Pulmonary vascular injury, which alters cellular dynamics and fluid transport properties, is a primary event leading to the development of edema in Adult Respiratory Distress Syndrome. The overall objective of this proposed interdisciplinary project (Biochemistry, Immunology, and Physiology) is to understand key pathophysiologic mechanisms of edematous lung injury by directly measuring the effect of altered microvascular pressure, membrane surface area, and vascular permeability. Experiments are designed to gain quantitative information on the effect that free radicals, key vasoactive mediators, and activated neutrophils have on transvascular fluid and protein flux in the early phase of edematous lung injury. The investigation will test the following hypothesis: that vasoactive mediators alter transvascular flux by selectively increasing pressure, while free radicals preferentially increase membrane permeability. To test our hypothesis we plan to use a unique combination of proven techniques to concomitantly measure mean microvascular pressure (double occlusion method), filtration surface area (direct microscopic observation), and capillary permeability (indicator dilution method) in the isolated perfused rat lung model. The importance of the research is three-fold. First, this investigation will provide new quantitative information about key mechanisms involved in the pathogenesis of vascular injury which is a major cause leading Adult Respiratory Distress Syndrome. Second, these studies provide proved new information on the mechanisms-of-action of activated neutrophils, free radicals, and vasoactive mediators by pinpointing their effects on microvascular pressure, membrane surface area, and capillary permeability. Third, our studies will identify early markers associated with the pathophysiologic processes of pulmonary edema formation. The latter is of particular importance since information gained from these studies will permit explorations of new therapeutic approaches in the treatment and prevention of pulmonary edema.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036745-03
Application #
3351965
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Patterson, C E; Jin, N; Packer, C S et al. (1992) Activated neutrophils alter contractile properties of the pulmonary artery. Am J Respir Cell Mol Biol 6:260-9
Patterson, C E; Rhoades, R A; Garcia, J G (1992) Evans blue dye as a marker of albumin clearance in cultured endothelial monolayer and isolated lung. J Appl Physiol 72:865-73
Bennie, R E; Packer, C S; Powell, D R et al. (1991) Biphasic contractile response of pulmonary artery to hypoxia. Am J Physiol 261:L156-63
Jin, N; Packer, C S; Rhoades, R A (1991) Platelet activating factor causes relaxation of isolated pulmonary artery and aorta. Adv Exp Med Biol 304:517-22
Roepke, J E; Patterson, C E; Packer, C S et al. (1991) Response of perfused lung and isolated pulmonary artery to adenosine. Exp Lung Res 17:25-37
Jin, N; Packer, C S; Rhoades, R A (1991) Reactive oxygen-mediated contraction in pulmonary arterial smooth muscle: cellular mechanisms. Can J Physiol Pharmacol 69:383-8
Rhoades, R A; Packer, C S; Roepke, D A et al. (1990) Reactive oxygen species alter contractile properties of pulmonary arterial smooth muscle. Can J Physiol Pharmacol 68:1581-9
Patterson, C E; Barnard, J W; Lafuze, J E et al. (1989) The role of activation of neutrophils and microvascular pressure in acute pulmonary edema. Am Rev Respir Dis 140:1052-62
Barnard, J W; Patterson, C E; Hull, M T et al. (1989) Role of microvascular pressure in reactive oxygen-induced lung edema. J Appl Physiol 66:1486-93

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