title: Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model.
abstract: Extracorporeal circulation induces ischemia/reperfusion injury in the small intestinal wall. One reason for this damage is a perfusion shift from the muscular toward the mucosal layer. This study investigated the effect of this perfusion shift on the small-intestinal apoptosis and proliferation.
  
  
  
  Twenty-eight pigs were randomly assigned to the following cohorts and underwent a thoracolaparotomy and a 1 hour main procedure: cohort I: control; cohort II: thoracic aortic cross-clamping (TAC) without perfusion; cohort III: TAC and distal aortic perfusion (DAP); cohort IV: TAC, DAP, and selective visceral perfusion. The main procedure was followed by 2 hours of reperfusion in all cohorts. Tissue samples were taken during the experiment, stained, and analyzed for apoptosis and proliferation (caspase-3, annexin-V, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling, and proliferating cell nuclear antigen). Six animals died unexpectedly during the experiment and were excluded from the analysis.
  
  
  
  Extensive tissue damage and necrosis was only found in cohort II after the main procedure. In the mucosa, the proliferation was increased in cohort III at the end of the experiment (P = .0157 cohort I vs II). In contrast, the annexin-V/proliferating cell nuclear antigen ratio was significantly higher in cohorts II and IV than in cohorts I and II at the end of the experiment (P = .0034). Furthermore, the caspase-3/annexin-V ratio was increased in all cohorts at the end of the experiment (P = .0015).
  
  
  
  Mucosal proliferation is the early repair mechanism of the limited small intestinal ischemia/reperfusion injury after DAP. Furthermore, the extensive surgical trauma shifted the mucosal apoptosis into an advanced state.
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany.
authors.forename: Paula Rosalie
authors.initials: PR
authors.lastname: Keschenau
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ribbe
authors.affiliation: Department of Medical Statistics, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tamm
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Surgery, Maastricht University Hospital, Maastricht, The Netherlands.
authors.forename: Sebastiaan J
authors.initials: SJ
authors.lastname: Hanssen
authors.affiliation: Institute for Laboratory Animal Science and Experimental Surgery, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Tolba
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany; European Vascular Center Aachen-Maastricht, Department of Surgery, Maastricht University Hospital, Maastricht, The Netherlands. Electronic address: m.jacobs@mumc.nl.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobs
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, Rheinisch-Westfälische Technische Hochschule University Hospital Aachen, Aachen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kalder
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012038:Regeneration; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D034421:Sus scrofa; D013997:Time Factors
chemical_list: D017304:Annexin A5; D018809:Proliferating Cell Nuclear Antigen; D053148:Caspase 3