MECHANISMS OF NEUROGENIC PULMONARY EDEMA

神经源性肺水肿的机制

• 批准号: 3342092
• 负责人: MICHAEL B MARON
• 金额: $ 5.75万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3342092
• 关键词: adrenalectomy; blood cell count; catecholamines; disease /disorder model; dyes; electrostimulus; head /neck injury; mathematical model; microcirculation; neuropharmacology; pulmonary circulation; pulmonary edema; pulmonary hypertension; sympathetic nervous system; trauma; vascular endothelium permeability; vascular resistance; vasoconstriction

Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNA trauma that intensely activates the sympathetic nervous system. Although NPE has generally been considered to be a hemodynamic form of edema caused by the translocation of a volume overload of blood from the systemic to the pulmonary circuit, important questions remain regarding the role that vascular barotraums (which may, in turn, result in increased protein permeability) and pulmonary vasoconstriction may play in the development of NPE. The purpose of this study will be to test the possibility that these mechanisms may be involved in the development of this disorder. The studies that will be conducted in this invesigation are aimed at the long-term objective of understanding the pathogenesis of this disorder. In Part One of this study, it will be detemrined if vascular damage occurs at pulmonary vascular pressures known to develop in patients with NPE. This will be done by mechanically raising vascular pressure to various levels in a canine isolated perfused lung lobe preparation and determining if the permeability (as evaluated by the hematocrit-protein double-indicator technique) to both total proteins and selected individual proteins (albumin, IgG, and IgM) is increased under these conditions and if it remains so after pressure is returned to control levels. In Part Two of the study, it will be determined if pumonary edema may continue to develop (due to increased permeability) after normal vascular pressures are reattained in a canine model of NPE, by making serial measurements of lung extravascular thermal water (thermal-dye double indicator technique). In these experiments, NPE will be produced by the intracisternal injection of veratrine. In Part Three of the study, it will be determined if pulmonary vasoconstriction occurs in veratrine-induced NPE, if the increase in vascular tone is mediated by adrenal catecholamines, and if there are changes in the pulmonary vascular resistance distribution (as evaluated by the double-occlusion technique) that may favor the development of edema. This will be done by studying the responses of a canine in situ perfused lung lobe preparation when the adrenals are intact and after adrenalectomy.

神经源性肺水肿 (NPE) 是一种水肿形式，可能在以下情况发生： CNA 创伤强烈激活交感神经系统。 尽管 NPE 通常被认为是一种血流动力学形式 由于血液容量超负荷从体内转移而引起的水肿 对于肺循环系统来说，重要的问题仍然存在 血管气压伤的作用（这可能反过来导致增加 蛋白质通透性）和肺血管收缩可能在 NPE的发展。 本研究的目的是测试 这些机制可能参与发展 这种紊乱。 本次调查将进行的研究是 旨在了解这种疾病发病机制的长期目标 紊乱。 在本研究的第一部分中，将确定血管是否 损害发生在已知患者体内发生的肺血管压力下 与NPE。 这将通过机械地将血管压力升高至 犬离体灌注肺叶制剂中的不同水平和 确定渗透性（通过血细胞比容蛋白评估）是否 双指示剂技术）对总蛋白和选定的个体 在这些条件下，蛋白质（白蛋白、IgG 和 IgM）会增加，如果 当压力恢复到控制水平后，这种情况仍然存在。 在第二部分中 该研究将确定肺水肿是否可能继续发展 （由于渗透性增加）正常血管压力后 通过对肺进行连续测量，在 NPE 犬模型中重新获得了 血管外热水（热染料双指示剂技术）。 在 这些实验中，NPE将通过脑池内注射产生 藜芦碱。 在研究的第三部分中，将确定肺部是否 如果藜芦碱引起的 NPE 增加，则血管收缩发生 血管张力是由肾上腺儿茶酚胺介导的，如果有 肺血管阻力分布的变化（通过评估 双闭塞技术）可能有利于水肿的发展。 这将通过研究原位灌注犬的反应来完成 当肾上腺完整时和肾上腺切除术后进行肺叶准备。