Weinbroum A A, Kluger Y, Ben Abraham R, Shapira I, Karchevski E, Rudick V
Department of Anesthesiology, Tel Aviv Sourasky Medical Center, Israel.
Transplantation. 2001 Jan 27;71(2):300-6. doi: 10.1097/00007890-200101270-00023.
Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels.
Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs.
Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility.
循环中的黄嘌呤氧化酶活性及所产生的氧化剂与器官移植或手术后其他器官因无复流-再灌注情况导致的肺再灌注损伤有关。N-乙酰-1-半胱氨酸（NAC）作为一种氧化剂清除剂，可促进在缺血过程中耗竭的还原型谷胱甘肽（GSH）的生成。我们最近证明，如果在缺血后肝脏再灌注期间给予NAC，其在保护肺免受再灌注损伤方面具有疗效。我们现在研究用NAC对肺进行预处理是否能减轻无复流-再灌注（缺血-再灌注，IR）后肺的呼吸或血管紊乱，以及这是否取决于肺GSH水平。
将大鼠离体肝脏稳定后，用改良的克雷布斯-亨泽莱特溶液（KH）灌注（对照组，n = 12）或使其缺血（无血流，IR-0，n = 12）2小时。与此同时，分离肺脏，进行通气并使其稳定（KH + 5%牛血清白蛋白）。对肝-肺对进行系列灌注（15分钟），然后仅对肺进行用累积溶液的再循环（45分钟）。另外三个对照组和三个缺血组包括在稳定期用100 mg·kg⁻¹、150或225 mg·kg⁻¹的NAC处理的肺（分别在2.5、3.7或5.5 mmol溶液中）。结果：以循环中的肝细胞成分表示的缺血性肝损伤与IR-0（未处理）以及IR-100和IR-225预处理的肺中肺动脉和通气压力升高至基线的70 - 100%、异常的湿重与干重比以及异常的支气管肺泡灌洗体积和内容物有关。NAC-150预处理对大多数参数起到了保护作用。IR-150肺组织中的GSH含量仅比IR-225高11%，但却是IR-0和IR-100 GSH肺中GSH含量的2倍。
用NAC对肺进行预处理可预防再灌注损伤，但并非呈剂量相关方式。尽管GSH组织含量增加解释了肺的保护作用，但NAC的非GSH依赖性活性也是一种可能性。
