title: Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.
abstract: BACKGROUND
  Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth.
  
  
  OBJECTIVE
  To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.
  
  
  METHODS
  The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.
  
  
  RESULTS
  Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.
  
  
  CONCLUSIONS
  Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.
authors.affiliation: Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University, Saint Louis, MO, 63104, United States of America.
authors.forename: Rebecca Y
authors.initials: RY
authors.lastname: Petersen
authors.affiliation: Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University, Saint Louis, MO, 63104, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Royse
authors.affiliation: School of Women and Infants' Health, University of Western Australia, Perth, WA, 6009, Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.affiliation: School of Women and Infants' Health, University of Western Australia, Perth, WA, 6009, Australia.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miura
authors.affiliation: School of Women and Infants' Health, University of Western Australia, Perth, WA, 6009, Australia.
authors.forename: Andres
authors.initials: A
authors.lastname: Noe
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 45229, United States of America.|School of Women and Infants' Health, University of Western Australia, Perth, WA, 6009, Australia.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Division of Neonatology, Cardinal Glennon Children's Hospital, Saint Louis University, Saint Louis, MO, 63104, United States of America.
authors.forename: Noah H
authors.initials: NH
authors.lastname: Hillman
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology*; D000818:Animals; D001238:Asphyxia Neonatorum / Q000628:therapy*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D008168:Lung / Q000276:immunology / Q000473:pathology*; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D012756:Sheep
chemical_list: D015415:Biomarkers; D016207:Cytokines