LUNG MICROVASCULAR INJURY DUE TO AIRWAY PRESSURE

气道压力导致的肺微血管损伤

• 批准号: 3352909
• 负责人: JAMES Courtney PARKER
• 金额: $ 6.89万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-03 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352909
• 关键词: dogs; endotoxins; histopathology; laboratory rabbit; lipid peroxides; mathematical model; mature animal; microcirculation; newborn animals; premature infant human; pulmonary circulation; pulmonary edema; pulmonary surfactants; respiratory airway pressure; respiratory airway volume; respiratory insufficiency /failure; superoxides; vascular endothelium permeability; vascular resistance

It has long been hypothesized that ventilatory support for respiratory failure may in itself contribute to lung damage. In support of this hypothesis, we have recently reported an increase in pulmonary microvascular permeability for peak airway pressures (Paw) above 42 cmH2O in isolated dog lungs. The studies will determine those pathologic and physiologic mechanisms which lower the threshold for microvascular injury by Paw. An isolated perfused lung preparation will be used in which we will measure the capillary filtration coefficient (Kf,c) protein reflection coefficient, isogravimetric pressure, critical capillary pressure for edema formation, pre/post-capillary resistance ratios, total vascular resistance, microvascular and large vessel resistance, vascular compliance and lung compliance. These measurements are sufficiently sensitive and reproducible that relatively modest differences in microvascular permeability and the distribution of vascular resistance can be reliably detected. We will determine the threshold Paw for microvascular injury and the effect of positive and expiratory pressure (PEEP) in: (1) open and closed chested rabbits to determine the effect of limitation of inflation volume; (2) dog lungs with small bronchi embolized with microbeads and saline to produce heterogeneous lung inflation; (3) adult lungs repeatedly lavaged to decrease intra-alveolar surface tension; (4) surfactant deficient premature lungs and newborn dog lungs; (5) adult dog lungs with a pre-existing graded microvascular injury induced by either oleic acid, HC1 aspiration, or endotoxin. In addition, the infiltration of leukocytes and tissue oxygen radical damage after Paw injury will be determined in intact dogs and the location of the capillary leak sites will be sought using methyl methacrylate casts of the microcirculation. These studies should reveal how lung overdistention, pre-existing capillary damage, regional collapse and regional shear stresses contribute to Paw injury, where the damage occurs and if PEEP limits microvascular damage by high Paw.

长期以来，人们一直假设呼吸道疾病的辅助治疗 失败本身可能导致肺损伤。 为支持这一 假设，我们最近报道了肺动脉高压的增加， 气道峰压（Paw）高于42 cmH 2 O时的微血管通透性 在离体的狗肺里 这些研究将确定那些病理和 降低微血管损伤阈值的生理机制 的爪子。 将使用离体灌注肺制备， 将测量毛细管过滤系数（Kf，c）蛋白质反射 系数，等重压力，水肿临界毛细血管压力 形成，前/后毛细血管阻力比，总血管阻力， 微血管和大血管阻力、血管顺应性和肺 合规 这些测量具有足够的灵敏度和重现性 微血管渗透性的相对适度的差异， 可以可靠地检测血管阻力的分布。 我们将 确定微血管损伤的阈值Paw和 呼气正压（PEEP）：（1）开胸和闭胸 家兔测定限制充气量的效果;（2）犬 用微珠和盐水栓塞小支气管的肺， 不均匀肺膨胀;（3）成人肺反复灌洗， 肺泡内表面张力降低;（4）表面活性物质缺乏， 肺和新生犬肺;（5）具有预先存在的分级 微血管损伤诱导的油酸，盐酸吸入，或 内毒素 此外，白细胞和组织氧的浸润 将在完整犬中确定爪损伤后的根本性损伤， 毛细管泄漏点的位置将使用甲基 微循环的甲基丙烯酸酯模型。 这些研究应该揭示 肺过度膨胀，预先存在的毛细血管损伤，局部塌陷 和局部剪切应力有助于爪损伤， 如果PEEP限制了高Paw引起的微血管损伤。