Lining fluid flow and surfactant transport during the unsteady opening of pulmonary airways and alveoli

Tulane University, New Orleans LA

Investigators

Abstract

9978605 Gaver At birth, a newborn infant's lungs are liquid-filled and must be inflated from a collapsed state to initiate breathing. For healthy infants, a modest inspiratory effort introduces air into the lung so that the atmosphere can directly communicate with alveoli, the primary site of gas-exchange with blood. Gestationally mature lungs release surfactant that decreases the effort necessary to inflate the lung. However, premature infants may lack adequate surfactant, increasing the surface tension. Surfactant insufficiency coupled with the extremely small size of the lung results in a large inspiratory effort necessary to inflate the premature lung, leading to airway atelectasis (extensive collapse of portions of the lung), deranged pulmonary mechanical responses, poor ventilation/perfusion relationships and insufficient alveolar ventilation. These premature airways could be opened by high pressure from a mechanical ventilator, however this damages the sensitive epithelial cells that line the airway walls, resulting in respiratory distress syndrome (RDS). Surfactant replacement therapy (SRT), initiated in the late 1980's, has dramatically reduced the number of fatalities associated with this disease. Refinements in exogenous surfactant composition continue to improve the outcome of RDS infants. Nevertheless, RDS remains the fourth leading cause of death of premature infants in the United States. The goal of the proposed research is to develop integrated models of pulmonary mechanical behavior coupled to surfactant physicochemical interactions. We intend to take advantage of our understanding of surfactant physicochemical properties and fluid-structure interactions to identify surfactant properties that may protect the lung from RDS. Additionally, we will attempt to use the large disparity between surfactant adsorption and desorption rates and the creation of surfactant multi-layers to specify ventilation parameters that will actively enhance surfactant concentration and thus optimize the opening of pulmonary airways. We anticipate that these models will allow us to predict surfactant properties and ventilation scenarios that will be useful in improving the outcome of infants afflicted with RDS.