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 中枢神经损伤会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， 水肿是由于血液从血管中大量超负荷转移而引起的。 对于肺循环系统，关于 血管气压伤的作用（这可能反过来导致增加 蛋白渗透性）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的可能性 这种混乱。 本研究将进行的研究是 目的是了解这种疾病的发病机制， disorder. 在本研究的第一部分，将确定是否存在血管 损伤发生在肺血管压力下， 关于NPE 这将通过机械地将血管压力升高至 犬离体灌注肺叶制备物中的各种水平， 确定渗透性（如通过血细胞比容-蛋白质 双指示剂技术）对总蛋白和选定的个体 蛋白质（白蛋白，IgG和IgM）在这些条件下增加，如果 在压力恢复到控制水平后，其保持不变。 第二部分中 这项研究将确定肺水肿是否会继续发展 (due增加的渗透性）， 在NPE的犬模型中，通过对肺进行系列测量， 血管外热水（热染料双指示剂技术）。 在 在这些实验中，NPE将通过脑池内注射 藜芦碱 在研究的第三部分，将确定肺 血管收缩发生在藜芦碱诱导的NPE，如果增加 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（如通过 双闭塞技术），这可能有利于水肿的发展。 这将通过研究犬在原位灌注 肾上腺完整时和肾上腺切除术后的肺叶准备。