title: Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window.
abstract: BACKGROUND
  Recombinant human erythropoietin (rhEPO) protects tissue from ischemic damage, but translation of this finding into useful guidelines with respect to human trials for myocardial infarction (MI) requires a determination of the minimum effective rhEPO dose and the therapeutic window following MI.
  
  
  RESULTS
  Serial echocardiography revealed that during four weeks following MI, induced by a permanent coronary ligation in rats, the LV end-diastolic and end-systolic volumes in untreated rats expanded from 0.35 +/- 0.01 and 0.14 +/- 0.01 ml to 0.84 +/- 0.04 and 0.61 +/- 0.06 ml, respectively, and ejection fraction (EF) reduced by 50%. A single i.v. injection of rhEPO immediately following MI in a dose of 150 IU/kg was as effective as 3,000 IU/kg in causing a 2-fold reduction of the number of apoptotic nuclei in the AAR 24-h later, a 2-fold reduction of the MI size measured 4 weeks later, attenuation of progressive LV dilatation and fall in EF. A 3000 IU/kg dose had similar therapeutic effects when delayed by 4, 8, or 12 h following MI, but was not effective after a 24-h delay. A single dose of 150 IU/kg was effective within 4 h post-MI, but was without effect if administered after an 8-h delay.
  
  
  CONCLUSIONS
  Cell death, final MI size, myocardial remodeling and functional decline are significantly reduced in rats by a single injection of rhEPO in a dose as low as 150 IU/kg if administered during the first 4 h after the ischemic event. Higher doses extend the therapeutic window up to 12 h.
authors.affiliation: Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, 21224, MD, USA.
authors.forename: Chanil
authors.initials: C
authors.lastname: Moon
authors.forename: Melissa
authors.initials: M
authors.lastname: Krawczyk
authors.forename: Doojin
authors.initials: D
authors.lastname: Paik
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Mark I
authors.initials: MI
authors.lastname: Talan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004452:Echocardiography; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
chemical_list: D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D004921:Erythropoietin