Evidence against the "early protection-delayed death" hypothesis of superoxide dismutase therapy in experimental myocardial infarction. Polyethylene glycol-superoxide dismutase plus catalase does not limit myocardial infarct size in dogs.
Evidence against the "early protection-delayed death" hypothesis of superoxide dismutase therapy in experimental myocardial infarction. Polyethylene glycol-superoxide dismutase plus catalase does not limit myocardial infarct size in dogs.
复制标题
反对超氧化物歧化酶治疗实验性心肌梗死的“早期保护延迟死亡”假说的证据。
DOI：
10.1161/01.res.67.3.636
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发表时间：
1990
影响因子：
20.1
通讯作者：
Reimer,KA
中科院分区：
文献类型：
--
作者：
Tanaka,M;Stoler,RC;FitzHarris,GP;Jennings,RB;Reimer,KA
我们之前发现，狗在缺血 40 或 90 分钟以及再灌注 4 天后，超氧化物歧化酶 (SOD) 并不能限制心肌梗塞的面积。由于其他一些研究表明，较短时间的再灌注后梗塞面积有限，因此我们推测，我们的阴性结果可能是由于 SOD 排泄后产生的超氧阴离子介导的晚期再灌注损伤所致。为了检验这种“早期保护延迟死亡”假说，我们检查了与聚乙二醇缀合的SOD（PEG-SOD）是否可以延长其循环半衰期，限制心肌梗塞的面积。回旋动脉闭塞90分钟，然后再灌注4天。再灌注前30分钟给予PEG-SOD（总剂量10,000单位/kg）和过氧化氢酶（55,000单位/kg）。治疗组的血浆 SOD 水平在再灌注开始时为 330 +/- 20 单位/ml，第 4 天为 140 +/- 10 单位/ml（循环半衰期，75 +/- 5 小时），而对照组为 5 +/- 1 单位/ml。治疗组 (n = 11) 的组织学梗死面积占危险区域的 37.1 +/- 4.2%，而对照组 (n = 10) 的组织学梗死面积为 44.5 +/- 6.2% (p = NS)。在对照组中，梗死面积和侧支血流量呈负相关。 PEG-SOD 和过氧化氢酶没有改变这种回归（通过协方差分析 p = NS）。因此，再灌注 4 天后测量时，梗塞面积不受限制，即使在整个再灌注期间血浆 SOD 超过 100 单位/ml。（摘要截断为 250 字）
We previously found that superoxide dismutase (SOD) did not limit myocardial infarct size after 40 or 90 minutes of ischemia and 4 days of reperfusion in dogs. Because some other studies have shown limitation of infarct size after shorter periods of reperfusion, we postulated that our negative results might be due to late reperfusion injury mediated by superoxide anions produced after excretion of SOD. To test this "early protection-delayed death" hypothesis, we have examined whether SOD, conjugated to polyethylene glycol (PEG-SOD) to prolong its circulating half-life, limited myocardial infarct size. The circumflex artery was occluded for 90 minutes followed by 4 days of reperfusion. PEG-SOD (total dose, 10,000 units/kg) and catalase (55,000 units/kg) were given during the 30 minutes before reperfusion. Plasma SOD levels in the treated group were 330 +/- 20 units/ml at the onset of reperfusion and 140 +/- 10 units/ml on day 4 (circulating half-life, 75 +/- 5 hours) versus 5 +/- 1 units/ml in controls. Histological infarct size was 37.1 +/- 4.2% of the area at risk in the treated group (n = 11) versus 44.5 +/- 6.2% in controls (n = 10) (p = NS). Infarct size and collateral blood flow were inversely related in controls; PEG-SOD and catalase did not shift this regression (p = NS by analysis of covariance). Thus, infarct size was not limited when measured after 4 days of reperfusion, even though plasma SOD exceeded 100 units/ml throughout this reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)