PULMONARY EDEMA, LUNG VASCULAR INJURY AND LUNG FUNCTION

本课题旨在研究急性呼吸衰竭的发病机制 肺血管损伤后。 我们假设急性呼吸道感染 发生血管损伤（ARDS;非心源性肺水肿）导致的衰竭 由于肺水肿，缺氧性肺血管收缩功能丧失， 气道功能异常 我们假设所有这些变化， 无论病因如何，都是由阿吉多尼酸的代谢产物介导的 (and可能是其它相关的脂肪酸）和粒细胞。 我们建议 通过1）详细研究花生四烯酸的作用来验证这些假设 (and相关脂肪酸）及其代谢产物对肺功能的影响，2） 粒细胞与肺相互作用的详细研究 循环，肺白细胞淤滞的病理生理学影响， 3）对这些效应的理论和实验研究， 经血管的运输将定义压力的贡献， 流量、交换血管表面积和血管对肺的通透性 液体平衡，4）研究肺异常的发病机制， 人类疾病动物模型-革兰氏阴性内毒素血症、肺氧合 毒性、神经源性肺水肿和急性心肌梗死，以及 5)人类肺异常发病机制的研究 心源性和非心源性肺水肿的临床疗效 大剂量甲基强的松龙在成人呼吸道疾病患者中的应用 痛苦综合症 大多数动物研究将长期进行， 准备用于收集肺淋巴液的仪器化未麻醉绵羊; 肺水和渗透性的多指示剂稀释测量 将用于人类和动物。 三尖杉酯碱的测量， 血栓烷、花生四烯酸脂氧合酶产物和体外趋化性 分析以及肺力学的身体体积描记测量， 对研究也很重要 医学研究者， 生物工程、药理学、外科学和儿科学将参加 节目 这些研究将有助于明确肺结核的发病机制 血管损伤后的失败，提高我们对物理的理解， 影响血管损伤后肺液的因素， 了解影响肺液体平衡的物理因素，提供 肺水肿患者治疗方案设计的合理依据 （心源性或ARDS），并严格评估 甲基强的松龙治疗成人急性呼吸窘迫综合征

This program proposes to stdy the pathogenesis of acute respiratory failure following pulmonary vascular injury. We hypothesize that acute respiratory failure due to vascular injury (ARDS; non-cardiac pulmonary edema) occurs because of lung edema, loss of hypoxic pulmonary vasoconstriction and abnormal airway function. We hyupothesize that all of those changes, regardless of the etiology, are mediated by metabolites of archidonic acid (and perhaps other related fatty acids) and granulocytes. We propose to test these hypotheses by 1) detailed stdies of effects of arachidonic acid (and related fatty acids) and their metabolites on lung function, 2) detailed studies of the interaction of granulocytes with the lung circulation, the pathophysiological effects of pulmonary leukostasis and themechanisms of those effects, 3) theoretical and experimental studies of transvascular transport which will define the contributions of pressures, flows, exchanging vessel surface area and vascular permeability to lung fluid balance, 4) studies of the pathogenesis of lung abnormalities in four animal models of human disease-gram negative endotoxemia, pulmonary oxygen toxicity, neurogenic pulmonary edema, and acute myocardial infarction, and 5) studies of the pathogenesis of lung abnormalities in humans with cardiogenic and noncardiogenic pulmonary edema and the therapeutic effects of high dose methylprednisolone in patients with the adult respiratory distress syndrome. Most of the animal studies will be done in chronically instrumented unanesthetized sheep prepared for collection of lung lymph; multiple indicator dilution measurements of lung water and permeability will be used in humans and animals. Measurements of prostaglandins, thromboxanes, arachidonate lipoxygenase products and in vitro chemotaxis assays as well as body plethysmographic measurements of lung mechanics, will also be important to the studies. Investigators in Medicine, Bioengineering, Pharmacology, Surgery and Pediatrics will participate in the program. The studies will help to define the pathogenesis of lung failure following vascular injury, enhance our understanding of physical factors affecting lung fluid following vascular injury, enhance our understanding of physical factors affecting lung fluid balance, provide a rational basis for designing therapies for patients with pulmonary edema (cardiogenic or ARDS) and critically evaluate the effects of methylprednisolone in humans with ARDS.