Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome

Neonatology. 2014;105(2):128-35. doi: 10.1159/000356065. Epub 2013 Dec 14.

Abstract

Background: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa.

Objective: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters.

Methods: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour.

Results: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses.

Conclusion: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Products / therapeutic use
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Humans
  • Infant, Newborn
  • Inflammation / drug therapy
  • Meconium Aspiration Syndrome / drug therapy*
  • Meconium Aspiration Syndrome / pathology
  • Peptide Fragments / administration & dosage*
  • Phosphatidylcholines / administration & dosage*
  • Phospholipids / therapeutic use
  • Pulmonary Surfactant-Associated Protein B / administration & dosage*
  • Pulmonary Surfactant-Associated Protein C / administration & dosage*
  • Pulmonary Surfactants / administration & dosage*
  • Random Allocation
  • Respiration / drug effects
  • Swine*

Substances

  • Biological Products
  • CHF5633
  • Peptide Fragments
  • Phosphatidylcholines
  • Phospholipids
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactants
  • poractant alfa