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

Summary

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 infarctleft ventricular remodelingapoptosiserythopoietin

Abbreviations:

rhEPO

human recombinant erythropoietin

AAR

myocardial area at risk

MI

myocardial infarction

LV

left ventricular

EDV

end-diastolic volume

ESV

end-systolic volume

EF

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