title: Lung development and susceptibility to ventilator-induced lung injury.
abstract: BACKGROUND
  Ventilator-induced lung injury has been predominantly studied in adults.
  
  
  OBJECTIVE
  To explore the effects of age and lung development on susceptibility to such injury.
  
  
  METHODS
  Ex vivo isolated nonperfused rat lungs (infant, juvenile, and adult) were mechanically ventilated where VT was based on milliliters per kilogram of body weight or as a percentage of the measured total lung capacity (TLC). In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited VTs. Allocation to ventilation strategy was randomized.
  
  
  METHODS
  Ex vivo injury was assessed by pressure-volume analysis, reduction in TLC, and histology, and in vivo injury by lung compliance, cytokine production, and wet- to dry-weight ratio.
  
  
  RESULTS
  Ex vivo ventilation (VT 30 ml.kg(-1)) resulted in a significant reduction (36.0 +/- 10.1%, p < 0.05) in TLC in adult but not in infant lungs. Ex vivo ventilation (VT 50% TLC) resulted in a significant reduction in TLC in both adult (27.8 +/- 2.8%) and infant (10.6 +/- 7.0%) lungs, but more so in the adult lungs (p < 0.05); these changes were paralleled by histology and pressure-volume characteristics. After high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, tumor necrosis factor alpha). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult versus infant lungs.
  
  
  CONCLUSIONS
  These data provide ex vivo and in vivo evidence that comparable ventilator settings are significantly more injurious in the adult than infant rat lung, probably reflecting differences in intrinsic susceptibility or inflation pattern.
authors.affiliation: Lung Biology Program, Department of Critical Care Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8.
authors.forename: Alik
authors.initials: A
authors.lastname: Kornecki
authors.forename: Shinya
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Hari Kumar
authors.initials: HK
authors.lastname: Ondiveeran
authors.forename: Doreen
authors.initials: D
authors.lastname: Engelberts
authors.forename: Helena
authors.initials: H
authors.lastname: Frndova
authors.forename: A Keith
authors.initials: AK
authors.lastname: Tanswell
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
authors.forename: Jaques
authors.initials: J
authors.lastname: Belik
authors.forename: Alison
authors.initials: A
authors.lastname: Fox-Robichaud
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kavanagh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004195:Disease Models, Animal; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D011336:Probability; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000032:analysis / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014109:Total Lung Capacity
chemical_list: D011663:Pulmonary Surfactants