title: The effect of tidal volume on systemic inflammation in Acid-induced lung injury.
abstract: BACKGROUND
  Overwhelming systemic inflammation has been implicated in the progression of acute lung injury (ALI) leading to multiple organ failure (MOF) and death. Previous studies suggest that mechanical ventilation (MV) may be a key mediator of MOF through an upregulation of the systemic inflammatory response.
  
  
  OBJECTIVE
  It was the aim of this study to investigate mechanisms whereby mechanical stress induced by different tidal volumes may contribute to the development of systemic inflammation and maladaptive peripheral organ responses in the setting of ALI.
  
  
  METHODS
  An acid aspiration model of ALI was employed in 129X1/SVJ mice through an intratracheal administration of hydrochloric acid followed by MV employing either a low (5 ml/kg) or high (12.5 ml/kg) tidal volume ventilation for 120 min. The isolated perfused mouse lung setup was used to assess the specific contribution of the lung to systemic inflammation during MV. Furthermore, lung perfusate collected over the course of MV was used to assess the effects of lung-derived mediators on activation (expression of a proadhesive phenotype) of liver endothelial cells.
  
  
  RESULTS
  High tidal volume MV of acid-injured lungs resulted in greater physiologic and histological indices of lung injury compared to control groups. Additionally, there was an immediate and significant release of multiple inflammatory mediators from the lung into the systemic circulation which resulted in greater levels of mRNA adhesion molecule expression in liver endothelial cells in vitro.
  
  
  CONCLUSIONS
  This study suggests that MV, specifically tidal volume strategy, influences the development of MOF through an upregulation of lung-derived systemic inflammation resulting in maladaptive cellular changes in peripheral organs.
authors.affiliation: Lawson Health Research Institute, London, Ont., Canada.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Walker
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Yao
authors.forename: Eric K
authors.initials: EK
authors.lastname: Patterson
authors.forename: Mariamma G
authors.initials: MG
authors.lastname: Joseph
authors.forename: Gediminas
authors.initials: G
authors.lastname: Cepinskas
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.forename: Cory M
authors.initials: CM
authors.lastname: Yamashita
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D042783:Endothelial Cells / Q000378:metabolism; D006851:Hydrochloric Acid; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009102:Multiple Organ Failure / Q000209:etiology* / Q000503:physiopathology; D012121:Respiration, Artificial / Q000379:methods; D013990:Tidal Volume
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D006851:Hydrochloric Acid