title: Cerebral and lung effects of a new generation synthetic surfactant with SP-B and SP-C analogs in preterm lambs.
abstract: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS.
  
  
  
  Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed.
  
  
  
  After delivery, lambs developed severe RDS (FIO2:1, pH < 7.15, PaCO2> 70 mmHg, PaO2< 40 mmHg, Cdyn< 0.1 mL/cmH2O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, PaCO2, carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls.
  
  
  
  Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment.
authors.affiliation: Animal Research Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rey-Santano
authors.affiliation: Animal Research Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Mielgo
authors.affiliation: Animal Research Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Murgia
authors.affiliation: Medical Devices Group, University of Basque Country, Portugalete, Bizkaia, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Gomez-Solaetxe
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salomone
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Bianco
authors.affiliation: Chiesi Farmaceutici, R&D Department, Parma, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pelizzi
authors.affiliation: Neonatal Intensive Care Unit, Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Loureiro
authors.affiliation: Neonatal Intensive Care Unit, Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: López de Heredia Y Goya
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001688:Biological Products / Q000627:therapeutic use; D001784:Blood Gas Analysis; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006439:Hemodynamics; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D010713:Phosphatidylcholines / Q000627:therapeutic use*; D010743:Phospholipids / Q000627:therapeutic use; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D037701:Pulmonary Surfactant-Associated Protein B / Q000627:therapeutic use*; D037721:Pulmonary Surfactant-Associated Protein C / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012756:Sheep; D013552:Swine
chemical_list: D001688:Biological Products; C000592408:CHF5633; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010743:Phospholipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; C068291:poractant alfa
keywords: brain; histology; neonate; respiratory distress syndrome; synthetic surfactant