title: Cardiac ICAM-1 mediates leukocyte-dependent decreased ventricular contractility in endotoxemic mice.
abstract: OBJECTIVE
  Binding of ICAM-1 expressed on cardiomyocytes decreases cardiomyocyte contractility in vitro by altering the intracellular Ca2+ transient. We tested the hypothesis that signaling via ICAM-1 contributes to decreased left ventricular contractility in an in vivo model of systemic inflammation.
  
  
  METHODS
  C57B6 wild-type mice and ICAM-1 knock-out mice were treated with intraperitoneal lipopolysaccharide (LPS) then left ventricular contractility was measured 6 h later using a volume-conductance micromanometer catheter. We repeated this experiment in chimeric mice lacking ICAM-1 expression in bone marrow-derived cells (M-) and/or lacking ICAM-1 expression in the heart and other tissues (H-).
  
  
  RESULTS
  In C57B6 wild-type mice LPS injection significantly increased cardiac ICAM-1 expression and decreased in vivo measures of left ventricular contractility (end-systolic elastance, Ees decreased 58 +/- 4%, p < 0.05, [dP/dtmax]/EDV decreased 60 +/- 6%, p < 0.05). Cyclophosphamide pretreatment to decrease leukocyte count prevented the LPS-induced decrease in contractility. In ICAM-1 knock-out mice LPS did not decrease any measure of contractility. LPS did not decrease left ventricular contractility in M+/H- mice but decreased contractility in M+/H+ and M-/H+ mice to the same extent as in C57B6 wild-type mice implicating the importance of cardiac ICAM-1.
  
  
  CONCLUSIONS
  We conclude that signaling via cardiac ICAM-1 is necessary to mediate leukocyte-dependent decreases of left ventricular contractility in endotoxemic mice.
authors.affiliation: Critical Care Research Laboratories, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
authors.forename: Ehsan Y
authors.initials: EY
authors.lastname: Davani
authors.forename: John H
authors.initials: JH
authors.lastname: Boyd
authors.forename: Delbert R
authors.initials: DR
authors.lastname: Dorscheid
authors.forename: Yingjing
authors.initials: Y
authors.lastname: Wang
authors.forename: Anna
authors.initials: A
authors.lastname: Meredith
authors.forename: Edmond
authors.initials: E
authors.lastname: Chau
authors.forename: Gurpreet K
authors.initials: GK
authors.lastname: Singhera
authors.forename: Keith R
authors.initials: KR
authors.lastname: Walley
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry; D005340:Fibrinogen / Q000032:analysis; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000276:immunology* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D003520:Cyclophosphamide; D005340:Fibrinogen