Pleural Liquid Exchange and Lung Mechanics

描述（由申请人提供）：本研究的目的是研究导致胸腔积液形成的一些因素。胸膜液的主要功能是在呼吸时对胸膜表面进行润滑。因此，了解胸腔积液在胸腔间隙形成和清除的机制，对于了解诸如胸腔积液和胸腔粘连等疾病的发病机制具有重要意义。我们最近对切除的大鼠横膈膜的研究显示出与胸膜和其他间质膜相似的运输特性，并表明部分胸膜液可能通过横膈膜从腹膜腔流出。其他研究人员的研究表明，液体和蛋白质的活跃间皮运输的作用。这一建议侧重于两个方面。其一是相对于来自微循环的贡献，来自腹膜腔的胸膜液体和蛋白质通过隔膜的贡献。在清醒的大鼠中测量放射性示踪白蛋白从循环进入胸膜间隙、横膈膜和腹膜腔的运输。其他实验将研究从腹膜腔到横膈膜、循环和胸膜间隙的运输。高血压对转运的影响将在自发性高血压大鼠及其遗传正常血压对照Wistar-Kyoto大鼠中进行研究。第二个研究领域涉及液体和蛋白质通过胸膜的主动运输相对于通过扩散和体积流的被动运输的贡献。心包膜和横膈膜将被研究，因为这些组织是独立的，不像在体外研究中需要剥离的内脏和胸膜壁层。一个具体的目标是开发一种方法来分离心包和横膈膜的被动和主动运输特性，这两个组织都有间皮和间质。

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.