The surface of pulmonary alveoli is lined by an acellular material, the components of which have been termed the pulmonary surfactant system. A monomolecular film which is formed at the air/liquid interface from phospholipids, primarily dipalmitoylphospha- tidylcholine, and perhaps other components of the acellular hypophase, is responsible for stability of the airspaces and normal lung function. The biochemical and physiological development of several constituents of the surfactant system have been character- ized from the immature fetal through the adult state. Up to this point, however, investigations of biophysical mechanisms responsible for formation and ultimate function of the monomolecular film have been restricted in their scope by analytical methods presently available. This restriction is reflected in the interpretations of the roles of the hypophase and interface, and their molecular interactions, on lung function in situ. A better understanding of the relevance of intermolecular dynamics to lung function during development of the monolayer from the bulk hypophase, composition of the film and interactions between the film and hypophase. This information is most relevant to such questions as pathophysiology of disease states in which the surfactant system is compromised and for assessment of therapeutic agents that might be used to treat such states, e.g., neonatal and adult respiratory distress syndrome. We plan to study the interactions of lipids and proteins during development of the surfactant system and the effect of these interactions on lung function. Evaluation of the temperature dependence of mechanical responses via volume-pressure (V-P) diagram will be combined with physical analyses of the surfactant system. The physical analyses will be performed on fractionated and reconstituted surface active material (SAM) isolated from lungs after V-P analysis. The physical techniques used to study SAM are Fourier-Transform-Infrared (FT-IR) spectroscopy and a new method to analyze surface properties. Both physical techniques have been successfully used by the principal investigator in preliminary studies of SAM. These methods, though routine to other lipid-pro- tein systems, are unique to study of the surfactant system. Assessment of developmental aspects of molecular interactions in SAM from fetal through adult life will be made. Subjects will include immature and mature fetal, newborn, and adult rabbits. The resulting information will be useful in understanding development of component interaction within the surfactant system as related to lung function.
