title: Atherosclerosis aggravates ischemia/reperfusion injury in the gut and remote damage in the liver and the lung.
abstract: OBJECTIVE
  We investigated whether mesenteric ischemia/reperfusion (I/R)-associated gut injury and remote liver and lung damage are affected by prevalent atherosclerosis.
  
  
  METHODS
  Mesenteric ischemia was induced in atherosclerotic ApoE-deficient (ApoE(-/-)) and control C57BL/6 mice by clamping the superior mesenteric artery for 30 min. Mesenteric microcirculatory dysfunction and leukocytic inflammation were studied in the terminal ileum by intravital fluorescence microscopy (IVM). Histological analyses included quantitative assessment of parenchymal injury in the terminal ileum, liver and lung.
  
  
  RESULTS
  In the gut, IVM of the terminal ileum revealed aggravated postischemic microcirculatory dysfunction and absence of reactive hyperemia-induced vasodilation in atherosclerotic mice compared to controls. In addition, leukocyte-endothelial cell adhesive interactions, i.e. rolling and firm adhesion, were significantly increased in atherosclerotic animals. This was associated with enhanced mucosal tissue damage in ApoE(-/-) mice. Moreover, mesenteric I/R-provoked remote parenchymal injury in the liver was found to be significantly aggravated in atherosclerotic mice. This was accompanied by enhanced neutrophilic lung inflammation in ApoE(-/-) mice.
  
  
  CONCLUSIONS
  Prevalent generalized atherosclerosis not only aggravates splanchnic microcirculatory dysfunction and leukocytic inflammation in response to mesenteric I/R, but also exacerbates mucosal tissue damage and remote injury in the liver and the lung.
authors.affiliation: Clinic of Cardiac Surgery, Ludwig-Maximilians-University of Munich-Grosshadern, Marchioninistr.15, 81377, Munich, Germany. reneschramm@live.de
authors.forename: René
authors.initials: R
authors.lastname: Schramm
authors.forename: Frank
authors.initials: F
authors.lastname: Appel
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinacher
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schäfers
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bierbach
authors.forename: Jan
authors.initials: J
authors.lastname: Slotta
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D007082:Ileum / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000473:pathology; D036904:Leukocyte Rolling; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D009130:Muscle, Smooth / Q000098:blood supply / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001057:Apolipoproteins E