The proposed research is designed to address five specific problems: (1) to characterize the relationship in the lung between the capillary filtration coefficient and the osmotic reflection coefficient, which describe the capillary permeability to fluid and proteins respectively, over a wide range of pulmonary microvascular permeabilities and further, to correlate these changes with the accumulation of alveolar fluid and protein; (2) to determine the effect of high intravascular pressures on the pulmonary osmotic reflection coefficient - the threshold for and reversibility of pressure-induced injury will be assessed, as well as the dependence of the injury on the duration of the pressure stress; (3) to determine whether prior injury to the lung predisposes the pulmonary microvasculature to pressure-induced permeability changes; (4) to determine whether pressure-induced injury is associated with redistribution of blood flow in the lung; and (5) to evaluate the gross anatomic sites of pressure-induced versus chemically-induced lung injury - are there gross leaks or tears in the alveolo-capillary barrier? Pulmonary microvascular permeability will be assessed by measuring the capillary filtration coefficient and the osmotic reflection coefficient, the latter using osmotic transients, protein vs. hematocrit fluid filtration volumes and lymphatic flux analysis. The ability of both the pulmonary capillary and the alveolar epithelial-capillary endothelial barriers to sieve proteins will be determined. These parameters will be assessed in isolated, blood perfused canine lung lobes. The effects of high intravascular pressures will be tested in normal lung lobes and in those with modest lung injury induced by oleic acid or complement fragments. Regional distributions of pulmonary blood flow before and after injury will be determined by the distribution of radiolabelled microspheres. Finally, acrylic corrosion casts using a low viscosity acrylic material, will be made of the pulmonary vasculature to evaluate the gross anatomic locus of pressure- and permeability-induced injuries.