PLEURAL LIQUID EXCHANGE AND LUNG MECHANICS

本研究的长期目标是确定影响胸膜液体交换和胸膜润滑的力学因素。本研究的重点是三个因素：通气，胸膜液容量和边界润滑剂透明质酸。这些因素对于了解胸腔积液的病因和发病机制以及通气过程中胸腔表面的有效润滑具有重要意义。本文第一部分讨论了胸腔液体积对通气引起的胸腔液剪应力增加的影响。假设胸腔积液量的增加会增加通气时的胸腔积液厚度，从而导致胸腔积液剪切应力的减小（与肺速度除以胸腔积液厚度成正比）。胸膜液厚度随胸膜液容量的增加而增加，随呼气末肺容量的增加而减少。通过胸膜窗对染色的胸膜液进行荧光成像，测量胸膜液的厚度。肺相对速度将通过肺运动的视频图像来测量。剪应力引起的胸膜边界润滑变化将通过测量胸膜液和胸膜表面的透明质酸浓度来评价。本提案的第二部分是关于胸膜的过滤特性，使用体外测量的水力传导性，白蛋白反射系数和白蛋白扩散系数。由于先前对剥离的胸膜壁层和内脏胸膜的研究受到质疑，因此我们将对心包膜、纵隔膜和膈中央肌腱进行研究，因为这些组织可以在不剥离的情况下分离。假设是内衬间皮细胞的胸膜不限制大分子的通过，正如先前对兔肠系膜的研究所测量的那样。

The long term goal of this research is to determine the mechanical factors affecting pleural liquid exchange and pleural membrane lubrication. This research is focused on three factors: ventilation, pleural liquid volume and the boundary lubricant hyaluronan. These factors are important to understanding the etiology and pathogenesis of pleural effusions and the efficient lubrication of the pleural surfaces during ventilation. The first part of this proposal concerns the effect of pleural liquid volume on the ventilation-induced increase in pleural liquid shear stress. The hypothesis is that an increase in pleural liquid volume will increase pleural liquid thickness with ventilation and thus cause a reduced pleural liquid shear stress (proportional to lung velocity divided by pleural liquid thickness). Pleural liquid thickness will increase with increasing pleural liquid volume and decrease with increasing end-expiratory lung volume. Pleural liquid thickness will be measured by fluorescent imaging of the dyed pleural liquid through a pleural window. Lung relative velocity will be measured from videoimages of lung motion. The shear stress- induced change in pleural boundary lubrication will be evaluated by measuring hyaluronan concentration in pleural liquid and on pleural surfaces. The second part of this proposal concerns the filtration properties of pleural membrane using in vitro measurements of hydraulic conductivity, albumin reflection coefficient and albumin diffusion coefficient. Since previous studies of stripped parietal and visceral pleurae have been questioned, the pericardial membrane, mediastinal membrane, and diaphragm central tendon will be studied as these tissues can be isolated without stripping. The hypothesis is that pleural membrane lined with mesothelial cells does not restrict the passage of macromolecules, as measured in previous studies of rabbit mesentery.