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.
authors.affiliation: Cardiology Department, Fondazione IRCCS Policlinico S Matteo, Pavia, Italy. m.ferrario@smatteo.pv.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrario
authors.forename: Eloisa
authors.initials: E
authors.lastname: Arbustini
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.forename: Nicola
authors.initials: N
authors.lastname: Marziliano
authors.forename: Claudia
authors.initials: C
authors.lastname: Raineri
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoletti
authors.forename: Gaetano Maria
authors.initials: GM
authors.lastname: De Ferrari
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Luigi
authors.initials: L
authors.lastname: Angoli
authors.forename: Ezio
authors.initials: E
authors.lastname: Bramucci
authors.forename: Barbara
authors.initials: B
authors.lastname: Marinoni
authors.forename: Marco
authors.initials: M
authors.lastname: Ferlini
authors.forename: Enza
authors.initials: E
authors.lastname: Moretti
authors.forename: Arturo
authors.initials: A
authors.lastname: Raisaro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Repetto
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000097:blood
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin