Effects of a recombinant surfactant protein-C-based surfactant on lung function and the pulmonary surfactant system in a model of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome (MAS) remains a relevant cause of neonatal respiratory failure and is characterized by severe impairment of pulmonary gas exchange, surfactant inactivation, and pronounced inflammatory changes. Surfactant administration has been shown as an effective treatment strategy in MAS. The present study aimed at investigating the impact of a recombinant surfactant protein (SP)-C-based surfactant on pulmonary gas exchange and lung function in this model of neonatal lung injury. Furthermore, SP-B and -C were determined on the transcriptional and protein level. DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Twenty three newborn piglets (median age 6 days, weight 1900-2500 g). INTERVENTIONS: Piglets were intubated and mechanically ventilated and then received 20% sterile meconium (5 mL/kg) for induction of lung injury. After 30 mins, animals were randomized for control (n = 7, MAS controls), recombinant SP-C surfactant (n = 8), or natural surfactant (n = 8). Surfactant preparations were administered as an intratracheal bolus (75 mg/kg), and animals were ventilated for another 330 mins. Nonventilated newborn piglets at term (n = 28; median weight 1484 g, range 720-1990 g) served as a healthy reference group (healthy controls). MEASUREMENTS AND MAIN RESULTS: Lung function variables, arterial blood gas samples, and lung tissues were obtained. Expression of SP-B and -C messenger RNA was quantified in left lung lobe tissue using real-time polymerase chain reaction. Protein concentrations were determined by enzyme-linked immunosorbent assay. Scanning electron microscopy and transmission electron microscopy were performed in tissue samples of the right lung lobe. Compared with healthy controls, SP-B messenger RNA expression was significantly increased in MAS (p < .02), whereas SP-C messenger RNA expression was found to be significantly reduced (p < .001). SP concentrations, however, were not significantly different. Although a significant improvement of gas exchange and lung function was observed after surfactant administration in both groups, surfactant messenger RNA expression and protein concentrations were not significantly altered. Scanning and transmission electron microscopy showed severe pulmonary ultrastructural changes after meconium aspiration improving after surfactant treatment. CONCLUSIONS: Impairment of lung function in MAS, associated with marked changes in SP messenger RNA expression, can be sufficiently treated using recombinant SP-C-based or natural surfactant. Despite improved lung function and gas exchange as well as pulmonary ultrastructure after treatment, pulmonary SP messenger RNA expression and concentrations remained significantly affected, giving important insight into the time course following surfactant treatment in MAS.

Synthetic and natural surfactant differentially modulate inflammation after meconium aspiration.

OBJECTIVE: Meconium aspiration syndrome remains a relevant cause of neonatal respiratory failure and is associated with severe pulmonary changes including surfactant inactivation and pronounced inflammatory changes. The present study investigated the effect of two different surfactant preparations-recombinant surfactant protein C surfactant (rSP-C Surf) and natural bovine surfactant-on pulmonary gas exchange and inflammatory response. DESIGN AND SUBJECTS: Twenty-three newborn piglets were intubated, mechanically ventilated, received 5 ml/kg 20% sterile meconium for induction of lung injury, and were randomized thereafter for controls ( n=7), rSP-C Surf ( n=8), or natural surfactant ( n=8). Surfactants were given as an intratracheal bolus (75 mg/kg) and animals were further ventilated. MEASUREMENTS AND RESULTS: Lung function variables, arterial blood gas samples and lung tissues were obtained. Histological evaluation was performed in right lung tissue using an established score. Cytokine mRNA expression (left lung tissue) was quantified using TaqMan real-time PCR (DeltaDeltaCT method, normalized to controls). In addition to significant improvement in gas exchange and lung function, histological evaluation showed significantly lower sum scores in the rSP-C Surf group than in controls). Cytokine mRNA expression of IL-1beta in whole lung tissue was significantly lower after administration of rSP-C Surf than in natural surfactant and controls whereas IL-10 mRNA expression was significantly induced in both surfactant groups. CONCLUSIONS: Surfactant administration improved both gas exchange and pulmonary inflammatory cytokine transcription. Mechanisms underlying the differential inflammatory response in both surfactant preparations need to be further addressed.