TRANSPORT ACROSS ALVEOLAR CAPILLARY MEMBRANE

穿过肺泡毛细血管膜的运输

• 批准号: 3563697
• 负责人: AUBREY E. TAYLOR
• 金额: $ 17.73万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3563697
• 关键词: capillary; hydrostatic pressure; lung alveolus; membrane permeability; osmotic pressure; pulmonary edema; vascular endothelium permeability

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.

这项建议的主要目的是评估 发生在肺内皮细胞和上皮细胞的通透性和血管 中性粒细胞后的阻力与毛细血管压力有关 激活、补体激活(ZAP)和血小板激活 因子和百草枯通过循环挑战。肺 由于毛细血管异常渗漏，可导致水肿 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了激烈的 血管收缩，但血小板激活因子除外 它可以放松大鼠的肺循环，肺水肿，并在 部分病例内皮细胞受损。我们将评估这些措施的效果 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激素性化合物(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 (苯那君和西咪替丁)在大鼠、狗和豚鼠肺中的应用 受到这些挑战。我们将测量大的和 小的动脉和静脉阻力和顺应性，以及 以确定正常和受损肺的毛细血管压力 α、βH1、H2和AA的各种成分 系统改变每个隔间中的阻力和顺应性。 此外，我们还将评估一个重要的渗透率 参数，使用节前的渗透率表面积乘积 淋巴引流开胸狗的准备以确定这一点 6种内源性血浆蛋白的膜溶质参数。 此外，我们还将测量单向白蛋白通量 隔离肺内皮细胞屏障以确定该流量是否为 在两个方向上是相同的，无论这些通量是否 在缺氧和不同形式的肺损伤中发生改变。最后，我们 将评估肺泡的通透性 PMA、ZAP、血小板活化对肺膜功能的影响 决定作用的因素还是百草枯这个重要的膜 在肺水肿的发展过程中起着重要作用。