《临床检查杂志》：吸入NO可提高肝移植手术成功率

生物谷

生物谷报道：来自Alabama大学Birmingham分校（UAB）的科学家发现，在肝脏移植手术过程中吸入一氧化氮（NO）能降低手术失败的风险。
    这种无色气体能防止移植后肝脏受到再灌注伤害，这是一种由体内存储血液迅速流向植入器官而引起的副作用。研究结果发表在最新的《临床检查杂志》（Journal of Clinical Investigation）上。作者之一，UAB病理学系副教授Rakesh Patel表示，这项小型研究的初步结果还需要大型临床实验验证。
      Patel说，NO究竟如何在细胞和分子水平上促进器官功能还不得而知。但这对病人术后恢复的好处显而易见：住院时间缩短、术后凝血和肝脏酶活性提高等。UAB麻醉学家在移植手术中通过一个麻醉面具使病人吸入NO。
       整个研究是双盲且对照的，也就是说一部分病人吸入NO，而另一部分没有，并且病人和医生都不知道谁吸入了NO。
    Patel说："我们对于吸入了NO的病人术后的表现感到非常惊喜。"结果还显示吸入的NO降低了移植肝脏细胞的死亡率。在没有医疗监护情况下吸入过量NO对人体有毒性。研究中病人使用的剂量大约是80ppm，这对人体没有危害。
    目前UAB正计划与西雅图的Washington大学、美国退伍军人医疗保护部门合作开展大规模临床测试。UAB外科教授Devon Eckhoff认为，由于再灌注伤害可能发生在多种移植器官中，科学家希望吸入的NO能有效作用于心脏、肺、肾脏、胰脏等器官。
    一旦更多器官能在移植后保持健康，那么目前器官短缺的情况就可望得到改善。Eckhoff说："适于移植的器官增加将减少等待器官的时间，从而挽救更多生命。"

Figure 1
iNO therapy and human liver transplantation. (A) Experimental protocol for administering placebo or iNO to patients and sample (blood and liver biopsy) collection. (B) Methemoglobin (metHb) levels as a function of blood draw. ^#P 0.001 for corresponding placebo versus iNO measurements by unpaired t test. (C) Volume of platelets transfused during surgery ^#P 0.05. (D and E) Average percent decrease in PT and PTT after surgery. Data are normalized to coagulation times measured immediately (<1 hour) after surgery and were 26.7 ± 1.4 seconds (placebo) and 34.4 ± 2.5 seconds (iNO) for PT and 54.6 ± 7.3 seconds (placebo) and 70.2 ± 6.5 seconds (iNO) for PTT. (F and G) Average percent decrease in serum ALT and AST levels after surgery. Data were normalized to ALT and AST levels measured immediately (<1 hour) after surgery and were 601.8 ± 145.4 U/l (placebo) and 689.3 ± 149.5 U/l (iNO) for ALT and 922.1 ± 228.7 U/l (placebo) and 940.9 ± 211.3 U/l (iNO) for AST. For data in panels D–G, *P 0.05, **P 0.01, ***P 0.001 for corresponding placebo versus iNO measurements. (H) Cox analysis of patient hospital length of stay. P = 0.034 adjusted for sex and cold ischemic time. Filled squares: placebo; filled circles: iNO.

原文出处：

September 4 2007, Volume 117, Issue 9

John D. Lang, Jr., Xinjun Teng, Phillip Chumley, Jack H. Crawford, T. Scott Isbell, Balu K. Chacko, Yuliang Liu, Nirag Jhala, D. Ralph Crowe, Alvin B. Smith, Richard C. Cross, Luc Frenette, Eric E. Kelley, Diana W. Wilhite, Cheryl R. Hall, Grier P. Page, Michael B. Fallon, J. Steven Bynon, Devin E. Eckhoff, and Rakesh P. Patel

Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation
J. Clin. Invest. 2007 117: 2583-2591. First Published on August 24, 2007; 10.1172/JCI31892 [Abstract] [Full Text] [PDF] Supplemental data

作者简介：

Rakesh P. Patel, PhD
Department of Pathology
University of Alabama, School of Medicine
Birmingham, Alabama

Organizing Committee

Presentation Title
Elucidating the Relative Roles of Nitrite, ATP and SNO-Hb in mediating Red-cell Dependent Hypoxic Vasodilation using the b93cys Knockout Mouse

Dr Patel received his PhD from the University of Essex, United Kingdom, in 1996. He joined the UAB Department of Pathology as a postdoctoral Fellow and is now an Associate Professor. Dr Patel is involved in research projects centered on defining the molecular mechanisms by which reactive oxygen and nitrogen species modulate acute and chronic inflammation. These involve understanding i) what factors regulate endothelial cell function during inflammation and ii) the reactions that occur between red blood cells, nitric oxide and nitrite during hypoxia and specifically how these regulate nitric oxide function in the vascular compartment iii) assessing the clinical efficacy of nitrite and inhaled nitric oxide in preventing ischemia-reperfusion injury.

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