Objective Surfaxin® contains KL4 (sinapultide), a novel synthetic peptide that functionally mimics SP-B, a protein with anti-inflammatory properties insufficient in animal-derived surfactant replacement therapy (SRT). Here, we test the hypothesis that Surfaxin® confers greater protection against ventilator/hyperoxia-induced lung inflammation than animal-derived SRT in preterm lambs with RDS.

Design and Methods Preterm lambs (n = 24; 126.8±0.2 SE days gestation) were delivered ventilated (FIO₂ = 1), randomized to SRT with Surfaxin® (175 mg/kg), Curosurf® (175 mg/kg), Survanta® (100 mg/kg), or no SRT (control) and studied for 4 hrs. Cardiopulmonary parameters were monitored. Lung tissue IL-8, IL-6, myeloperoxidase (MPO) and histomorphometry were measured.

Results By 4 hrs, PaO₂ and compliance in all SRT groups were greater (p<0.05) than control. Ventilation efficiency index was greater (p<0.05) with Surfaxin® than Curosurf® or Survanta®. Surfaxin® treated animals demonstrated lower lung IL-8 (p<0.05 vs all other groups), IL-6 (p<0.05 vs control; p<0.10 vs other SRT groups) and MPO (p<0.001 vs control; p<0.10 vs other SRT groups) and greater lung expansion index (p<0.001 vs control; p<0.10 vs vs other SRT groups).

Conclusions Surfaxin attenuated lung inflammation and preserved lung structure in preterm lambs with RDS more than either no SRT or SRT with animal-derived surfactant. To the degree that inflammation may lead to functional compromise and existing SRT formulations lack sufficient anti-inflammatory proteins, these data suggest that early intervention with Surfaxin may mitigate progression of RDS to bronchopulmonary dysplasia.

Supported by: Discovery Laboratories, Inc.