title: Secondary burn progression decreased by erythropoietin.
abstract: OBJECTIVE
  To investigate whether systemic erythropoietin administration can prevent secondary burn progression in an experimental model and to elucidate the underlying mechanisms.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University-based laboratory research.
  
  
  METHODS
  Twenty-one male Wistar rats.
  
  
  METHODS
  The burn comb model creates four rectangular burned surfaces that are intercalated by three unburned zones (interspaces) prone to secondary necrosis. Twenty-one animals were randomized to three experimental groups: 1) Local cooling with water for 20 minutes (control, 17°C); 2) and 3) local cooling with water and intraperitoneal erythropoietin once a day for five days starting 45 minutes after burn injury (500 IU/kg body weight: EPO 500 or 2500 IU/kg body weight: EPO 2500).
  
  
  RESULTS
  Secondary burn progression-both in depth (histology) and in surface (planimetry)-as well as interspace perfusion (laser Doppler flowmetry) and hematocrit were analyzed. Further, dilatory response (inducible nitric oxide synthase expression), inflammation (leukocyte count), and angiogenesis (CD31 expression) were assessed. Finally, wound healing time and contracture rate were reported. Burn progression resulted in complete dermal destruction as well as in important interspace necrosis in control animals, whereas burn progression was significantly reduced in a dose-dependent manner in animals treated with erythropoietin. Tissue protection was associated with an increased interspace perfusion with EPO 500, but not with EPO 2500, and was paralleled by a significant increase in inducible nitric oxide synthase expression and decreased inflammation, independent of the erythropoietin dosage. EPO 2500 led to a significant increase of hematocrit at day 4. Finally, faster wound healing and less contracture were observed in animals treated with EPO 500 only.
  
  
  CONCLUSIONS
  Erythropoietin represents an easy-to-use therapeutic approach to prevent secondary burn progression, i.e., to control damage after burn injury. It preserves microcirculatory perfusion within the endangered areas in a dose-dependent manner.
authors: Faculty of Medicine, University of Geneva, and Division of Plastic, Reconstructive & Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland.
authors: Mickaël
authors: M
authors: Tobalem
authors: Yves
authors: Y
authors: Harder
authors: Farid
authors: F
authors: Rezaeian
authors: Reto
authors: R
authors: Wettstein
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009336:Necrosis / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004921:Erythropoietin