title: Erythropoietin protects the central nervous system during prolonged hypothermic circulatory arrest: an experimental study in a canine model.
abstract: OBJECTIVE
  Current data suggest that erythropoietin protects the brain and the spinal cord from ischemic and traumatic injury. In this study, we determined whether erythropoietin protects the central nervous system during prolonged hypothermic circulatory arrest in an experimental canine model.
  
  
  METHODS
  Ten adult beagle dogs were randomly and intravenously injected with either 5000 U/kg recombinant human erythropoietin or normal saline. Each dog was then subjected to a cardiopulmonary bypass and 120 minutes of deep hypothermic circulatory arrest (18 degrees C). The level of tau proteins in the cerebrospinal fluid, a modified marker of neurologic deficit in dogs, and the histopathologic characteristics of the brains and spinal cords were then examined.
  
  
  RESULTS
  The level of tau proteins was significantly lower in the erythropoietin-treated group than in the untreated group at 6 hours (20 +/- 12 vs 144 +/- 54 pg/mL; P = .036) and 12 hours (64 +/- 35 vs 478 +/- 103 pg/mL; P = .01) after the operation. The total Neurologic Deficit Score was 59 +/- 31 (0, normal; 500, brain death) in the erythropoietin-treated group, compared with 376 +/- 30 in the untreated group (P = .0117). Histopathologic examination revealed that ischemic neuronal changes and apoptosis in the hippocampus CA1 were significantly lower in the erythropoietin-treated group (P < .01 and P = .028, respectively).
  
  
  CONCLUSIONS
  This study showed that erythropoietin protected the central nervous system during prolonged hypothermic circulatory arrest, partly by preventing both necrosis (ischemic neuronal changes) and apoptosis.
authors.affiliation: Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. mkawata-ths@umin.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitahori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsukihara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Morota
authors.forename: Minoru
authors.initials: M
authors.lastname: Ono
authors.forename: Noboru
authors.initials: N
authors.lastname: Motomura
authors.forename: Arata
authors.initials: A
authors.lastname: Murakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suematsu
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D004285:Dogs; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D008297:Male; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin