PERINATAL PULMONARY MICROCIRCULATION AND LUNG FLUID

这项建议的总体目的是增进理解 对肺微循环和肺液平衡的影响 在出生之后。该项目包括要检查的研究 肺微血管压的发育差异 和蛋白质的通透性、途径和机制 出生前和出生后肺腔液体清除率，以及 肺微血管损伤的发病机制及预防 与早产有关。肺血流动力学，肺 液体过滤和微血管蛋白通透性 通过各种实验对胎儿和新生羔羊进行评估 方法，包括测量肺淋巴流量和淋巴 肺泡蛋白质清除率的直接显微穿刺法 液体和肺微血管压，指示剂稀释度 肺腔积液容量变化的量化研究 时间，重量法测定肺水含量，并在 肺上皮细胞离子转运的体外研究。具体目标 主要有：(1)比较大鼠肺微血管蛋白通透性 未麻醉的早产和足月胎羔羊 快速静脉注射对肺血管和淋巴流动的影响 生理盐水输注和左房压力升高；(2)通过 直接微穿刺液压力在潜在的空气空间和 肺表面的小动脉和小静脉， 在有和没有充气的情况下，在活的胎羊中； 确定胸膜腔作为一种途径 胎儿和新生羔羊的肺泡液体清除率；(4)观察 低蛋白血症使新生羔羊肺液排出缓慢；(5) 比较肺上皮细胞阳离子转运的差异 来自早产羔羊，有和没有先前的呼吸 窘迫；(6)观察粒细胞是否参与异常肺的形成 与呼吸窘迫相关的血管蛋白通透性 在早产羔羊身上；以及(7)测试表面活性物质的疗效 替代疗法在预防或减轻肺内皮细胞损伤中的作用 早产后发生在羊羔身上的损伤。肺 浮肿是许多类型新生儿肺的重要组成部分。 疾病。拟议的工作应该有助于澄清这些 条件的发展，以及通过什么手段可以最大限度地管理它们 有效地。

The overall purpose of this proposal is to improve understanding of the pulmonary microcirculation and lung fluid balance before and after birth. The project includes studies to examine developmental differences in pulmonary microvascular pressures and protein permeability, pathways and mechanisms invovled in prenatal and postnatal lung luminal liquid clearance, and the pathogenesis and prevention of lung microvascular injury associated with premature birth. Pulmonary hemodynamics, lung fluid filtration and microvascular protein permeability will be assessed in fetal and newborn lambs by various experimental methods, including measurement of lung lymph flow and lymph protein clearance, direct micropuncture measurement of alveolar liquid and pulmonary microvascular pressures, indicator dilution studies to quantify changes in lung luminal liquid volume over time, gravimetric determination of lung water content, and in vitro studies of lung epithelial cell ion transport. Specific aims are: (1) to compare lung microvascular protein permeability of unanesthetized premature and term fetal lambs by assessing their pulmonary vascular and lymph flow responses to rapid intravenous saline infusion and left atrial pressure elevation; (2) to measure by direct micropuncture liquid pressures in potential air spaces and small pulmonary arterioles and venules at the surface of the lung, with and without air inflation, in living fetal lambs; (3) to determine the importance of the pleural space as a pathway for alveolar liquid clearance in fetal and newborn lambs; (4) to see if hypoproteinemia slows lung liquid removal in newborn lambs; (5) to compare cation transport in lung epithelial cells harvested from preterm lambs, with and without preceding respiratory distress; (6) to see if granulocytes contribute to the abnormal lung vascular protein permeability associated with respiratory distress in preterm lambs; and (7) to test the efficacy of surfactant replacement in preventing or attenuating the lung endothelial injury that occurs in lambs after premature birth. Pulmonary edema is an important component of many types of newborn lung disease. The proposed work should help to clarify how these conditions develop and by what means they can be managed most effectively.