Studies of surfactant function and metabolism are necessarily complex because of the multicomponent lipid and protein nature of surfactant and the multiple form transitions, inactivation, and recycling events that occur in the alveolus. The projects in this grant are designed to answer questions about surfactant component metabolism and function in a clinically relevant model of respiratory distress syndrome (RDS) - surfactant treated preterm lambs. The hypothesis is that quantitative and integrated measurements of surfactant component metabolism and function will provide information to optimize surfactant therapy for RDS. Radiolabeled precursors of the lipophilic surfactant proteins SP-B and SP- C will be used to measure the lamellar body accumulation and secretion kinetics of the proteins. The alveolar clearance, lamellar body association, and lung clearance of SP-B and SP-C will be measured in preterm ventilated lambs treated with surfactants selected to evaluate the interactions of SP-A, SP-B, and SP-C. These measurements with the surfactant proteins will be made in parallel with labeled dipalmitoylphosphatidylcholine (DPPC) to permit the direct comparison of DPPC and surfactant protein metabolism. Because surfactant responses in animal models vary depending on style of ventilation and clinical responses, we will test the hypothesis that ventilation style alters surfactant function and metabolism. Surfactant from the different ventilation groups will be analyzed for physical and form conversion characteristics and function. Surfactant phospholipid, protein and mRNA metabolism will be evaluated in relation to ventilation style. This information combined with the measurements of surfactant function from samples collected from the SP-B and SP-C metabolism studies will provide a uniquely integrated evaluation of surfactant within the preterm lung with RDS.
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