PERINATAL PULMONARY MICROCIRCULATION AND LUNG FLUID

本提案的总体目的是增进了解 肺微循环和肺液体平衡的变化 和出生后。 该项目包括研究， 肺微血管压力的发育差异 和蛋白质渗透性，参与的途径和机制 产前和产后肺腔液体清除率， 肺微血管损伤的发病机制及防治 与早产有关。 肺血流动力学，肺 液体过滤和微血管蛋白渗透性将 通过各种实验方法在胎儿和新生羔羊中进行评估 方法，包括测量肺淋巴流量和淋巴 蛋白质清除率，肺泡直接微穿刺法 液体和肺微血管压力，指示剂稀释 研究以量化肺腔液体体积的变化， 时间，重量法测定肺含水量， 肺上皮细胞离子转运的体外研究。 具体目标 （1）比较肺微血管蛋白通透性， 未麻醉的早产和足月胎羊，通过评估其 肺血管和淋巴流对快速静脉注射的反应 生理盐水输注和左心房压力升高;（2）通过 潜在空气空间中的直接微穿刺液体压力， 肺表面的小肺动脉和小静脉， 有和没有空气膨胀，在活胎羔羊;（3）， 确定胸膜间隙作为以下途径的重要性： 胎羊和新生羔羊肺泡液体清除率;（4）观察 低蛋白血症减慢新生羔羊的肺液体排出;（5） 比较收集的肺上皮细胞中的阳离子转运 来自早产羔羊，有和无先前呼吸道感染 痛苦;（6）看看粒细胞是否有助于异常肺 与呼吸窘迫相关的血管蛋白渗透性 在早产羔羊中;和（7）测试表面活性剂的功效 预防或减轻肺内皮细胞 羔羊早产后发生的损伤。 肺 水肿是许多类型新生儿肺的重要组成部分 疾病 拟议的工作应有助于澄清这些 条件的发展，并通过什么手段，他们可以管理最 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.