Published ahead of print on January 7, 2005, doi:10.1164/rccm.200408-1053OC
Am. J. Respir. Crit. Care Med., Volume 171, Number 7, April 2005, 743-752
A more recent version of this article appeared on April 1, 2005
Submitted on August 15, 2004
Accepted on January 1, 2005
Lung Development and Susceptibility to Ventilator-Induced Lung Injury
Alik Kornecki1, Shinya Tsuchida1, Hari Kumar Ondiveeran2, Doreen Engelberts3, Helena Frndova3, A. Keith Tanswell4, Martin Post5, Colin McKerlie5, Jaques Belik4, Alison Fox-Robichaud2, and Brian P Kavanagh6*
1 Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada,
2 Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada,
3 Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada,
4 Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada,
5 Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada,
6 Lung Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: brian.kavanagh{at}sickkids.ca.
Rationale: Ventilator-induced lung injury has been predominantly studied in the adult.
Objectives: To explore the effects of age and lung development on susceptibility to such injury.
Methods: Ex vivo isolated non-perfused rat lungs (infant, juvenile, and adult) were mechanical ventilated where tidal volume was based on milliliters per kilogram body weight, or as a percentage of the measured total lung capacity. In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited tidal volumes. Allocation to ventilation strategy was randomized.
Measurements: Ex vivo injury was assessed by pressure-volume analysis, reduction in total lung capacity, and histology, and in vivo injury by lung compliance, cytokine production and wet-to-dry weight ratio.
Main Results: Ex vivo ventilation (tidal volume 30 mL/kg) resulted in a significant reduction (36.0±10.1%, P<0.05) in total lung capacity in adult, but not in infant lungs. Ex vivo ventilation (tidal volume 50% total lung capacity) resulted in a significant reduction in total lung capacity 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. Following high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, TNF- ). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult vs. 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.
Key words: Lung injury, infant, mechanical ventilation, ventilator-induced lung injury, pediatric
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