LUNG EPITHELIAL ION TRANSPORT AFTER PREMATURE BIRTH

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Pulmonary edema is a consistent pathological feature of the neonatal respiratory distress syndrome and it occurs when fluid enters the, lung at a rate greater than the rate at which fluid is cleared. Pulmonary edema reduces lung volume, impairs oxygenation, and increases the need for respiratory support. Previous studies have clarified that respiratory failure after premature birth is associated with excess fluid and protein entry into the lung with resultant alveolar flooding. It is unclear whether delayed clearance of fluid from the lung is an additional factor contributing to lung edema in the neonatal respiratory distress syndrome. Because transepithelial ion movement is responsible, at least in part, for clearance of fluid from the distal airspace, we hypothesize that abnormal lung epithelial ion transport contributes to alveolar edema by delaying fluid clearance from the distal airspaces. Our long-term goal is to improve our understanding of the mechanisms that contribute to respiratory failure after premature birth. In this proposal, our studies will include assessment of transmembrane Na and Cl flux and Na-K-ATPase activity in distal lung epithelial cells as well as the molecular bases for alterations in ion transport. We plan to (l) define the mechanism by which neutrophils impair ion transport in lung epithelial cells; (2) characterize the changes in lung epithelial ion transport that are induced by pulmonary surfactant; (3) evaluate the role of nitric oxide in regulating Cl secretory function in lung epithelium around the time of premature birth; (4) determine if Na and Cl transport and Na-K-ATPase activity are abnormal in lung epithelial cells in the respiratory distress syndrome of prematurity; and (5) determine if surfactant replacement at birth favorably influences Na and Cl transport and Na-K-ATPase activity in lung epithelial cells. We predict that factors important in the pathogenesis of neonatal respiratory distress syndrome impair Na transport, decrease Na-K-ATPase activity, and promote postnatal Cl secretory activity. Our expectation is that a more complete understanding of the factors that contribute to pulmonary edema and respiratory failure after premature birth will improve our ability to design strategies and interventions that will reduce the severity of neonatal respiratory distress and diminish the adverse outcomes associated with this condition.