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.
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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
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Moon, C., Krawczyk, M., Paik, D. et al. Cardioprotection by Recombinant Human Erythropoietin Following Acute Experimental Myocardial Infarction: Dose Response and Therapeutic Window. Cardiovasc Drugs Ther 19, 243–250 (2005). https://doi.org/10.1007/s10557-005-3189-6
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DOI: https://doi.org/10.1007/s10557-005-3189-6