Published ahead of print on May 4, 2006, doi:10.1164/rccm.200506-1006OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200506-1006OC
Atelectasis Causes Alveolar Injury in Nonatelectatic Lung RegionsLung Biology Program, and Departments of Critical Care Medicine and Radiology, Hospital for Sick Children; Departments of Anesthesia, Laboratory Medicine, and Physiology, and the Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; and School of Medicine and Medical Sciences, Conway Institute, University College Dublin, Dublin, Ireland 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, M5G 1X8 Canada. E-mail: brian.kavanagh{at}sickkids.ca Rationale: Many authors have suggested that the mechanism by which atelectasis contributes to injury is through the repetitive opening and closing of distal airways in lung regions that are atelectatic. However, neither the topographic nor mechanistic relationships between atelectasis and distribution of lung injury are known. Objectives: To investigate how atelectasis contributes to ventilator-induced lung injury. Methods: Surfactant depletion was performed in anesthetized rats that were then allocated to noninjurious or injurious ventilation for 90 min. Measurements: Lung injury was quantified by gas exchange, compliance, histology, wet-to-dry weight, and cytokine expression, and its distribution by histology, stereology, cytokine mRNA expression, in situ hybridization, and immunohistochemistry. Functional residual capacity, percent atelectasis, and injury-induced lung water accumulation were measured using gravimetric and volumetric techniques. Main Results: Atelectasis occurred in the dependent lung regions. Injurious ventilation was associated with alveolar and distal airway injury, while noninjurious ventilation was not. With injurious ventilation, alveolar injury (i.e., histology, myeloperoxidase protein expression, quantification, and localization of cytokine mRNA expression) was maximal in nondependent regions, whereas distal airway injury was equivalent in atelectatic and nonatelectatic regions. Conclusions: These data support the notion that lung injury associated with atelectasis involves trauma to the distal airways. We provide topographic and biochemical evidence that such distal airway injury is not localized solely to atelectatic areas, but is instead generalized in both atelectatic and nonatelectatic lung regions. In contrast, alveolar injury associated with atelectasis does not occur in those areas that are atelectatic but occurs instead in remote nonatelectatic alveoli.
Key Words: atelectasis • distribution • ventilator-induced lung injury This article has been cited by other articles:
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