High-dose erythropoietin in patients with acute myocardial infarction: A pilot, randomised, placebo-controlled study

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Abstract

Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10 3 IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalInternational Journal of Cardiology
Volume147
Issue number1
DOIs
Publication statusPublished - Feb 17 2011

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Erythropoietin
Myocardial Infarction
Placebos
Percutaneous Coronary Intervention
Blood Cells
Gene Expression
vpr Genes
Vascular Endothelial Growth Factor Receptor-2
Myocardial Reperfusion
Ventricular Remodeling
Cell Size
Caspase 3
Anti-Inflammatory Agents
Magnetic Resonance Spectroscopy
Blood Platelets
Morbidity
Mortality
Therapeutics
Genes

Keywords

  • Acute myocardial infarction
  • Erythropoietin
  • Percutaneous coronary intervention
  • Progenitor cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{e5e8b84cedd44124866c42a0d01480b6,
title = "High-dose erythropoietin in patients with acute myocardial infarction: A pilot, randomised, placebo-controlled study",
abstract = "Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10 3 IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30{\%} reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.",
keywords = "Acute myocardial infarction, Erythropoietin, Percutaneous coronary intervention, Progenitor cells",
author = "Maurizio Ferrario and Eloisa Arbustini and Margherita Massa and Vittorio Rosti and Nicola Marziliano and Claudia Raineri and Rita Campanelli and Alessandra Bertoletti and {De Ferrari}, {Gaetano Maria} and Catherine Klersy and Luigi Angoli and Ezio Bramucci and Barbara Marinoni and Marco Ferlini and Enza Moretti and Arturo Raisaro and Alessandra Repetto and Schwartz, {Peter J.} and Luigi Tavazzi",
year = "2011",
month = "2",
day = "17",
doi = "10.1016/j.ijcard.2009.10.028",
language = "English",
volume = "147",
pages = "124--131",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - High-dose erythropoietin in patients with acute myocardial infarction

T2 - A pilot, randomised, placebo-controlled study

AU - Ferrario, Maurizio

AU - Arbustini, Eloisa

AU - Massa, Margherita

AU - Rosti, Vittorio

AU - Marziliano, Nicola

AU - Raineri, Claudia

AU - Campanelli, Rita

AU - Bertoletti, Alessandra

AU - De Ferrari, Gaetano Maria

AU - Klersy, Catherine

AU - Angoli, Luigi

AU - Bramucci, Ezio

AU - Marinoni, Barbara

AU - Ferlini, Marco

AU - Moretti, Enza

AU - Raisaro, Arturo

AU - Repetto, Alessandra

AU - Schwartz, Peter J.

AU - Tavazzi, Luigi

PY - 2011/2/17

Y1 - 2011/2/17

N2 - Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10 3 IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

AB - Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10 3 IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

KW - Acute myocardial infarction

KW - Erythropoietin

KW - Percutaneous coronary intervention

KW - Progenitor cells

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U2 - 10.1016/j.ijcard.2009.10.028

DO - 10.1016/j.ijcard.2009.10.028

M3 - Article

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AN - SCOPUS:79951722690

VL - 147

SP - 124

EP - 131

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

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