CLINICAL MODELS OF THE ADULT RESPIRATORY DISTRESS SYNDROME

（改编自申请人的摘要）：UCSD/急性肺损伤SCOR的该项目侧重于使用基于定义急性肺损伤的具体机制的观察的靶向干预来预防或改善急性肺损伤。用于这些项目的人体模型由接受肺动脉血栓内膜切除术（PT-E）的患者组成。这些患者中高达60%在PT-E后发生高渗透性水肿/再灌注肺损伤。本项目的目的是通过从PT-E和其他有ARDS风险的患者中连续收集血液和BALF样本，并分析这些样本的ALI标志物[中性粒细胞和蛋白质流入，细胞因子]，继续确定PT-E患者中这种独特的、可预测的肺损伤模型（IL-8、TNF-α）、氧化α 1蛋白酶抑制剂、谷胱甘肽水平和可溶性粘附分子（E-P-、L-选择素、ICAM-1、VCAM-1）]。这三项干预性试验提出了模拟，（2）使用抗氧化药物，（3）吸入一氧化氮在预防再灌注肺损伤的再灌注。 除了评估这三种干预措施的疗效和安全性外，还将在急性肺损伤之前、急性期和缓解期间采集系列血液和支气管肺泡灌洗标本。这些标本的分析将提供见解的细胞成分和介质，参与了急性肺损伤的启动和持续。这些标本将与UCSD其他SCOR项目的合作者共享，如果需要，还将与其他急性肺损伤SCOR共享。(End摘要）

(Adapted from the Applicant's Abstract): This project of the UCSD/ACUTE Lung Injury SCOR focuses on the prevention or amelioration of acute lung injury using targeted interventions based on observations which define the specific mechanisms responsible for acute lung injury. The human model used for these projects consists of patients undergoing pulmonary thromboendarterectomy (PT-E). Up to 60 percent of these patients develop a high permeability edema/reperfusion lung injury following PT-E. The aims of this project are to continue to define this unique, predictable, model of lung injury in PT-E patients by collecting sequential blood and BALF samples from PT-E and other patients at risk for ARDS and analyzing these samples for markers of ALI [neutrophil and protein influx, cytokines (IL-8, TNF-alpha), oxidized alpha1-proteinase inhibitor, glutathione levels, and soluble adhesion molecules (E-P-, L-selectins, ICAM-1, VCAM-1)]. The three interventional trials proposed analog, (2) use of an anti-oxidant drug, and (3) inhaled nitric oxide in the prevention of reperfusion of reperfusion lung injury. In addition to assessing the efficacy and safety of these three interventions, serial blood and bronchoalveolar lavage specimens will be collected prior to, during the acute phase, and during resolution of acute lung injury. Analysis of these specimens will provide insights into the cellular components and mediators that are involved in the initiation and perpetuation of acute lung injury. These specimens will be shared with collaborators working on other SCOR projects at UCSD and, if desired, with other Acute Lung Injury SCORs. (End of Abstract)