Kennedy T P, Rao N V, Hopkins C, Pennington L, Tolley E, Hoidal J R
Department of Medicine, University of Tennessee Center for Health Sciences, Memphis 38163.
J Clin Invest. 1989 Apr;83(4):1326-35. doi: 10.1172/JCI114019.
We have developed a model of reperfusion injury in Krebs buffer-perfused rabbit lungs, characterized by pulmonary vasoconstriction, microvascular injury, and marked lung edema formation. During reperfusion there was a threefold increase in lung superoxide anion (O2-) production, as measured by in vivo reduction of nitroblue tetrazolium, and a twofold increase in the release of O2- into lung perfusate, as measured by reduction of succinylated ferricytochrome c. Injury could be prevented by the xanthine oxidase inhibitor allopurinol, the O2- scavenger SOD, the hydrogen peroxide scavenger catalase, the iron chelator deferoxamine, or the thiols dimethylthiourea or N-acetylcysteine. The protective effect of SOD could be abolished by the anion channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid, indicating that SOD consumes O2- in the extracellular medium, thereby creating a concentration gradient favorable for rapid diffusion of O2- out of cells. Our results extend information about the mechanisms of reperfusion lung injury that have been assembled by studies in other organs, and offer potential strategies for improved organ preservation, for treatment of reperfusion injury after pulmonary thromboembolectomy, and for explanation and therapy of many complications of pulmonary embolism.
我们建立了一个在Krebs缓冲液灌注的兔肺中再灌注损伤的模型，其特征为肺血管收缩、微血管损伤和明显的肺水肿形成。在再灌注期间，通过体内硝基蓝四氮唑还原法测定，肺超氧阴离子（O2-）生成增加了三倍，通过琥珀酰化高铁细胞色素c还原法测定，释放到肺灌注液中的O2-增加了两倍。黄嘌呤氧化酶抑制剂别嘌呤醇、O2-清除剂超氧化物歧化酶（SOD）、过氧化氢清除剂过氧化氢酶、铁螯合剂去铁胺，或硫醇类的二甲基硫脲或N-乙酰半胱氨酸可预防损伤。阴离子通道阻滞剂4,4'-二异硫氰基-2,2'-芪二磺酸可消除SOD的保护作用，这表明SOD在细胞外介质中消耗O2-，从而形成有利于O2-从细胞中快速扩散的浓度梯度。我们的结果扩展了通过其他器官研究积累的关于再灌注肺损伤机制的信息，并为改善器官保存、治疗肺血栓栓塞切除术后的再灌注损伤以及解释和治疗肺栓塞的许多并发症提供了潜在策略。
