Fukazawa Kyota, Lang John D
Kyota Fukazawa, Division of Transplant Anesthesiology, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, United States.
World J Hepatol. 2016 Dec 8;8(34):1489-1496. doi: 10.4254/wjh.v8.i34.1489.
Ischemia-reperfusion injury (IRI) continues to be a major contributor to graft dysfunction, thus supporting the need for therapeutic strategies focused on minimizing organ damage especially with growing numbers of extended criteria grafts being utilized which are more vulnerable to cold and warm ischemia. Nitric oxide (NO·) is highly reactive gaseous molecule found in air and regarded as a pollutant. Not surprising, it is extremely bioactive, and has been demonstrated to play major roles in vascular homeostasis, neurotransmission, and host defense inflammatory reactions. Under conditions of ischemia, NO· has consistently been demonstrated to enhance microcirculatory vasorelaxation and mitigate pro-inflammatory responses, making it an excellent strategy for patients undergoing organ transplantation. Clinical studies designed to test this hypothesis have yielded very promising results that includes reduced hepatocellular injury and enhanced graft recovery without any identifiable complications. By what means NO· facilitates extra-pulmonary actions is up for debate and speculation. The general premise is that they are NO· containing intermediates in the circulation, that ultimately mediate either direct or indirect effects. A plethora of data exists explaining how NO·-containing intermediate molecules form in the plasma as S-nitrosothiols (., S-nitrosoalbumin), whereas other compelling data suggest nitrite to be a protective mediator. In this article, we discuss the use of inhaled NO· as a way to protect the donor liver graft against IRI in patients undergoing liver transplantation.
缺血再灌注损伤（IRI）仍然是移植物功能障碍的主要原因，因此，随着越来越多的边缘供肝被使用（这些供肝更容易受到冷缺血和热缺血的影响），需要采取治疗策略来尽量减少器官损伤。一氧化氮（NO·）是一种在空气中发现的高活性气体分子，被视为一种污染物。不出所料，它具有极强的生物活性，并已被证明在血管稳态、神经传递和宿主防御炎症反应中发挥重要作用。在缺血条件下，NO·一直被证明能增强微循环血管舒张并减轻促炎反应，这使其成为器官移植患者的一种理想策略。旨在验证这一假设的临床研究取得了非常有前景的结果，包括肝细胞损伤减少和移植物恢复增强，且无任何可识别的并发症。NO·促进肺外作用的方式尚在争论和推测之中。一般的前提是，它们是循环中含NO·的中间体，最终介导直接或间接作用。有大量数据解释了含NO·的中间分子如何在血浆中以S-亚硝基硫醇（如S-亚硝基白蛋白）的形式形成，而其他令人信服的数据表明亚硝酸盐是一种保护性介质。在本文中，我们讨论了吸入NO·作为一种保护肝移植患者供肝免受IRI损伤的方法。
