Cardiovascular Drugs and Therapy

, Volume 19, Issue 4, pp 243–250

Cardioprotection by Recombinant Human Erythropoietin Following Acute Experimental Myocardial Infarction: Dose Response and Therapeutic Window

  • Chanil Moon
  • Melissa Krawczyk
  • Doojin Paik
  • Edward G. Lakatta
  • Mark I. Talan
Basic Pharmacology

DOI: 10.1007/s10557-005-3189-6

Cite this article as:
Moon, C., Krawczyk, M., Paik, D. et al. Cardiovasc Drugs Ther (2005) 19: 243. doi:10.1007/s10557-005-3189-6


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.

Method and 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 3000 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.

Conclusion: 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.

Key Words

myocardial infarct left ventricular remodeling apoptosis erythopoietin 



human recombinant erythropoietin


myocardial area at risk


myocardial infarction


left ventricular


end-diastolic volume


end-systolic volume


ejection fraction

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Chanil Moon
    • 1
  • Melissa Krawczyk
    • 1
  • Doojin Paik
    • 2
  • Edward G. Lakatta
    • 1
  • Mark I. Talan
    • 1
  1. 1.Laboratory of Cardiovascular SciencesGerontology Research Center, National Institute on AgingBaltimoreUSA
  2. 2.Department of Anatomy and Cell BiologyHanyang UniversitySeoul 133-791Korea
  3. 3.Senior Investigator, Head, The Cardiovascular Gene Therapy Unit, Laboratory of Cardiovascular SciencesIntramural Research Program, National Institute on AgingBaltimoreUSA

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