Evaluation of Surfactant Inhibition and Reactivation by Captive Bubble Surfactometry

Abstract

Pulmonary surfactant is a complex mixture of lipids and proteins, which forms a film at the air-water interface in the alveoli. Its main function is to lower the surface tension at this interface thus decreasing the work of breathing and preventing alveolar collapse. Dysfunction of surfactant in the lungs is associated with respiratory distress syndromes such as acute respiratory distress syndrome (ARDS) or meconium aspiration syndrome (MAS). Many substances have been described as inhibitory agents for pulmonary surfactant interfacial activity. Three of the most common in vivo are serum, cholesterol and meconium. The behaviour of surfactant films at the interface can be followed under physiologically relevant conditions in the Captive Bubble Surfactometer (CBS). This includes i) examination of rapid film formation by adsorption of surfactant into the interface of an air bubble, ii) monitoring re-adsorption of material from surface-associated reservoirs into the interface of the bubble upon expansion or iii) analysis of film dynamic properties during compression-expansion cycling of the interface. Using the CBS with a modified protocol that allows exposure of surfactant to high concentrations of inhibitory compounds, we have evaluated the effect of several agents on the biophysical properties of lung surfactant films under physiologically meaningful constraints. In this model assay, we observe significant differences in the interfacial performance of surfactant preparations in the presence or absence of inhibitory agents such as serum or meconium, which determine the importance of surfactant composition and structure on its susceptibility to inactivation. Moreover we have confirmed the higher resistance to inhibition of complexes of pulmonary surfactant with ionic and non-ionic polymers and the potential of these additives to design new therapeutic surfactant preparations.