LUNG MICROVASCULAR INJURY DUE TO AIRWAY PRESSURE

气道压力导致的肺微血管损伤

• 批准号: 3352906
• 负责人: JAMES Courtney PARKER
• 金额: $ 9.04万
• 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/3352906
• 关键词: endotoxins; histopathology; 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，呼吸系统的呼吸机支持 失败本身可能会导致肺损伤。为了支持这一点 假设，我们最近报告了肺活量的增加 超过42 cmH2O的气道峰值压(Paw)的微血管通透性 在隔离的狗肺里。这些研究将确定那些病理性的和 降低微血管损伤阈值的生理机制 由Paw提供。我们将使用隔离的灌流肺制剂 将测定毛细管过滤系数(Kf，c)对蛋白质的反射 浮肿的系数、等压、临界毛细管压力 形成、毛细血管前后阻力比、总血管阻力、 微血管和大血管阻力、血管顺应性和肺 合规性。这些测量具有足够的灵敏度和可重复性 微血管通透性的相对较小差异和 可以可靠地检测到血管阻力的分布。我们会 微血管损伤阈值的确定及其作用机制的研究 正压和呼气压力(PEEP)：(1)开胸和闭胸 兔测定限量充气效果；(2)犬 肺内小支气管用微珠和生理盐水栓塞术产生 异质性肺充盈；(3)成人肺重复灌洗至 降低肺泡内表面张力；(4)肺表面活性物质缺乏过早 肺和新生犬肺；(5)已存在分级的成年犬肺 油酸、盐酸吸入或吸入引起的微血管损伤 内毒素。此外，白细胞和组织氧的渗透 爪部损伤后的根治性损害将在完好无损的狗和 毛细管泄漏部位的位置将使用甲基 甲基丙烯酸酯是微循环的铸型。这些研究应该会揭示 肺过度扩张、先前存在的毛细血管损伤、局部塌陷 局部剪应力导致爪部损伤，损伤部位 如果PEEP限制了高Paw对微血管的损伤，则发生。