title: Intercellular adhesion molecule-1 inhibition attenuates neurologic and hepatic damage after resuscitation in mice.
abstract: BACKGROUND
  Cardiac arrest and cardiopulmonary resuscitation may result in multiorgan damage after global hypoxia due to neutrophil recruitment. Patients display all signs of a systemic inflammatory response syndrome. Reducing neutrophil recruitment may thus preserve organ function.
  
  
  METHODS
  Mice were subjected to cardiac arrest and resuscitation. CD18/CD11b expression on circulating neutrophils was assessed by flow cytometry. Intercellular adhesion molecule-1 expression was analyzed by Western blot and immunofluorescence. Neutrophil recruitment was quantified by immunohistochemistry. Neurologic function was assessed by a balance test. For liver and kidney function, plasma alanine aminotransferase activity and creatinine concentrations were determined. To reduce neutrophil recruitment, mice received 100 microg anti-intercellular adhesion molecule-1 antibody intraperitoneally.
  
  
  RESULTS
  Resuscitation led to severe hypoxia, acidosis, and hypercarbia. Adhesion molecule expression and neutrophil recruitment were increased in the liver, kidney, and brain. Neurologic performance was impaired 24 h after cardiac arrest. Creatinine and alanine aminotransferase concentrations were significantly increased. Immunoneutralization of intercellular adhesion molecule-1 attenuated neutrophil influx in the liver along with alanine aminotransferase activity, whereas creatinine concentrations and neutrophil influx in the kidney remained unchanged. Neurologic function was improved in the treatment group.
  
  
  CONCLUSIONS
  Global hypoxia induces activation of the endothelium in the brain, liver, and kidney. The resulting damage to the brain and liver are due to infiltration of neutrophils, whereas kidney damage is not, because reduction of neutrophil recruitment after cardiopulmonary resuscitation improves recovery of neurologic and hepatic but not renal function. Inhibition of intercellular adhesion molecule-1 after global hypoxia may be beneficial in patients experiencing cardiac arrest and resuscitation.
authors.affiliation: Department of Anesthesiology and IZKF, University Hospital Münster, University of Münster, Vesaliusweg 2-4, 48149 Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Larmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmidt
authors.forename: Harald
authors.initials: H
authors.lastname: Gammelin
authors.forename: Hugo K
authors.initials: HK
authors.lastname: Van Aken
authors.forename: Tim
authors.initials: T
authors.lastname: Frenzel
authors.forename: Christian
authors.initials: C
authors.lastname: Lanckohr
authors.forename: Marleen
authors.initials: M
authors.lastname: Lox
authors.forename: Nadine
authors.initials: N
authors.lastname: Boese
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurk
authors.forename: Gregor
authors.initials: G
authors.lastname: Theilmeier
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D001784:Blood Gas Analysis; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000502:physiology; D005434:Flow Cytometry; D006324:Heart Arrest, Induced; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D007668:Kidney / Q000473:pathology; D008024:Ligands; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009475:Neurons, Afferent / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000502:physiology
chemical_list: D019138:Antibodies, Blocking; D008024:Ligands; D018799:Intercellular Adhesion Molecule-1