In this proposal, we plan to do a combination of basic and clinical studies aimed at better understanding of surfactant therapy of Respiratory Distress Syndrome of premature infants. 1. Surfactant proteins will be isolated and used to make simple protein/lipid surfactant mixtures. These mixtures will be tested by electron spin resonance spectroscopy, measurement of surface tension, and assessment of biological effects in animal models of surfactant deficiency. These studies will indicate how lipid and surfactant proteins interact at a molecular level and the consequences of this interaction on surfactant function in vitro and in vivo. 2. Using isolated surfactant proteins, we will use sensitive enzyme-linked imunosorbent assays to measure the major surfactant proteins in tracheal aspirates taken from the infants treated with surfactant. Using other ELISA's for protein inhibitors of surfactant function, we will test whether surfactant protein/inhibitor ratios measured on sequential tracheal aspirates correlate with response to surfactant therapy and results of pulmonary function testing. 3. We will carry out a series of clinical studies using protocols designed to investigate improved strategies for surfactant therapy of RDS. Infants will be studied by serial tests of functional residual capacity, conductance, time constants, compliance, and gas exchange. Serial measurements will be done to assess left to right shunting through a patient ductus arteriosus. We will define which infants are most likely to respond to treatment, which factors are associated with a suboptimal clinical responses, and which biochemical or physiological tests are most helpful in predicting responses. These studies should increase our understanding of this promising new therapy for premature infants.
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