title: Mechanical ventilation injury and repair in extremely and very preterm lungs.
abstract: BACKGROUND
  Extremely preterm infants often receive mechanical ventilation (MV), which can contribute to bronchopulmonary dysplasia (BPD). However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood.
  
  
  OBJECTIVE
  To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs.
  
  
  METHODS
  Extremely preterm lambs (0.75 of term) were transiently exposed by hysterotomy and underwent 2 h of injurious MV. Lungs were collected 24 h and at 15 d after MV. Immunohistochemistry and morphometry were used to characterise injury and repair processes. qRT-PCR was performed on extremely and very preterm (0.85 of term) lungs 24 h after MV to assess molecular injury and repair responses.
  
  
  RESULTS
  24 h after MV at 0.75 of term, lung parenchyma and bronchioles were severely injured; tissue space and myofibroblast density were increased, collagen and elastin fibres were deformed and secondary crest density was reduced. Bronchioles contained debris and their epithelium was injured and thickened. 24 h after MV at 0.75 and 0.85 of term, mRNA expression of potential mediators of lung repair were significantly increased. By 15 days after MV, most lung injury had resolved without treatment.
  
  
  CONCLUSIONS
  Extremely immature lungs, particularly bronchioles, are severely injured by 2 h of MV. In the absence of continued ventilation these injured lungs are capable of repair. At 24 h after MV, genes associated with injurious MV are unaltered, while potential repair genes are activated in both extremely and very preterm lungs.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. Nadine.brew@monash.edu
authors.forename: Nadine
authors.initials: N
authors.lastname: Brew
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Hooper
authors.forename: Valerie
authors.initials: V
authors.lastname: Zahra
authors.forename: Megan
authors.initials: M
authors.lastname: Wallace
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight; D055745:Bronchioles / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005312:Fetal Blood / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009929:Organ Size; D047928:Premature Birth / Q000097:blood / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D055397:Ventilator-Induced Lung Injury / Q000097:blood / Q000196:embryology* / Q000235:genetics / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics
chemical_list: D004573:Electrolytes; D012333:RNA, Messenger; D003094:Collagen; D004247:DNA; D004549:Elastin