LUNG INJURY, PERFLUOROCARBONS, AND HEMORRHAGIC SHOCK

本研究将确定四种趋化细胞因子的作用 （MIPalpha、MCP-1、MIP-2和CINC）在急性肺损伤发展中的作用 (ALI)出血性休克后，并将探讨 全氟化碳部分液体通气对这些表达 炎症介质。急性肺损伤（ALI）是一种并发症， 发生在多达40%的创伤，术中 围产期和其他与急性重度失血相关的事件。的 出血诱导肺损伤的机制，特别是 对中性粒细胞向肺中的募集知之甚少。部分 液体通风（PLV，部分全氟化碳的气体通风， 填充肺）目前用于呼吸衰竭患者， 改善气体交换和肺力学。本实验室 产生了大量的动物数据，将全氟化碳PLV与 在急性肺损伤情况下的肺保护作用。模型中 失血性休克，我们已经表明，PLV减少中性粒细胞， 肺中的积聚和毛细血管渗漏。我们假设 在失血性休克的情况下发生急性肺损伤， 依赖于趋化因子的表达， 通气将导致这些肽的减少。 利用大鼠失血性休克诱导的肺损伤模型，我们打算 系统地确定中性粒细胞的存在和相关性- 在急性失血后吸引细胞因子。由于肺损伤， 出血可能是循环或局部介质活性结果， 分析血清和肺趋化因子的表达。ELISA和北方 印迹分析将用于定量细胞因子和趋化因子- 调控静脉内和腹膜内阻断抗体研究将 以评估每种蛋白质对中性粒细胞的贡献 积累和毛细渗漏。一旦相关趋化因子 确定，我们将研究部分液体通气对 这些蛋白质的表达。预期效果更好 趋化因子在失血性休克诱导的急性 肺损伤和更深入地了解抗炎作用 部分液体通气对于申请人，该计划将提供 在活跃的学术环境中进行一段时间的紧张研究训练 重点是科学方法和技术技能， 急性肺损伤的研究和评价新的 治疗呼吸衰竭。

This study will determine the role of four chemoattractant cytokines (MIPalpha, MCP-1, MIP-2, and CINC) in the development of acute lung injury (ALI) following hemorrhagic shock and will explore the impact of perfluorocarbon partial liquid ventilation on the expression of these inflammatory mediators. Acute lung injury (ALI) is a complication occurring in as many as 40 percent of traumatic, intraoperative peripartum, and other events associated with acute severe blood loss. The mechanism by which hemorrhage induces lung injury, specifically the recruitment of neutrophils into the lung, is poorly understood. Partial liquid ventilation (PLV, gas ventilation of partially perfluorocarbon- filled lungs) is currently used in patients with respiratory failure to improve gas exchanges and pulmonary mechanics. Our laboratory has generated a large body of animal data linking perfluorocarbon PLV with a lung-protective effect in the setting of acute lung injury. In a model of hemorrhagic shock, we have shown that PLV decreases neutrophil accumulation and capillary leak in the lung. We hypothesize that the development of acute lung injury in the setting of hemorrhagic shock is dependent on the expression of chemokines and that partial liquid ventilation will result in a reduction of these peptides. Using a rat model of hemorrhagic shock-induced lung injury, we intend to systematically determine the presence and relevance of neutrophil- attracting cytokines following acute blood loss. As lung injury following hemorrhage may be a result of circulating or local mediator activity, both serum and lung chemokine expression will be analyzed. ELISA and Northern Blot analysis will be used to quantify cytokine and chemokine up- regulation. Intravenous and intratracheal blocking antibody studies will be performed to assess each protein's contribution to neutrophil accumulation and capillary leak. Once the relevant chemokines are identified, we will examine the effect of partial liquid ventilation on the expression of these proteins. The expected results are better understanding of the role of chemokines in hemorrhagic shock-induced acute lung injury and greater insight into the anti-inflammatory effects of partial liquid ventilation. For the applicant, this program will provide a period of intense research training in an active academic environment with a focus on the scientific methodological and technical skills necessary for the study of acute lung injury and evaluation of new therapies for respiratory failure.