MECHANISMS OF NEUROGENIC PULMONARY EDEMA

神经源性肺水肿的机制

• 批准号: 3342089
• 负责人: MICHAEL B MARON
• 金额: $ 5.53万
• 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/3342089
• 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; 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，可能在 强烈激活交感神经系统的CNA创伤。 尽管NPE通常被认为是一种血液动力学形式 由于从 系统到肺电路，关于 血管贝洛特人的作用（反过来可能导致增加 蛋白质渗透性）和肺血管收缩可能会在 NPE的开发。 这项研究的目的是测试 这些机制可能参与发展的可能性 这个疾病。 在此激发中将进行的研究是 旨在理解这一发病机理的长期目标 紊乱。 在这项研究的第一部分中，如果血管造 损伤发生在患者已知发生的肺血管压力下 与NPE。 这将通过机械地升高血管压力来完成 犬孤立的灌注肺叶制剂中的各种水平 确定渗透性是否（如血细胞比容蛋白评估 双向技术）至总蛋白质和选定的个体 在这些条件下，蛋白质（白蛋白，IgG和IgM）增加了 在压力返回控制水平后，它仍然如此。 在第二部分 该研究将确定是否可能继续发展pumonary水肿 （由于渗透率的提高）正常血管压力是 通过对肺的串行测量进行重新装置在NPE的犬模型中 血管外热水（热染色双重指示技术）。 在 这些实验，NPE将通过肠内注射产生 veratrine。 在研究的第三部分中，将确定是否肺 血管收缩发生在Veratrine诱导的NPE中，如果增加 血管张力是由肾上腺儿茶酚胺介导的，如果有 肺血管抗性分布的变化（通过 可能有利于水肿发展的双重钉技术。 这将通过研究原位灌注的犬的反应来完成 当肾上腺完好无损并在肾上腺切除术后进行肺叶制备。