生物谷報道：來自Alabama大學Birmingham分校（UAB）的科學家發(fā)現(xiàn)，在肝臟移植手術(shù)過程中吸入一氧化氮（NO）能降低手術(shù)失敗的風險。
這種無色氣體能防止移植后肝臟受到再灌注傷害,，這是一種由體內(nèi)存儲血液迅速流向植入器官而引起的副作用,。研究結(jié)果發(fā)表在最新的《臨床檢查雜志》（Journal of Clinical Investigation）上。作者之一,，UAB病理學系副教授Rakesh Patel表示,，這項小型研究的初步結(jié)果還需要大型臨床實驗驗證。
Patel說,，NO究竟如何在細胞和分子水平上促進器官功能還不得而知,。但這對病人術(shù)后恢復的好處顯而易見：住院時間縮短、術(shù)后凝血和肝臟酶活性提高等,。UAB麻醉學家在移植手術(shù)中通過一個麻醉面具使病人吸入NO,。
整個研究是雙盲且對照的，也就是說一部分病人吸入NO,，而另一部分沒有,，并且病人和醫(yī)生都不知道誰吸入了NO。
Patel說："我們對于吸入了NO的病人術(shù)后的表現(xiàn)感到非常驚喜,。"結(jié)果還顯示吸入的NO降低了移植肝臟細胞的死亡率,。在沒有醫(yī)療監(jiān)護情況下吸入過量NO對人體有毒性。研究中病人使用的劑量大約是80ppm,，這對人體沒有危害,。
目前UAB正計劃與西雅圖的Washington大學、美國退伍軍人醫(yī)療保護部門合作開展大規(guī)模臨床測試,。UAB外科教授Devon Eckhoff認為,，由于再灌注傷害可能發(fā)生在多種移植器官中，科學家希望吸入的NO能有效作用于心臟,、肺,、腎臟、胰臟等器官,。
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況就可望得到改善。Eckhoff說："適于移植的器官增加將減少等待器官的時間,，從而挽救更多生命。"
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.
原文出處：
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
作者簡介：
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.
