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.
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