Positive End-Expiratory Pressure Modifies Response to Recombinant and Natural Exogenous Surfactant in Ventilated Immature Newborn Rabbits

Abstract

Background and Objectives: Different types of surfactant preparations were shown not to exert uniform response in preterm infants suffering from respiratory distress syndrome (RDS). Therefore, the effects of a recombinant surfactant protein C (rSP-C) based preparation and a natural surfactant were compared applying different levels of positive end-expiratory pressure (PEEP) in experimental RDS. Methods: Preterm rabbits (n = 7–14 per group; 27 days gestation; term 30 days) were randomized for receiving either 100 mg/kg rSP-C or natural bovine surfactant and were compared with saline treated controls. Animals were ventilated for 30 min with either 0.3 or 0 kPa PEEP at standardized tidal volumes and lung mechanics were measured as well as lung histology and mRNA expression of surfactant associated proteins B and C by real-time PCR. Results: The PEEP level applied (0.3 vs. 0 kPa) largely influenced dynamic compliance after administration of rSP-C surfactant (4.45 vs. 2.58 ml/kg), whereas natural surfactant improved compliance regardless of the PEEP applied (4.86 vs. 4.24 ml/kg) compared to controls (2.41 vs. 1.55 ml/kg). Accordingly, administration of PEEP significantly increased alveolar count in all groups as well as SP-C mRNA expression, whereas SP-B expression and protein content both remained unchanged. Conclusion: Response to rSP-C surfactant depends on the PEEP level applied in our model of neonatal RDS. These findings should be considered for the conception of clinical trials regarding treatment strategies in neonatal RDS.