Volutrauma, but not Atelectrauma, Induces Systemic Cytokine Production by Lung-Marginated Monocytes
File(s)
Accepted version
Author(s)
Wakabayashi, K
Wilson, MR
Tatham, KC
O'Dea, KP
Takata, M
Type
Journal Article
Abstract
Objectives:
Ventilator-induced lung injury has substantive impact on mortality of patients with acute respiratory distress syndrome. Although low tidal volume ventilation has been shown to reduce mortality, clinical benefits of open-lung strategy are controversial. In this study, we investigated the impact of two distinct forms of ventilator-induced lung injury, i.e., volutrauma and atelectrauma, on the progression of lung injury and inflammation, in particular alveolar and systemic cytokine production.
Design:
Ex vivo study.
Setting:
University research laboratory.
Subjects:
C57BL/6 mice.
Interventions:
Isolated, buffer-perfused lungs were allocated to one of three ventilatory protocols for 3 hours: control group received low tidal volume (7 mL/kg) with positive end-expiratory pressure (5 cm H2O) and regular sustained inflation; high-stretch group received high tidal volume (30–32 mL/kg) with positive end-expiratory pressure (3 cm H2O) and sustained inflation; and atelectasis group received the same tidal volume as control but neither positive end-expiratory pressure nor sustained inflation.
Measurements and Main Results:
Both injurious ventilatory protocols developed comparable levels of physiological injury and pulmonary edema, measured by respiratory system mechanics and lavage fluid protein. High-stretch induced marked increases in proinflammatory cytokines in perfusate and lung lavage fluid, compared to control. In contrast, atelectasis had no effect on perfusate cytokines compared to control but did induce some up-regulation of lavage cytokines. Depletion of monocytes marginated within the lung microvasculature, achieved by pretreating mice with IV liposome-encapsulated clodronate, significantly attenuated perfusate cytokine levels, especially tumor necrosis factor, in the high-stretch, but not atelectasis group.
Conclusions:
Volutrauma (high-stretch), but not atelectrauma (atelectasis), directly activates monocytes within the pulmonary vasculature, leading to cytokine release into systemic circulation. We postulate this as a potential explanation why open-lung strategy has limited mortality benefits in ventilated critically ill patients.
Ventilator-induced lung injury has substantive impact on mortality of patients with acute respiratory distress syndrome. Although low tidal volume ventilation has been shown to reduce mortality, clinical benefits of open-lung strategy are controversial. In this study, we investigated the impact of two distinct forms of ventilator-induced lung injury, i.e., volutrauma and atelectrauma, on the progression of lung injury and inflammation, in particular alveolar and systemic cytokine production.
Design:
Ex vivo study.
Setting:
University research laboratory.
Subjects:
C57BL/6 mice.
Interventions:
Isolated, buffer-perfused lungs were allocated to one of three ventilatory protocols for 3 hours: control group received low tidal volume (7 mL/kg) with positive end-expiratory pressure (5 cm H2O) and regular sustained inflation; high-stretch group received high tidal volume (30–32 mL/kg) with positive end-expiratory pressure (3 cm H2O) and sustained inflation; and atelectasis group received the same tidal volume as control but neither positive end-expiratory pressure nor sustained inflation.
Measurements and Main Results:
Both injurious ventilatory protocols developed comparable levels of physiological injury and pulmonary edema, measured by respiratory system mechanics and lavage fluid protein. High-stretch induced marked increases in proinflammatory cytokines in perfusate and lung lavage fluid, compared to control. In contrast, atelectasis had no effect on perfusate cytokines compared to control but did induce some up-regulation of lavage cytokines. Depletion of monocytes marginated within the lung microvasculature, achieved by pretreating mice with IV liposome-encapsulated clodronate, significantly attenuated perfusate cytokine levels, especially tumor necrosis factor, in the high-stretch, but not atelectasis group.
Conclusions:
Volutrauma (high-stretch), but not atelectrauma (atelectasis), directly activates monocytes within the pulmonary vasculature, leading to cytokine release into systemic circulation. We postulate this as a potential explanation why open-lung strategy has limited mortality benefits in ventilated critically ill patients.
Date Issued
2014-01-01
Date Acceptance
2014-01-01
Citation
Critical Care Medicine, 2014, 42 (1), pp.e49-e57
ISSN
0090-3493
Publisher
Lippincott, Williams & Wilkins
Start Page
e49
End Page
e57
Journal / Book Title
Critical Care Medicine
Volume
42
Issue
1
Copyright Statement
© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
Identifier
https://journals.lww.com/ccmjournal/Abstract/2014/01000/Volutrauma,_but_not_Atelectrauma,_Induces_Systemic.51.aspx
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
General & Internal Medicine
acute respiratory distress syndrome
atelectasis
biotrauma
mechanical ventilation
monocytes
stretch
RESPIRATORY-DISTRESS-SYNDROME
END-EXPIRATORY PRESSURE
TUMOR-NECROSIS-FACTOR
HIGH TIDAL VOLUME
VIVO MOUSE MODEL
MECHANICAL VENTILATION
PULMONARY-EDEMA
INDUCED INJURY
ALVEOLAR
ATELECTASIS
Animals
Cytokines
Edema
Flow Cytometry
Lung
Male
Mice
Mice, Inbred C57BL
Monocytes
Positive-Pressure Respiration
Tidal Volume
Ventilator-Induced Lung Injury
Lung
Monocytes
Animals
Mice, Inbred C57BL
Mice
Edema
Cytokines
Tidal Volume
Positive-Pressure Respiration
Flow Cytometry
Male
Ventilator-Induced Lung Injury
Emergency & Critical Care Medicine
1103 Clinical Sciences
1110 Nursing
1117 Public Health and Health Services
Publication Status
Published