PULMONARY EPITHELIAL PERMEABILITY AND ALVEOLAR EDEMA

肺上皮通透性和肺泡水肿

• 批准号: 3347509
• 负责人: BARRY T PETERSON
• 金额: $ 9.75万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3347509
• 关键词: adult respiratory distress syndrome; disease /disorder model; electron microscopy; histochemistry /cytochemistry; lung alveolus; mathematical model; membrane permeability; noninvasive diagnosis; oleate; pulmonary edema; radiotracer; respiratory disorder diagnosis; respiratory epithelium; solute; technetium

This study will use nuclear imaging techniques, analysis of lung lymph, and in vivo electron dense tracers to examine trans- epithelial movement of solutes among the air, interstitial, and vascular spaces of the lungs of anesthetized sheep. The relationship between the site of solute movement through the epithelium and alveolar edema will also be studied. Our studies to date show that nuclear imaging of aerosolized 99Tc-labeled albumin clearance may be a valuable technique for detecting changes in epithelial permeability because it is non- invasive, appears to be sensitive to lung injury, and its clearance rate is unaffected by changes in lung volume. To further evaluate this technique, pulmonary and systemic lymph will be collected to monitor the appearance of the albumin in the interstitial spaces. We will compare labeled albumin to the currently popular 99Tc- DTPA (diethylenetriamine pentaacetate) for detecting physiologically relevant increases in pulmonary epithelial permeability by measuring their clearances from the lungs of sheep with lung injury induced by intravenous infusions of air or oleic acid. We will also measure the effects of increases in lymph flow and alterations in the distribution of blood flow to the tissue on the clearance of labeled albumin. To determine if the site of solute clearance is through the alveolar or extra-alveolar epithelium, colloidal gold or horseradish peroxidase will be instilled in the airspaces of anesthetized sheep that receive intravenous oleic acid and lung tissue samples will be examined under an electron microscope. Additional sheep will receive one of the tracers intravenously during the development of oleic acid-induced alveolar edema to determine if the pathways for solute clearance are the same as those through which circulating solutes enter the airways during alveolar flooding. These studies on the measurement of increased epithelial permeability and the routes of solute movement during alveolar flooding will aid in the development of improved methods for the detection, prevention and treatment of alveolar edema.

本研究将利用核成像技术，分析肺 淋巴和体内电子密度示踪剂，以检查反式- 溶质在空气、间质和 麻醉绵羊肺的血管空间。 的 溶质运动的位置之间的关系 还将研究上皮和肺泡水肿。 我们迄今为止的研究表明， 99 Tc标记的白蛋白清除可能是一种有价值的技术， 检测上皮渗透性的变化，因为它是非- 侵入性，似乎对肺损伤敏感，其清除 心率不受肺容量变化的影响。 为了进一步评估 将收集肺和全身淋巴液， 监测白蛋白在间隙中的出现。 我们将比较标记的白蛋白与目前流行的99 Tc- DTPA（二乙烯三胺五乙酸酯）检测 肺上皮细胞的生理相关增加 通过测量它们从肺部的清除率， 静脉输注空气或 油酸 我们还将测量淋巴细胞增加的影响， 流动和组织血流分布的改变 对标记白蛋白清除率的影响。 为了确定溶质清除的部位是否通过 肺泡或肺泡外上皮，胶体金或辣根 将过氧化物酶滴注到麻醉绵羊的空气中 接受静脉注射油酸和肺组织样本的患者， 在电子显微镜下观察。 更多的羊将 在发育过程中静脉注射一种示踪剂 油酸引起的肺泡水肿，以确定 对于溶质清除率， 循环溶质在肺泡溢流期间进入气道。 这些关于测量增加的上皮细胞的研究 渗透性和溶质运动的途径在肺泡 洪水将有助于开发改进的方法， 肺泡水肿的检测、预防和治疗。