John D. Lang, M.D., Alvin B. Smith, M.D., Luc Frenette, M.D., Richard C. Cross, M.D., Rakesh P. Patel, M.D.
麻醉科，VA Puget Sound 医疗保健系统，华盛顿大学医学院，西雅图，华盛顿。

  肝脏移植中缺血再灌注（IR）损伤可能会导致器官失功能和功能衰竭，它所表现出来的部分特征是丧失一氧化氮（NO）生物利用度。吸入一氧化氮（iNO）是无毒的，无血流动力学影响，且全身血管IR损伤通过吸入一氧化氮，肺外影响的集中度相对较高（80ppm）。在此项前瞻性、盲法、安慰剂的对照组研究中，我们假设进行原位肝移植的患者吸入一氧化氮（80ppm）能够抑制肝性IR损伤、改善移植术后肝功能，随后对该假设进行了评估。在手术期间，患者随机接受安慰剂(n = 10)或iNO(n = 10)。根据冷缺血时间和患者的性别进行调整后发现，iNO能明显缩短住院时间；评估肝功能的血清转氨酶（ALT与AST）和凝血时间（PT与PTT）显示，iNO确实能加速移植后肝功能的恢复。在肝组织中灌注炎性标记物1小时之后，iNO丝毫没有影响该标记物的变化，但却显著降低了细胞凋亡，因此暗示着该疗法能限制IR诱发的细胞毒性。循环无代谢产物的评估表明，可能性最大的iNO肺外影响传感器是循环性亚硝酸盐（见图1）。



Inhaled Nitric Oxide Accelerates Restoration of Liver Function Following Adult Liver Transplantation
John D. Lang, M.D., Alvin B. Smith, M.D., Luc Frenette, M.D., Richard C. Cross, M.D., Rakesh P. Patel, M.D.
The Department of Anesthesiology, VA Puget Sound Health Care System, The University of Washington School of Medicine, Seattle, Washington
Ischemia-reperfusion (IR) injury in transplanted livers may contribute to organ dysfunction and failure, and is characterized in part by loss of nitric oxide (NO) bioavailability. Inhalation of NO (iNO) is nontoxic, devoid of hemodynamic effects and at relatively higher concentrations (80ppm) exerts extrapulmonary effects via inhibition of IR injury in systemic vascular beds. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of iNO (80ppm) to patients undergoing orthotopic liver transplantation would inhibit hepatic IR injury and result in improved liver function. Patients were randomized to receive either placebo (n = 10) or iNO (n = 10) with administration occurring only during the operative period. When adjusted for cold ischemia time and gender, iNO significantly reduced the hospital length of stay and evaluation of liver function by serum transaminases (ALT and AST) and coagulation (PT and PTT) times indicated iNO improved the rate at which liver function was restored post-transplantation. iNO did not affect changes in inflammatory markers in liver tissue 1hr post-reperfusion, but did significantly lower apoptosis, suggesting this therapy limits IR induced cytotoxicity. Evaluation of circulating NO-metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was circulating nitrite.[figure1]

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