Pleural Liquid Exchange and Lung Mechanics

描述(申请人提供)：本研究的目的是研究导致胸腔积液形成的一些因素。胸腔积液的主要功能是在呼吸过程中对胸膜表面进行润滑。因此，胸腔积液形成和排出的机制对于了解诸如胸腔积液和胸膜粘连等疾病的发病机制非常重要。我们最近在切除的大鼠横隔膜上的研究显示了与胸膜和其他间质膜相似的转运特性，并提示部分胸腔积液可能是通过横隔膜从腹膜中产生的。其他研究人员的研究表明，液体和蛋白质的主动间皮运输也起到了作用。这项建议主要集中在两个方面。一种是腹膜对胸液和蛋白质的贡献，相对微循环的贡献。将在清醒大鼠中测量放射性示踪剂白蛋白从循环进入胸腔、横隔膜和腹膜的转运。其他实验将研究从腹膜腔到横隔膜、循环和胸膜的运输。高血压对运输的影响将使用自发性高血压大鼠及其基因正常血压对照Wistar-京都大鼠进行研究。第二个研究领域涉及通过胸膜主动运输液体和蛋白质相对于通过扩散和整体流动的被动运输的贡献。将对心包膜和隔膜进行研究，因为这些组织是自由站立的，而不像内脏和壁层胸膜需要剥离才能进行体外研究。一个特定的目标是开发一种方法来分离心包和横隔膜的被动和主动运输特性，心包和横隔膜是既有间皮又有间质的组织。

DESCRIPTION (provided by applicant): The goal of this research is to study some factors that contribute to the formation of pleural liquid. The primary function of pleural liquid is lubrication of the pleural surfaces during breathing. Thus the mechanisms by which pleural liquid is formed in and cleared from the pleural space are important to understanding the pathogenesis of diseases, such as pleural effusions and pleural adhesions. Our recent studies in the excised rat diaphragm showed transport properties similar to those of pleural and other interstitial membranes and suggested that part of the pleural liquid might be derived from the peritoneal cavity via the diaphragm. Studies by other investigators have suggested a role for active mesothelial transport of liquid and protein. This proposal focuses on two areas. One is the contribution to pleural liquid and protein from the peritoneal cavity via the diaphragm relative to the contribution from the microcirculation. The transport of radioactive tracer albumin from the circulation into the pleural space, diaphragm, and peritoneal cavity will be measured in conscious rats. Other experiments will study transport from the peritoneal cavity into the diaphragm, circulation and pleural space. The effect of hypertension on transport will be studied using spontaneously hypertensive rats and its genetic normotensive control, the Wistar-Kyoto rat. The second area of research deals with the contribution of active transport of liquid and protein across pleural membrane relative to passive transport by diffusion and bulk flow. The pericardial membrane and diaphragm will be studied because these tissues are free standing, unlike the visceral and parietal pleurae that need to be stripped for in vitro studies. A specific objective is to develop a method to separate passive from active transport properties of pericardium and diaphragm, tissues that have both mesothelium and interstitium.