MECHANISMS OF NEUROGENIC PULMONARY EDEMA

神经源性肺水肿的机制

• 批准号: 3342090
• 负责人: MICHAEL B MARON
• 金额: $ 7.81万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342090
• 关键词: baroreceptors; biological fluid transport; dogs; dyes; indicator dilution test; neuropharmacology; protein metabolism; pulmonary circulation; pulmonary edema; pulmonary hypertension; sympathetic nervous system; trauma; vascular endothelium permeability; vascular resistance

Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNS trauma that intensely activates the sympathetic nervous system (SNS). The long term objectives of this program are to determine the basic mechanisms by which such excessive SNS activity affects lung blood flow and fluid balance and how these mechanisms act in concert to product NPE. An understanding of these mechanisms is important for the design of effective preventive and treatment measures. This project is composed of 5 studies. Study 1 is designed to determine if the transient increase in venous return that occurs after massive SNS activation contributes to the pulmonary hypertension of NPE. This will be accomplished by comparing the degrees of pulmonary hypertension that develops after norepinephrine administration in the anesthetized dog under conditions where the venous return is either kept constant or allowed to increase. Study 2 is designed to determine how the pulmonary vascular macromolecular sieving capability is altered after injury by the high vascular pressures that occur in NPE. This will be accomplished by evaluating the ability of an in situ lung lobe preparation to sieve endogenous plasma proteins of varying molecular size before and after injury. Study 3 is designed to determine the relative contribution of extraalveolar vessel injury to the total vascular injury. This will be accomplished by determining how the filtration coefficients of arterial and venous extraalveolar vessel segments of an isolated perfused lung lobe preparation are altered by barotrauma. Study 4 is designed to determine the degree and time course of perfusion heterogeneity development in the lung after massive SNS activation. This will be accomplished by analyzing how the pulmonary vaScular and extravascular transport functions (determined by indicator dilution) change after SNS produced by intracisternal veratrine administration in the anesthetized dog. Study 5 is designed to determine if the perfusion heterogeneity is a consequence of the mechanical increases in pulmonary vascular pressure or results from other SNS- induced effects. This will be accomplished by comparing the pulmonary vascular and extravascular transport functions obtained from animals in which pulmonary vascular pressures are increased mechanically with those in which pressures are increased by SNS activation.

神经源性肺水肿（NPE）是一种水肿， 中枢神经系统创伤后，强烈激活交感神经系统 （SNS）。 该计划的长期目标是确定 这种过度SNS活动影响肺血的基本机制 流动和液体平衡以及这些机制如何与产品协同作用 NPE。 了解这些机制对于设计 有效的预防和治疗措施。 该项目由 5项研究。 研究1的目的是确定是否瞬时增加， 大量SNS激活后发生的静脉回流有助于 NPE肺动脉高压。 这将通过比较 去甲肾上腺素注射后肺动脉高压的程度 在麻醉犬中，在静脉给药的条件下， 回报要么保持不变，要么允许增加。 研究2是 旨在确定肺血管大分子筛选 损伤后，高血管压力改变了能力， 发生在NPE。 这将通过评估一个人的能力来实现。 原位肺叶制备以筛选 不同的分子大小 研究3旨在 确定肺泡外血管损伤的相对贡献 全血管损伤 这将通过确定 肺泡外动、静脉血管滤过系数 分离的灌注肺叶制备物的片段被改变， 气压伤 研究4的目的是确定程度和时间进程 大面积SNS后肺内灌注异质性的发展 activation. 这将通过分析肺如何 血管和血管外转运功能（由指示剂确定 脑池内注射藜芦碱产生SNS后的稀释度变化 在麻醉的狗中施用。 研究5旨在确定 如果灌注不均匀性是机械性 肺血管压力增加或由其他SNS引起- 诱导效应。 这将通过比较肺 血管和血管外运输功能， 肺血管压力会随着 其中压力通过SNS激活而增加。