Pleural Liquid Exchange and Lung Mechanics

描述（由申请人提供）：本研究的目的是研究有助于胸膜液形成的一些因素。胸膜液的主要功能是在呼吸期间润滑胸膜表面。因此，胸膜腔液体形成和清除的机制对于理解疾病的发病机制是重要的，例如胸腔积液和胸膜粘连。我们最近在离体大鼠膈肌的研究表明，类似于胸膜和其他间质膜的运输特性，并建议部分胸膜液可能来自腹膜腔通过隔膜。其他研究人员的研究表明，间皮细胞对液体和蛋白质的主动运输起着重要作用。这项建议侧重于两个领域。一个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经由隔膜的贡献。将在清醒大鼠中测量放射性示踪剂白蛋白从循环转运至胸膜腔、横膈膜和腹腔的情况。其他实验将研究从腹膜腔到隔膜、循环和胸膜腔的运输。将使用自发性高血压大鼠及其遗传性血压正常对照大鼠（Wistar-Kyoto大鼠）研究高血压对转运的影响。第二个研究领域涉及液体和蛋白质通过胸膜的主动转运相对于通过扩散和整体流动的被动转运的贡献。将研究心包膜和隔膜，因为这些组织是独立的，不像体外研究需要剥离的内脏和壁层胸膜。一个具体的目标是开发一种方法来分离心包和隔膜的被动和主动运输特性，组织具有间皮和间皮。

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.