The long term goal of this research is to determine the mechanical factors affecting pleural liquid exchange. These factors are important to the understanding of the etiology and pathogenesis of pleural effusions and to the efficient lubrication of the pleural surfaces during ventilation. This research is focused on two factors: ventilation and microvascular pressure. The first part of this proposal concerns the effect of ventilation on pleural liquid filtration. The hypothesis is that ventilation increases the rate of pleural liquid filtration through changes in pleural/capillary membrane permeability caused by increases in lung sliding-induced shear stress. Pleural liquid filtration will be measured in a rabbit model. Evan's blue dyed albumin will be used as the tracer. Fluorescence videomicroscopy will be used to measure the concentration of Evan's blue dyed albumin. The ratio of the tracer in pleural liquid to that in plasma (Cl/Cp) will be measured at several time periods after injection of the tracer to produce a Cl/Cp vs time curve. The effect of increased ventilation caused by breathing a CO2- air mixture on the Cl/Cp vs time curve will be studied. An upward shift in the Cl/Cp vs time curve with increased ventilation will indicate an increase in both the pleural filtration rate and membrane permeability. A mathematical analysis will be used to quantify the change in filtration rate with ventilation. To show the relationship between the lung sliding velocity-induced shear stress and the pleural filtration rate, the regional variation of lung surface velocity and pleural liquid thickness will be measured during mechanical ventilation. The induced shear stress due to lung sliding, proportional to velocity divided by thickness, will be correlated to the spatial distribution of Evan's blue dye albumin in the parietal pleural membrane of the chest wall. The second part of the proposal concerns the effect of microvascular pressure on pleural liquid exchange. A previous study from this laboratory has shown in chronically hypertensive rats (SHR) a decreased pleural protein concentration and an increased pleural space thickness compared to control normotensive rats. This suggests that the SHR has a higher capillary pressure and higher filtration rate. To test this hypothesis, microvascular pressure in pleural capillaries will be measured by the micropuncture technique and the pleural filtration rate by the movement of Evan's blue dyed albumin from the blood into the pleural space.
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