title: Mesenteric ischemia-reperfusion injury: clearly improved hemodynamics but only minor protection of the rat small intestine by (sub)therapeutic heparin sodium and enoxaparin doses.
abstract: BACKGROUND
  Tissue protection against ischemia (I)/reperfusion (R) injury by heparins can be due to their anticoagulant and/or non-anticoagulant properties. Here we studied the protective potential of the anticoagulant and the non-anticoagulant features of heparin sodium (HepSo) and enoxaparin (Enox) against mesenteric I/R injury in a rat model.
  
  
  METHODS
  Mesenteric I/R was induced in rats (n = 6 per group) by superior mesenteric artery occlusion (SMAO; 90 min) and reopening (120 min). Therapeutic/clinical and subtherapeutic/non-anticoagulant doses of HepSo (0.25 mg/kg bolus + 0.25 mg/kg × h; 0.05 mg/kg bolus + 0.1 mg/kg × h) or Enox (0.5 mg/kg bolus + 0.5 mg/kg × h; 0.05 mg/kg bolus + 0.1 mg/kg × h) were administered intravenously starting 30 min before SMAO to the end of reperfusion. Systemic/vital and intestinal microcirculatory parameters were measured during the whole experimental procedure, those of small intestine injury at the end.
  
  
  RESULTS
  During intestinal reperfusion, mean arterial blood pressure and heart rates were significantly increased by HepSo and, less effectively, by Enox, in a dose-dependent manner. Intestinal microcirculation was only affected by the therapeutic HepSo dose, which decreased the microvascular flow and S(O2) during reperfusion. The subtherapeutic Enox treatment, as opposed to any HepSo dose, most effectively diminished I/R-induced intestinal hemorrhages, myeloperoxidase activity (as a measure of neutrophil invasion), and histopathological changes.
  
  
  CONCLUSIONS
  Therapeutic but, to a lesser extent, also the subtherapeutic doses of both HepSo and Enox clearly improve hemodynamics during mesenteric reperfusion, while intestinal protection is exclusively provided by Enox, especially at its subtherapeutic dose. Alterations in intestinal microcirculation are not responsible for these effects. Thus, non-anticoagulant Enox doses and, preferably, heparin(oid)s unable to affect coagulation, could diminish clinical risks of I/R-induced gastrointestinal complications.
authors.affiliation: Institut für Physiologische Chemie, Universitätsklinikum, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Walensi
authors.forename: Herbert
authors.initials: H
authors.lastname: de Groot
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Matthias
authors.initials: M
authors.lastname: Hartmann
authors.forename: Frank
authors.initials: F
authors.lastname: Petrat
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006493:Heparin; D009195:Peroxidase