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FLUID PRESSURE AND EXCLUDED VOLUMES IN LUNG

肺内的流体压力和排除容积

基本信息

批准号：
3337765
负责人：
JAMES Courtney PARKER
金额：
$ 12.28万
依托单位：
UNIVERSITY OF SOUTH ALABAMA
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-08-01 至 1994-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3337765
关键词：
body fluid osmolarity dogs histamine hydrostatic pressure isolation perfusion laboratory rabbit lactate dehydrogenases lung alveolus neutrophil protein transport pulmonary circulation pulmonary edema respiratory airway volume vascular endothelium permeability

项目摘要

Although there is general agreement that pulmonary capillaries restrict passage of proteins based on their size the selectivity properties of capillaries for differently charged macromolecules are more controversial. Tissue uptake and electron micrograph studies support a negative barrier hypothesis while acute lymph studies indicate a positive capillary barrier. We have proposed an interstitial cation exchange mechanism based on interstitial distribution studies of lactate dehydrogenase (LDH) isozymes which appears to reconcile these two positions. In the proposed research we will specifically characterize pulmonary endothelial permeability in terms of permeability-surface area products (PS) and reflection coefficients (sigma) for two globular proteins LDH 1 (pI=5.0) and LDH 5 (pI=7.9), which have the same molecular weight (140,000 MW) but different net charges at blood pH. Tissue clearances of LDH and in vivo osmotic pressures of negative and neutral dextrans will be used to minimize the effect of interstitial fixed negative charges on transport data. These studies should reveal the magnitude and surface charge of the endothelial layer itself. We will also determine how the interstitial and basement membrane charged groups affect the backward egress of anionic and cationic LDH isozymes from the interstitium across the capillaries and also from interstitium into pulmonary lymph. In addition, we will measure the transport rates of LDH isozymes across the airway epithelium into lymph and plasma. The role of polycation infusion (protamine sulphate, the charge on plasma colloids, and serum permeability factors in charge related permselectivity and overall microvascular protein and water permeability will also be studied. Because chemotaxis and activation of polymorphonuclear leukocytes (PMNs) appears to be charge related, the effects of polycation dose and polyanion intervention on PMN induced microvascular damage will be studied. These data should allow separation of charge permselectivity between solute and pore from interstitial charge effects, direct endothelial damage due to polycations, and PMN induced capillary damage caused by polycations. A second focus is a further characterization of pulmonary interstitial fluid conductance during oleic acid injury and at increased transpulmonary pressures.

尽管人们普遍认为肺毛细血管根据蛋白质的大小和选择性限制蛋白质的通过不同电荷大分子的毛细管性质更具争议性。组织摄取与电子显微照片研究支持负屏障假说，而急性淋巴研究表明，存在正的毛细血管屏障。我们已经提出了一个基于间隙的间隙阳离子交换机制乳酸脱氢酶(LDH)同工酶的分布研究这似乎调和了这两种立场。在建议的我们将专门研究肺内皮细胞的特征以渗透率表示的渗透率-表面积乘积(PS) 和两种球形蛋白LDH的反射系数(Sigma) 1(pI=5.0)和LDH 5(pI=7.9)，具有相同的分子重量(140,000兆瓦)，但在血液pH值下净电荷不同。乳酸脱氢酶的组织清晰度和体内渗透压将使用负性和中性的右旋糖苷将影响降至最低关于运输数据的间隙固定负电荷。这些研究应该揭示这些物质的大小和表面电荷。内皮层本身。我们还将确定如何间质和基底膜带电基团影响阴阳离子乳酸脱氢酶同工酶的反向流出穿过毛细血管的间质，也从间质进入肺淋巴。此外，我们还将测量交通乳酸脱氢酶同工酶穿过呼吸道上皮进入淋巴的比率和血浆。多聚阳离子输注(硫酸鱼精蛋白，血浆胶体电荷和血清通透性因子电荷相关通透性与总微血管蛋白此外，还将研究透水性能。因为趋化性出现多形核白细胞(PMN)活化与电荷有关，聚阳离子剂量和聚阴离子的影响将对PMN诱导的微血管损伤进行干预学习。这些数据应允许分离电荷间隙电荷在溶质与孔道之间的渗透选择性聚阳离子引起的直接内皮损伤和中性粒细胞聚阳离子引起的毛细血管损伤。第二个焦点是肺间质积液的进一步特征油酸损伤和AT升高时的电导经肺压力。