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Published ahead of print on January 7, 2005, doi:10.1164/rccm.200408-1053OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 743-752, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200408-1053OC

Original Article

Lung Development and Susceptibility to Ventilator-induced Lung Injury

Alik Kornecki, Shinya Tsuchida, Hari Kumar Ondiveeran, Doreen Engelberts, Helena Frndova, A. Keith Tanswell, Martin Post, Colin McKerlie, Jaques Belik, Alison Fox-Robichaud and Brian P. Kavanagh

Lung Biology Program, Departments of Critical Care Medicine and Pediatrics, Hospital for Sick Children; Departments of Anesthesia, Pediatrics, Physiology, and the Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto; Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton; Department of Pediatrics (Critical Care Unit, Children's Hospital of Western Ontario), University of Western Ontario, London, Ontario, Canada

Correspondence and requests for reprints should be addressed to Brian P. Kavanagh, M.D., Department of Critical Care Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. E-mail: brian.kavanagh{at}sickkids.ca

Rationale: Ventilator-induced lung injury has been predominantly studied in adults. Objectives: 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. Measurements: 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. Main 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. Conclusion: 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.

Key Words: infant • lung injury • mechanical ventilation • pediatric • ventilator-induced lung injury




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