and Specific Aims.) The overall objective of this application is to identify new mechanisms responsible for removal of excess fluid from the distal airspace of the lung. In this application, Specific Aim 1 will test the hypothesis that endogenous release of catecholamines will increase alveolar epithelial sodium transport and net alveolar liquid clearance under specific pathologic conditions. Confirmation of this hypothesis would identify a previously unrecognized safety mechanism which can protect the lung against alveolar flooding as well as the mechanism to hasten the resolution of alveolar edema once flooding of the distal airspaces has occurred.
Specific Aim 2 will determine the mechanisms responsible for the marked decrease in alveolar epithelial liquid clearance that occurs following short (2h) or long term (24h) atelectasis, even in the presence of normal pulmonary blood flow. Since microatelectasis is common in various acute lung injury syndromes, the mechanism for the decrease in alveolar liquid clearance (alveolar hypoxia versus loss of alveolar volume itself) has scientific and clinical implications. Finally, in spite of our new knowledge regarding the role of sodium transport in alveolar fluid clearance, no information is available regarding the pathway for alveolar water clearance. Based on promising preliminary studies of water transport across alveolar epithelium, experiments are proposed in Specific Aim 3 to determine the role of cell membrane water transport channels on both type I and type II alveolar epithelial cells for the removal of water from the distal airspaces of the lung.
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