwent 90 min of proximal circumflex coronary artery occlusion, and only at the moment of reperfusion received either h-SOD (400,000 IU bolus into the left atrium followed by a 300,000 IU iv infusion over 1 hr) or saline. After 48 hr the surviving animals were killed and measurements were made of the risk region (by postmortem angiography) and infarct size (by gross pathology). All measurements were made by investigators blinded to tretment given, and the code was broken only at the end of the study. Hemodynamic variables and collateral flow during ischemia were similar in the two goups. Infarct size in control animals (n = 8) averaged 22.4 .+-. 3.1% of the left ventricle and 52.2 .+-. 7.1% of the risk region, compared with 13.3 .+-. 0.8%of the left ventricle and 33.6 .+-. 2.1% of the risk region in h-SOD-treated dogs (n = 8) (p < .05). Infarcts in treated animals were not only smaller, but also exhibited a distinctive "patchiness", suggesting protection along vascular distributions. Furthermore, analysis of the relationship between infarct size and collateral flow measured during ischemia in the two groups indicated that protection by h-SOD was greatest in animals with the lowest collateral flows. This study supports the concept that reperfusion of ischemic myocardium results in a separate component of cell damage, presumably linked to the generaiton of oxygen free radicals on reflow. Since the h-SOD preventable reperfusion component of injury was most pronounced in hearts with the most severe ischemia, scavenging of oxygen radicals at the time of reflow may offer a novel and particularly promising therapeutic approach for the protection of ischemic myocardium.