LUNG MICROVASCULAR INJURY DUE TO AIRWAY PRESSURE

气道压力导致的肺微血管损伤

基本信息

批准号：
3352910
负责人：
JAMES Courtney PARKER
金额：
$ 7.62万
依托单位：
UNIVERSITY OF SOUTH ALABAMA
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-04-03 至 1990-06-30
项目状态：
已结题

项目摘要

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.

长期以来一直认为呼吸道的通气支持失败本身可能导致肺部损伤。支持这个假设，我们最近报道了肺部的增加高于42 CMH2O的高峰气道压力（PAW）的微血管通透性在孤立的狗肺中。研究将确定那些病理学和生理机制降低了微血管损伤的阈值由爪子。我们将使用孤立的灌注肺部制剂将测量毛细管过滤系数（KF，C）蛋白反射系数，等法压力，水肿的临界毛细管压力形成，毛细血管后的抗性比，总血管阻力，微血管和大血管耐药性，血管依从性和肺遵守。这些测量值足够敏感且可重复微血管通透性和相对适度的差异和可以可靠地检测到血管抗性的分布。我们将确定微血管损伤的阈值PAW和阳性和呼气压力（PEEP）在：（1）开放和闭合的胸部兔子确定通货膨胀量限制的影响；（2）狗肺有小支气管，含有微片和盐水可产生异质肺通胀；（3）成年肺反复灌输减少肺泡内表面张力；（4）表面活性剂不足过早肺和新生狗肺；（5）成人狗肺有先前的分级油酸，HC1抽吸或内毒素。另外，白细胞和组织氧的浸润爪受伤后的根本损伤将在完整的狗中确定毛细管泄漏部位的位置将使用甲基寻求微循环的甲基丙烯酸酯铸件。这些研究应该揭示肺过量，现有毛细管损伤，区域崩溃如何区域剪切应力有助于爪子损伤发生并且如果窥视限制了高爪的微血管损伤。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lung edema caused by high peak inspiratory pressures in dogs. Role of increased microvascular filtration pressure and permeability.

DOI：
10.1164/ajrccm/142.2.321
发表时间：
1990-08
期刊：
The American review of respiratory disease
影响因子：
0
作者：
James C. Parker;Lucrecia A. Hernandez;Gesina L. Longenecker;Keith J. Peevy;Walter H. Johnson
通讯作者：
James C. Parker;Lucrecia A. Hernandez;Gesina L. Longenecker;Keith J. Peevy;Walter H. Johnson

Mechanical ventilation increases microvascular permeability in oleic acid-injured lungs.

机械通气增加油酸损伤肺部的微血管通透性。