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机械因素。 本研究主要关注三个因素：通气量、胸腔积液量和边界润滑剂透明质酸。 这些因素对于理解胸腔积液的病因和发病机制以及通气期间胸膜表面的有效润滑是重要的。 该建议的第一部分涉及胸膜液体体积对通气引起的胸膜液体切应力增加的影响。 假设胸膜液体体积的增加将随着通气而增加胸膜液体厚度，从而导致胸膜液体剪切应力降低（与肺速度除以胸膜液体厚度成比例）。 胸膜液体厚度将随着胸膜液体体积的增加而增加，并且随着呼气末肺体积的增加而减少。 通过胸膜窗对染色的胸膜液进行荧光成像，测量胸膜液厚度。 将从肺运动的视频图像测量肺相对速度。 将通过测量胸膜液和胸膜表面上的透明质酸浓度来评价胸膜边界润滑的剪切应力诱导的变化。 该建议的第二部分涉及使用体外测量的水力传导率，白蛋白反射系数和白蛋白扩散系数的胸膜的过滤特性。 由于先前对剥离的壁层和脏层胸膜的研究受到质疑，因此将研究心包膜、纵隔膜和膈肌中央腱，因为这些组织可以在不剥离的情况下分离。 假设是胸膜内衬间皮细胞不限制通过的大分子，在以前的研究中测量的兔肠系膜。

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.