title: Hemorrhagic shock-induced endothelial cell activation in a spontaneous breathing and a mechanical ventilation hemorrhagic shock model is induced by a proinflammatory response and not by hypoxia.
abstract: BACKGROUND
  The interaction between neutrophils and activated endothelium is essential for the development of multiple organ dysfunction in patients with hemorrhagic shock (HS). Mechanical ventilation frequently is used in patients with HS. The authors sought to investigate the consequences of mechanical ventilation of mice subjected to HS on microvascular endothelial activation in the lung and kidney.
  
  
  METHODS
  Anesthetized wild type C57BL/6 male mice were subjected to controlled hemorrhage; subgroups of mice were mechanically ventilated during the HS insult. To study the effect of acute hypoxia on the mice, the animals were housed in hypoxic cages. Gene expression levels was assessed by quantitative real-time polymerase chain reaction. Protein expression was assessed by immunohistochemistry and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Ninety minutes after the shock induction, a vascular bed-specific, heterogeneous proinflammatory endothelial activation represented by E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 expression was seen in kidney and lung. No differences in adhesion molecules between the spontaneously breathing and mechanically ventilated mice were found. Concentrations of the proinflammatory cytokines chemokine (C-X-C motif) ligand 1 (11.0-fold) and interleukin-6 (21.7-fold) were increased after 90 min of HS. Two hours of 6% oxygen did not induce the expression of E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 in the kidneys and the lung.
  
  
  CONCLUSIONS
  Hemorrhagic shock leads to an early and reversible proinflammatory endothelial activation in kidney and lung. HS-induced endothelial activation is not changed by mechanical ventilation during the shock phase. Hypoxia alone does not lead to endothelial activation. The observed proinflammatory endothelial activation is mostly ischemia- or reperfusion-dependent and not related to hypoxia.
authors.affiliation: Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.van.meurs@icv.umcg.nl
authors.forename: Matijs
authors.initials: M
authors.lastname: van Meurs
authors.forename: Francis M
authors.initials: FM
authors.lastname: Wulfert
authors.forename: Rianne M
authors.initials: RM
authors.lastname: Jongman
authors.forename: Martin
authors.initials: M
authors.lastname: Schipper
authors.forename: Martin C
authors.initials: MC
authors.lastname: Houwertjes
authors.forename: Michiel
authors.initials: M
authors.lastname: Vaneker
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Teppema
authors.forename: Leon P H J
authors.initials: LP
authors.lastname: Aarts
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.forename: Grietje
authors.initials: G
authors.lastname: Molema
mesh_terms: D000818:Animals; D054428:Chemokine CX3CL1 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D000860:Hypoxia / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012121:Respiration, Artificial / Q000009:adverse effects*; D015656:Respiratory Mechanics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010100:Oxygen