title: Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction.
abstract: BACKGROUND
  In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI.
  
  
  METHODS
  Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8).
  
  
  RESULTS
  Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect.
  
  
  CONCLUSIONS
  Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.
authors.affiliation: Department of Physiology, Favaloro University, Buenos Aires, Argentina.
authors.forename: Fernanda D
authors.initials: FD
authors.lastname: Olea
authors.forename: Andrea
authors.initials: A
authors.lastname: De Lorenzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Cortés
authors.forename: Luis
authors.initials: L
authors.lastname: Cuniberti
authors.forename: Lucía
authors.initials: L
authors.lastname: Fazzi
authors.forename: María del Pilar
authors.initials: Mdel P
authors.lastname: Flamenco
authors.forename: Paola
authors.initials: P
authors.lastname: Locatelli
authors.forename: Patricia
authors.initials: P
authors.lastname: Cabeza Meckert
authors.forename: Andrés
authors.initials: A
authors.lastname: Bercovich
authors.forename: Rubén
authors.initials: R
authors.lastname: Laguens
authors.forename: Alberto
authors.initials: A
authors.lastname: Crottogini
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015425:Myocardial Reperfusion / Q000379:methods*; D034561:Sheep, Domestic; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000235:genetics*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin