TRANSPORT ACROSS ALVEOLAR CAPILLARY MEMBRANE

本提案的主要目的是评估 发生在肺内皮和上皮通透性和血管 与毛细血管压力相关的阻力， 激活、补体激活（ZAP）和血小板激活 因子和百草枯通过循环的挑战。 肺 水肿可能是由于毛细血管异常渗漏， 血浆蛋白和/或毛细血管压力升高。 我们 选择这些挑战是因为它们产生强烈的 血管收缩，血小板活化因子除外 放松大鼠的肺循环，肺水肿， 部分病例内皮细胞受损。 我们将评估 抗氧化剂（例如，超氧化物歧化酶，过氧化氢酶，异丙嗪， 和DPPD），α和β肾上腺素化合物（例如， 去甲肾上腺素、异丙肾上腺素）、乙酰胆碱、花生四烯酸 系统（血栓素合成酶抑制剂），组胺阻滞剂 （苯海拉明和西咪替丁）在离体大鼠、犬和豚鼠肺中的作用 面对这些挑战。 我们将测量大的， 动脉和静脉阻力和顺应性较小，沿着 正常和受损肺部的毛细血管压力，以确定 α、β H1、H2和AA的各种成分 系统改变每个隔室中的阻力和顺应性。 此外，我们还将评估一个重要的渗透性 参数，渗透率表面积产品使用前节点 淋巴引流开胸犬准备，以确定这一点 6种内源性血浆蛋白的膜溶质参数。 此外，我们将测量单向白蛋白通量通过 离体肺中的内皮屏障，以确定通量是否是 在两个方向上都是一样的，无论这些通量是否 在缺氧和不同形式的肺损伤中改变。 最后我们 将评估肺泡的渗透性 PMA、ZAP、血小板活化激发的肺中的膜 因子或百草枯，以确定这一重要膜的作用 在肺水肿的发展中起作用。

The major aim of this proposal is to evaluate the changes which occur in lung endothelial and epithelial permeability and vascular resistances as related to capillary pressures, following neutrophil activation, complement activation (ZAP), and platelet activating factor and paraquat challenges via the circulation. Pulmonary edema can result because capillaries are abnormally leaky to plasma proteins and/or capillary pressure is elevated. We selected these challenges because they produce intense vasoconstriction,, with the exception of platelet activating factor which relaxes rat pulmonary circulation, pulmonary edema, and in some cases damaged endothelium. We will evaluate the effects of antioxidants (e.g., superoxide dismutase, catalase, promethazine, and DPPD), alpha and beta adrenergenic compounds (e.g., norepinephrine, isoproterenol), acetylcholine, arachidonic acid system (thromboxane synthetase inhibitor), histamine blockers (benadryl and cimetidine) in isolated rat, dog and guinea pig lungs subjected to these challenges. We will measure the large and small arterial and, venous resistances and compliances, along with capillary pressures in normal and damaged lungs to determine how the various components of the alpha, beta H1, H2, and AA systems alter resistances and compliances in each compartment. In addition, we will also evaluate an important permeability parameter, the permeability surface area product using prenodal lymph draining an open-chested dog preparation to determine this membrane-solute parameter for 6 endogenous plasma proteins. Also, we will measure unidirectional albumin fluxes across the endothelial barrier in isolated lungs to determine if the flux is the same in both directions, and whether or not these fluxes are altered in hypoxia and different forms lung damage. Finally, we will evaluate the permeability properties of the alveolar membrane in lungs challenged with PMA, ZAP, platelet activating factor or paraquat to determine the role this important membrane plays in the development of pulmonary edema.