Document Detail

Effect of VEGF gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after two months of coronary artery occlusion.
MedLine Citation:
PMID:  21954009     Owner:  NLM     Status:  Publisher    
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 and how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2 months-old ovine AMI. METHODS: Adult sheep with coronary artery occlusion were randomized to blindly receive 10 intramyocardial injections of 3.8 mg 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 vs. 32.7 ± 2.7% of the LV, p < 0.02). Percent 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, but the force-frequency relation 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. Copyright © 2011 John Wiley & Sons, Ltd.
Gustavo L Vera Janavel; Andrea De Lorenzi; Claudia Cortés; Fernanda D Olea; Patricia Cabeza Meckert; Andrés Bercovich; Marcelo Criscuolo; Rubén Laguens; Alberto Crottogini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-26
Journal Detail:
Title:  The journal of gene medicine     Volume:  -     ISSN:  1521-2254     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 John Wiley & Sons, Ltd.
Department of Physiology, Favaloro University, Buenos Aires, Argentina; Bio Sidus, Buenos Aires, Argentina.
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