Rao P S, Cohen M V, Mueller H S
J Mol Cell Cardiol. 1983 Oct;15(10):713-6. doi: 10.1016/0022-2828(83)90260-2.
Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
最近我们[1,2,3]已确定自由基和脂质过氧化物是急性心肌缺血期间的代谢中间产物。心肌缺血进展引发自由基产生的机制尚不清楚。基于体外研究，考虑以下可能性是可行的：(a)线粒体内电子支持系统解离，磷脂完整性改变，细胞色素氧化酶失活，导致半醌、黄素蛋白和超氧自由基释放；(b)细胞内/外代谢产物如NADH、乳酸黄素蛋白和儿茶酚胺积累并增加释放，它们自身相互反应或与O2和抗坏血酸反应；(c)次黄嘌呤代谢产物在黄嘌呤氧化酶存在下与O2相互作用；(d)钙内流激活磷脂酶，增强花生四烯酸代谢和超氧自由基产生。详细的体外放射生物学研究[4]表明，即使在非常低的O2张力下（PO2约6 mmHg时自由基反应速率为最大值的83%，PO2约1 mmHg时为50%）也会发生自由基反应，并且史密斯[5]已证明在仅含5% O2的气体混合物中孵育的大鼠脑匀浆中自由基过氧化反应相当迅速地发生。因此，缺血组织中的低氧张力足以支持自由基反应。如此产生的自由基可能通过攻击多不饱和膜脂质引发并增强脂质过氧化反应。
