CLINICAL MODELS OF THE ADULT RESPIRATORY DISTRESS SYNDROME

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(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)