LUNG CAPILLARY PERMEABILITY WITH HIGH VASCULAR PRESSURE

高血管压下的肺毛细血管通透性

• 批准号: 3449483
• 负责人: MARY I TOWNSLEY
• 金额: $ 2.71万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3449483
• 关键词: blood osmolarity; capillary; complement pathway; disease /disorder model; lung alveolus; mathematical model; oleate; pulmonary circulation; pulmonary edema; pulmonary hypertension; radiotracer; vascular endothelium permeability

The proposed research is designed to address five specific problems: (1) to characterize the relationship in the lung between the capillary filtration coefficient and the osmotic reflection coefficient, which describe the capillary permeability to fluid and proteins respectively, over a wide range of pulmonary microvascular permeabilities and further, to correlate these changes with the accumulation of alveolar fluid and protein; (2) to determine the effect of high intravascular pressures on the pulmonary osmotic reflection coefficient - the threshold for and reversibility of pressure-induced injury will be assessed, as well as the dependence of the injury on the duration of the pressure stress; (3) to determine whether prior injury to the lung predisposes the pulmonary microvasculature to pressure-induced permeability changes; (4) to determine whether pressure-induced injury is associated with redistribution of blood flow in the lung; and (5) to evaluate the gross anatomic sites of pressure-induced versus chemically-induced lung injury - are there gross leaks or tears in the alveolo-capillary barrier? Pulmonary microvascular permeability will be assessed by measuring the capillary filtration coefficient and the osmotic reflection coefficient, the latter using osmotic transients, protein vs. hematocrit fluid filtration volumes and lymphatic flux analysis. The ability of both the pulmonary capillary and the alveolar epithelial-capillary endothelial barriers to sieve proteins will be determined. These parameters will be assessed in isolated, blood perfused canine lung lobes. The effects of high intravascular pressures will be tested in normal lung lobes and in those with modest lung injury induced by oleic acid or complement fragments. Regional distributions of pulmonary blood flow before and after injury will be determined by the distribution of radiolabelled microspheres. Finally, acrylic corrosion casts using a low viscosity acrylic material, will be made of the pulmonary vasculature to evaluate the gross anatomic locus of pressure- and permeability-induced injuries.

本研究拟解决五个具体问题：（1） 来描述肺内毛细血管 渗透系数和渗透反射系数， 分别描述了毛细血管对液体和蛋白质的渗透性， 在广泛的肺微血管通透性范围内， 将这些变化与肺泡液体的积聚相关联， 蛋白质;（2）确定高血管内压力对 肺渗透反射系数-阈值和 将评估压力诱导损伤的可逆性，以及 损伤对压力应力持续时间的依赖性;（3） 确定先前的肺损伤是否易患肺动脉高压， 微血管对压力诱导的渗透性变化的影响;（4）确定 压力引起的损伤是否与血液再分布有关 肺内血流;（5）评估肺动脉瘤的大体解剖部位 压力引起的肺损伤与化学引起的肺损伤-是否存在严重的 肺泡-毛细血管屏障的渗漏或撕裂？ 肺微血管 通过测量毛细管过滤来评估渗透性 系数和渗透反射系数，后者使用 渗透瞬变、蛋白质与红细胞压积液体过滤体积和 淋巴流量分析。 肺毛细血管和 肺泡上皮-毛细血管内皮屏障筛选蛋白 将被确定。 将在分离的血液中评估这些参数 灌注的犬肺叶。 高血管内压的影响 将在正常肺叶和中度肺损伤患者中进行测试 由油酸或补体片段诱导。 区域分布 受伤前后的肺血流量将由 放射性标记微球的分布。 最后，丙烯酸腐蚀 使用低粘度丙烯酸材料的铸件，将由肺动脉 血管系统，以评估压力的大体解剖学轨迹-以及 渗透性损伤。