Linking lung function and inflammatory responses in ventilator-induced lung injury

Vincenzo Cannizzaro, Z. Hantos, Peter D. Sly, Graeme R. Zosky

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume300
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Ventilator-Induced Lung Injury
Lung
Positive-Pressure Respiration
Tidal Volume
Mechanics
Interleukin-1
Ventilation
Interleukin-6
129 Strain Mouse
Inflammation
Dimercaprol
Plethysmography
Pulmonary Atelectasis
Interleukin-3
Pulmonary Edema
Principal Component Analysis
Artificial Respiration
Statistical Factor Analysis
Pneumonia
Proteins

Keywords

  • Forced oscillation technique
  • Lung volume
  • Mouse
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Linking lung function and inflammatory responses in ventilator-induced lung injury. / Cannizzaro, Vincenzo; Hantos, Z.; Sly, Peter D.; Zosky, Graeme R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 300, No. 1, 01.2011.

Research output: Contribution to journalArticle

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