PLEURAL LIQUID EXCHANGE AND LUNG MECHANICS

本研究的长期目标是确定影响胸腔积液交换和胸膜润滑的机械因素。本研究主要研究三个因素：通气量、胸液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在呼吸过程中胸膜表面的有效润滑是很重要的。这项建议的第一部分涉及胸腔积液容量对呼吸机引起的胸腔积液剪切力增加的影响。假设胸腔积液容量的增加会增加通气性胸腔积液的厚度，从而导致胸腔积液剪切力降低(与肺速除以胸腔积液厚度成正比)。胸腔积液厚度随着胸腔积液体积的增加而增加，随着呼气末肺活量的增加而减小。通过胸膜窗口对染色的胸液进行荧光成像，测量胸腔积液厚度。肺的相对速度将从肺运动的视频图像中测量。通过测量胸水和胸膜表面的透明质酸浓度来评估剪应力引起的胸膜边界润滑的变化。这项建议的第二部分涉及胸膜的过滤性能，使用体外测量水力传导性、白蛋白反射系数和白蛋白扩散系数。由于先前对剥离的壁层和内脏胸膜的研究受到了质疑，因此将对心包膜、纵隔膜和横隔膜中央肌腱进行研究，因为这些组织无需剥离即可分离。假说是胸膜内衬间皮细胞不会限制大分子的通过，就像以前对兔肠系膜的研究中所测量的那样。

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.