title: Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits.
abstract: BACKGROUND
  The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years.
  
  
  OBJECTIVE
  To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome.
  
  
  METHODS
  Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated.
  
  
  RESULTS
  Treatment with Curosurf or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (VT) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small VT, but after addition of both analogues VT was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on VT and LGV as Curosurf.
  
  
  CONCLUSIONS
  Phospholipid composition is important for VT while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding VT and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.
authors.affiliation: Laboratory for Surfactant Research, Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calkovska
authors.forename: Bim
authors.initials: B
authors.lastname: Linderholm
authors.forename: Marie
authors.initials: M
authors.lastname: Haegerstrand-Björkman
authors.forename: Barbara
authors.initials: B
authors.lastname: Pioselli
authors.forename: Nicola
authors.initials: N
authors.lastname: Pelizzi
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Tore
authors.initials: T
authors.lastname: Curstedt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004355:Drug Stability; D010743:Phospholipids / Q000032:analysis*; D047928:Premature Birth / Q000188:drug therapy* / Q000378:metabolism / Q000662:veterinary; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D010743:Phospholipids; D011663:Pulmonary Surfactants