Inactivation of pulmonary surfactant and its prevention

Sammanfattning: Pulmonary surfactant is a lipoprotein complex coating the conducting airways down to the terminal airspaces. Its main function is to lower surface tension at the air liquid interface thus preventing alveolar collapse at end expiration. Primary surfactant deficiency is the main cause of neonatal respiratory distress syndrome (RDS) and treatment with exogenous pulmonary surfactant improves the course of the disease significantly. Furthermore, secondary surfactant deficiency caused by inactivation of endogenous surfactant occurs in older patients with acute RDS (ARDS), pneumonia or meconium aspiration syndrome (MAS). Abnormal alveolar presence of substances like aspirated meconium or leaking serum proteins inhibits surface activity. This inactivation of endogenous surfactant can be overcome by increasing the surfactant concentration with exogenous surfactant. In the clinical setting modified natural surfactants extracted from animal lungs are used most commonly. However, a new generation of surfactant preparations containing synthetic proteins are currently under development to improve supply and to lower costs. In our project we investigated the sensitivity of exogenous surfactant preparations to different types of inactivation and tried to find ways for improving their resistance. In vitro we found new synthetic surfactant containing proteins to be more resistant to meconium inactivation than modified natural surfactants. Meconium induced inactivation of modified natural surfactant was reversible, especially in the presence of calcium or polymyxin B (PxB), a cross linking protein of phospholipid films with antimicrobial properties. PxB enriched surfactant also preserves antibiotic characteristics in vitro and in an animal model of neonatal pneumonia. Accidentally, we observed surfactant inactivation by silicone oil dissolved from syringes that are in clinical use. This type of inactivation may lead to significant deterioration of lungs in an animal model of RDS. By comparison of surfactant preparations comprising the hydrophobic surfactant protein B and/or C we pointed out that both proteins are needed for alveolar stability.