MECHANISMS OF NEUROGENIC PULMONARY EDEMA

神经源性肺水肿的机制

• 批准号: 3342095
• 负责人: MICHAEL B MARON
• 金额: $ 7.94万
• 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/3342095
• 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）是一种可能发展的水肿形式 在CNS创伤强烈激活交感神经系统之后 （SNS）。 该程序的长期目标是确定 这种过度SNS活性影响肺血的基本机制 流量和流体平衡以及这些机制如何与产品共同起作用 NPE。 对这些机制的理解对于设计很重要 有效的预防和治疗措施。 这个项目由 5个研究。 研究1旨在确定瞬时增加 大规模SNS激活后发生的静脉回报有助于 NPE的肺动脉高压。 这将通过比较 去甲肾上腺素后发展的肺动脉高压程度 在静脉 退货要么保持恒定或允许增加。 研究2是 设计用于确定肺血管大分子筛分 高血管压力受伤后的能力会改变 发生在NPE中。 这将通过评估一个 原位肺叶制备以筛入筛子的内源血浆蛋白 受伤前后分子大小的变化。 研究3旨在 确定外肺化学血管损伤对 总血管损伤。 这将通过确定如何实现 动脉和静脉肺泡血管的过滤系数 孤立的灌注肺叶制剂的细分市场被改变 Barotrauma。 研究4旨在确定程度和时间课程 大量SNS后肺部灌注异质性发展 激活。 这将通过分析肺部如何实现 血管和血管外传输功能（由指标确定 稀释）SNS在肠内生效后的变化后变化 麻醉狗的管理。 研究5旨在确定 如果灌注异质性是机械的结果 肺血管压力升高或其他SNS的结果 诱导的效果。 这将通过比较肺部来完成 从动物中获得的血管和血管外转运功能 用这些肺血管压力增加了哪些肺血管压力 SNS激活增加了压力。