title: Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2 months of coronary artery occlusion.
abstract: BACKGROUND
  In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15 days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI.
  
  
  METHODS
  Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8 mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60 days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied.
  
  
  RESULTS
  Infarct size was 30% smaller in pVEGF-treated sheep (23.6 ± 1.9% versus 32.7 ± 2.7% of the LV; p < 0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors.
  
  
  CONCLUSIONS
  In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.
authors.affiliation: Department of Physiology, Favaloro University, Buenos Aires, Argentina.
authors.forename: Gustavo L
authors.initials: GL
authors.lastname: Vera Janavel
authors.forename: Andrea
authors.initials: A
authors.lastname: De Lorenzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Cortés
authors.forename: Fernanda D
authors.initials: FD
authors.lastname: Olea
authors.forename: Patricia
authors.initials: P
authors.lastname: Cabeza Meckert
authors.forename: Andrés
authors.initials: A
authors.lastname: Bercovich
authors.forename: Marcelo
authors.initials: M
authors.lastname: Criscuolo
authors.forename: Rubén
authors.initials: R
authors.lastname: Laguens
authors.forename: Alberto
authors.initials: A
authors.lastname: Crottogini
mesh_terms: D000818:Animals; D054059:Coronary Occlusion / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D016277:Ventricular Function, Left
chemical_list: D042461:Vascular Endothelial Growth Factor A