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Effect of Nitric Oxide and Cytokines for Reperfusion Lung Injury in Living-donor Lung Transplantation

一氧化氮和细胞因子对活体肺移植再灌注肺损伤的影响

基本信息

批准号：
14571437
负责人：
GOTO Keiji
金额：
$ 0.77万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571437/
关键词：
lung transplantation living-donor reperfusion injury nitric oxide cytokine

项目摘要

We have succeeded a living-donor lober lung transplantation (LDLLT) at Okayama University Hospital in 1998, which was the first lung transplantation (LT) in Japan. The acute phase mortality rate of LT is higher than that of heart transplantation. A major cause of the death is reperfusion lung injury (RLI) and the treatment has not been established. Although nitric oxide (NO) inhalation therapy is supposed to improve oxygenation and prevent RLI and post-transplant pulmonary hypertension (PH), the usage is controversial. Patients undergoing LDLLT tend to develop PH because of the small size of the implanted lungs. The management of LDLLT is less understood. In order to improve the survival rate of LDLLT, we have established the treatment of LDLLT with inhalation NO and managed the patients. The overall actuarial survivals of LDLLT recipients have been reported as 70%, 54%, and 45% at 1, 3, and 5 years, respectively from the International Society for Heart and Lung Transplant registry. Be … More tween October 1998 and April 2004, we performed LDLLT in 30 critically ill patients with various lung diseases. All 30 recipients were discharged and are currently alive, with a follow-up period of 1 to 66 months. In spite of the complicated managements of LDLLT, 100% survival during the observation period is noteworthy. LDLLT can be applied to both pediatric and adult patients with very limited life expectancies. It might provide better survival than conventional cadaveric LT. We also studied intra-operative serum levels of key cytokines and polymorphonuclear elastase (PMN-E) in patients undergoing LDLLT surgery with cardiopulmonary bypass (CPB) in order to understand the pathophysiologic role. The NO inhalation started before the reperfusion. LDLLT patients demonstrated significant elevations of serum interleukin-6 (IL-6) and PMN-E during and after CPB. IL-6 production increased significantly after CPB. Serum tumor necrosis factor- α did not change significantly. It is expected to find new treatments to prevent ischemia-reperfusion lung injury in LT. Less

我们于1998年在冈山大学医院成功地进行了活体肺移植，这是日本第一例肺移植。肝移植急性期病死率高于心脏移植。死亡的主要原因是再灌注肺损伤(RLI)，治疗方法尚未确定。尽管一氧化氮(NO)吸入疗法被认为可以改善氧合，预防RLI和移植后肺动脉高压(PH)，但其使用仍存在争议。由于植入的肺体积较小，接受LDLLT的患者容易发生肺高压。人们对LDLLT的管理知之甚少。为提高肺移植的存活率，我们建立了吸入NO治疗肺移植的方法，并对患者进行了管理。根据国际心肺移植协会的登记，LDLLT受者在1年、3年和5年的总体精算存活率分别为70%、54%和45%。Be…在1998年10月至2004年4月期间，我们对30名患有各种肺部疾病的危重患者进行了低密度肺移植。所有30名受助者均已出院，目前仍活着，随访期为1至66个月。尽管处理复杂，但在观察期内100%的存活率是值得注意的。LDLLT可应用于预期寿命非常有限的儿童和成人患者。它可能比传统的身体肝移植提供更好的存活率。我们还研究术中关键细胞因子和中性粒细胞弹性蛋白酶(PMN-E)水平在体外循环(CPB)下的LDLLT手术患者中的变化，以了解其病理生理作用。吸入NO始于再灌流前。LDLLT患者CPB期间和术后血清IL-6和PMN-E显著升高。体外循环后IL-6产生明显增加。血清肿瘤坏死因子-α无明显变化。有望找到预防大鼠肺缺血再灌注性肺损伤的新方法。较少