title: Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs.
abstract: OBJECTIVE
  We investigated the effects of erythropoietin (EPO) on neovascularization and cardiac function after myocardial infarction (MI).
  
  
  BACKGROUND
  Erythropoietin exerts antiapoptotic effects and mobilizes endothelial progenitor cells (EPCs).
  
  
  METHODS
  We intravenously administered EPO (1,000 IU/kg) immediately [EPO(0) group], 6 h [EPO(6h) group], or 1 week [EPO(1wk) group] after the permanent ligation of the coronary artery in dogs. Control animals received saline immediately after the ligation.
  
  
  RESULTS
  The infarct size 6 h after MI was significantly smaller in the EPO(0) group than in the control group (61.5 +/- 6.0% vs. 22.9 +/- 2.2%). One week after MI, the circulating CD34-positive mononuclear cell numbers in both the EPO(0) and the EPO(6h) groups were significantly higher than in the control group. In the ischemic region, the capillary density and myocardial blood flow 4 weeks after MI was significantly higher in both the EPO(0) and the EPO(6h) groups than in the control group. Four weeks after MI, left ventricular (LV) ejection fraction in the EPO(6h) (48.6 +/- 1.9%) group was significantly higher than that in either the control (41.9 +/- 0.9%) or the EPO(1wk) (42.6 +/- 1.2%) group but significantly lower than that in the EPO(0) group (56.1 +/- 2.3%). The LV end-diastolic pressure 4 weeks after MI in both the EPO(0) and the EPO(6h) groups was significantly lower than either the control or the EPO(1wk) group. Hematologic parameters did not differ among the groups.
  
  
  CONCLUSIONS
  In addition to its acute infarct size-limiting effect, EPO enhances neovascularization, likely via EPC mobilization, and improves cardiac dysfunction in the chronic phase, although it has time-window limitations.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Wakeno
authors.forename: Masafumi
authors.initials: M
authors.lastname: Myoishi
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Okada
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shiraga
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002196:Capillaries / Q000033:anatomy & histology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004921:Erythropoietin / Q000627:therapeutic use*; D006439:Hemodynamics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
chemical_list: D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin