X-ray diffraction studies of bulk replacement lung surfactants: Implications for surfactant failure in Adult Respiratory Distress Syndrome

COLL 375

Heidi E. Warriner1, An Ngo1, H. William Taeusch2, and Joseph A. Zasadzinski3. (1) Chemistry, University of Pittsburgh, 219 Parkman Avenue, CSC 234, Pittsburgh, PA 15260, (2) Pediatrics and Physiology & the Cardiovascular Research Institute, University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110, (3) Department of Chemical Engineering, University of Califirnia, Santa Barbara, Santa Barbara, CA 93106-5080
Human lung surfactant is a complex mixture of lipids and peptides which reduces pulmonary surface tension, enabling normal breathing. Lack of effective surfactant results in the potentially fatal condition of Respiratory Distress Syndrome (RDS). RDS patients can usefully be separated into two patient classes: (1) premature infants with immature surfactant production pathways and (2) adults suffering from pulmonary infection or trauma. While replacement lung surfactant (RLS) therapy has revolutionized neonatal RDS treatment, excess serum protein in the adult RDS lung tends to inactivate lung surfactants. However, recent in vivo and in vitro experiments have shown that small amounts of low molecular weight PEG or dextran can markedly improve the performance of current commercial replacement surfactants. We present small-angle x-ray scattering data of clinically employed replacement surfactants in the presence of both inhibitory concentrations of serum proteins and low molecular weight polymer. The structural motifs revealed are compared with current theories of surfactant action and failure in the adult RDS lung.