Effect of VEGF gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after two months of coronary artery occlusion.

VERA JANAVEL GL; DE LORENZI A; CORTÉS C; OLEA FD; CABEZA MECKERT P; BERCOVICH A; CRISCUOLO M; LAGUENS R; CROTTOGINI A

JOURNAL OF GENE MEDICINE

JOHN WILEY & SONS LTD

Año: 2012 vol. 14 p. 279 - 287

1099-498X

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