title: Ventilator-induced endothelial activation and inflammation in the lung and distal organs.
abstract: BACKGROUND
  Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.
  
  
  METHODS
  Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH2O positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC).
  
  
  RESULTS
  Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs.
  
  
  CONCLUSIONS
  Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.
authors.affiliation: Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, 3584 EA, The Netherlands. m.a.hegeman@umcutrecht.nl
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hegeman
authors.forename: Marije P
authors.initials: MP
authors.lastname: Hennus
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Patricia Ac
authors.initials: PA
authors.lastname: Specht
authors.forename: Burkhard
authors.initials: B
authors.lastname: Lachmann
authors.forename: Nicolaas Jg
authors.initials: NJ
authors.lastname: Jansen
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: van Vught
authors.forename: Pieter M
authors.initials: PM
authors.lastname: Cobelens
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000503:physiopathology*; D055370:Lung Injury / Q000209:etiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010366:Peak Expiratory Flow Rate; D011650:Pulmonary Alveoli / Q000502:physiology; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D014140:Tracheotomy