The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion
Publication of this article was funded by the Stellenbosch University Open Access Fund.
The original publication is available at http://www.dovepress.com/drug-design-development-and-therapy-journal
Background: Currently, a new generation of synthetic pulmonary surfactants is being developed that may eventually replace animal-derived surfactants used in the treatment of respiratory distress syndrome. Enlightened by this, we prepared a synthetic peptide-containing surfactant (Synsurf) consisting of phospholipids and poly-l-lysine electrostatically bonded to poly-l-glutamic acid. Our objective in this study was to investigate if bronchoalveolar lavage (BAL)-induced acute lung injury and surfactant deficiency with accompanying hypoxemia and increased alveolar and physiological dead space is restored to its prelavage condition by surfactant replacement with Synsurf, a generic prepared Exosurf, and a generic Exosurf containing Ca²⁺. Methods: Twelve adult New Zealand white rabbits receiving conventional mechanical ventilation underwent repeated BAL to create acute lung injury and surfactant-deficient lung disease. Synthetic surfactants were then administered and their effects assessed at specified time points over 5 hours. The variables assessed before and after lavage and surfactant treatment included alveolar and physiological dead space, dead space/tidal volume ratio, arterial end-tidal carbon dioxide tension (PCO₂) difference (mainstream capnography), arterial blood gas analysis, calculated shunt, and oxygen ratios. Results: BAL led to acute lung injury characterized by an increasing arterial PCO₂ and a simultaneous increase of alveolar and physiological dead space/tidal volume ratio with no intergroup differences. Arterial end-tidal PCO₂ and dead space/tidal volume ratio correlated in the Synsurf, generic Exosurf and generic Exosurf containing Ca²⁺ groups. A significant and sustained improvement in systemic oxygenation occurred from time point 180 minutes onward in animals treated with Synsurf compared to the other two groups (P ˂ 0.001). A statistically significant decrease in pulmonary shunt (P ˂ 0.001) was found for the Synsurf-treated group of animals, as well as radiographic improvement in three out of four animals in that group. Conclusion: In general, surfactant-replacement therapy in the animals did not fully restore the lung to its prelavage condition. However, our data show that the formulated surfactant Synsurf improves oxygenation by lowering pulmonary shunt.