title: New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Seehase
authors.forename: Jennifer J P
authors.initials: JJ
authors.lastname: Collins
authors.forename: Elke
authors.initials: E
authors.lastname: Kuypers
authors.forename: Reint K
authors.initials: RK
authors.lastname: Jellema
authors.forename: Daan R M G
authors.initials: DR
authors.lastname: Ophelders
authors.forename: Olga L
authors.initials: OL
authors.lastname: Ospina
authors.forename: J
authors.initials: J
authors.lastname: Perez-Gil
authors.forename: Federico
authors.initials: F
authors.lastname: Bianco
authors.forename: Raffaella
authors.initials: R
authors.lastname: Garzia
authors.forename: Roberta
authors.initials: R
authors.lastname: Razzetti
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000494:pharmacology*; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy / Q000401:mortality; D037701:Pulmonary Surfactant-Associated Protein B / Q000494:pharmacology; D037721:Pulmonary Surfactant-Associated Protein C / Q000494:pharmacology; D037661:Pulmonary Surfactant-Associated Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep
chemical_list: D001688:Biological Products; D010715:Phosphatidylglycerols; D010743:Phospholipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C068291:poractant alfa