Article Text

SURFAXIN ATTENUATES INFLAMMATION AND PRESERVES LUNG STRUCTURE VERSUS ANIMAL-DERIVED SURFACTANT REPLACEMENT THERAPY (SRT) IN VENTILATED-HYPEROXIC RESPIRATORY DISTRESS SYNDROME (RDS) MODELS
  1. M R Wolfson1,
  2. D J Malone1,
  3. J Wu1,
  4. T Gregory2,
  5. J Mazela2,
  6. T H Shaffer1,3
  1. 1Physiology and Pediatrics, Temple University School of Medicine, Phila, PA, USA
  2. 2Discovery Laboratories, Inc., Warrington, PA, USA
  3. 3Nemours Lung Center, AIfred I. DuPont Hospital, Wilmington, DE, USA

Abstract

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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.