PULMONARY EPITHELIAL PERMEABILITY AND ALVEOLAR EDEMA

本研究将使用核成像技术，对肺部进行分析 淋巴和体内电子密度示踪剂来检查反式 溶质在空气、间质和 麻醉绵羊肺的血管间隙。这个 溶质在不同温度下运动的位置之间的关系 上皮细胞和肺泡水肿也将被研究。 到目前为止，我们的研究表明，气雾化的核成像 99Tc标记的白蛋白清除可能是一项有价值的技术 检测上皮通透性的变化，因为它是非 侵袭性，似乎对肺损伤很敏感，其清除 心率不受肺容量变化的影响。进一步评估 这项技术，肺和全身淋巴将被收集到 监测白蛋白在间质中的出现情况。 我们会将标记的白蛋白与目前流行的99TC- 检测用二乙三胺五乙酸二乙酯 肺上皮细胞生理性增加 通过测量它们从肺中清除的通透性 静脉输注空气或空气致绵羊肺损伤 油酸。我们还将测量淋巴增加的影响。 流向组织的血液流动和分布的变化 对标记白蛋白的清除作用。 以确定溶质清除的位置是否通过 肺泡或肺泡外上皮、胶体金或辣根 过氧化物酶将被注入麻醉绵羊的空气中 接受静脉注射油酸和肺组织样本的人将 在电子显微镜下检查。更多的绵羊将 在发育过程中静脉注射其中一种示踪剂 以确定油酸诱导的肺泡水肿途径是否 对于溶质清除，与通过 在肺泡泛滥期间，循环的溶质进入呼吸道。 增生性上皮细胞测定的研究 肺泡通透性与溶质运移途径 淹水将有助于开发更好的方法来 肺泡水肿的检测与防治。

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.