New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs

• Published in: PloS one 2012-10, Vol.7 (10), p.e47631
• Main Authors: Seehase, Matthias, Collins, Jennifer J P, Kuypers, Elke, Jellema, Reint K, Ophelders, Daan R M G, Ospina, Olga L, Perez-Gil, J, Bianco, Federico, Garzia, Raffaella, Razzetti, Roberta, Kramer, Boris W
• Format: Article
• Language: English
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - administration & dosage; 1,2-Dipalmitoylphosphatidylcholine - pharmacology; Albumin; Alveoli; Analogs; Animals; Babies; Biological Products - administration & dosage; Biological Products - pharmacology; Biology; Blood proteins; Bronchus; Compression; Deactivation; Female; Gestational age; Histology; In vivo methods and tests; Inactivation; Lung - drug effects; Lung - pathology; Lung - physiopathology; Lungs; Male; Mechanical ventilation; Medicine; Neonates; Newborn babies; Oxygenation; pH effects; Phosphatidylglycerols - administration & dosage; Phosphatidylglycerols - pharmacology; Phospholipids - administration & dosage; Phospholipids - pharmacology; Physiological aspects; Pregnancy; Premature Birth - drug therapy; Premature Birth - mortality; Premature infants; Prevention; Protein B; Pulmonary Surfactant-Associated Protein B - pharmacology; Pulmonary Surfactant-Associated Protein C - pharmacology; Pulmonary Surfactant-Associated Proteins - administration & dosage; Pulmonary Surfactant-Associated Proteins - pharmacology; Pulmonary Surfactants - administration & dosage; Pulmonary Surfactants - pharmacology; Rabbits; Respiratory distress syndrome; Respiratory therapy; Risk factors; Rodents; Serum albumin; Sheep; Surface active agents; Survival; Ventilation; Ventilators
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047631

Respiratory distress syndrome in preterm babies is caused by a pulmonary surfactant deficiency, but also by its inactivation due to various conditions, including plasma protein leakage. Surfactant replacement therapy is well established, but clinical observations and in vitro experiments suggested that its efficacy may be impaired by inactivation. A new synthetic surfactant (CHF 5633), containing synthetic surfactant protein B and C analogs, has shown comparable effects on oxygenation in ventilated preterm rabbits versus Poractant alfa, but superior resistance against inactivation in vitro. We hypothesized that CHF 5633 is also resistant to inactivation by serum albumin in vivo. Nineteen preterm lambs of 127 days gestational age (term = 150 days) received CHF 5633 or Poractant alfa and were ventilated for 48 hours. Ninety minutes after birth, the animals received albumin with CHF 5633 or Poractant alfa. Animals received additional surfactant if P(a)O(2) dropped below 100 mmHg. A pressure volume curve was done post mortem and markers of pulmonary inflammation, surfactant content and biophysiology, and lung histology were assessed. CHF 5633 treatment resulted in improved arterial pH, oxygenation and ventilation efficiency index. The survival rate was significantly higher after CHF 5633 treatment (5/7) than after Poractant alfa (1/8) after 48 hours of ventilation. Biophysical examination of the surfactant recovered from bronchoalveolar lavages revealed that films formed by CHF 5633-treated animals reached low surface tensions in a wider range of compression rates than films from Poractant alfa-treated animals. For the first time a synthetic surfactant containing both surfactant protein B and C analogs showed significant benefit over animal derived surfactant in an in vivo model of surfactant inactivation in premature lambs.