Adeno-associated viral vector-encoding vascular endothelial growth factor gene: effect on cardiovascular MR perfusion and infarct resorption measurements in swine.

Abstract

To prospectively determine in swine the effects of cardiac-specific and hypoxia-inducible vascular endothelial growth factor (VEGF) expression gene on angiogenesis and arteriogenesis by using cardiovascular magnetic resonance (MR) imaging for evaluation of infarct resorption and left ventricular (LV) function. The investigation conformed to U.S. National Institutes of Health guidelines. Twelve pigs with reperfused infarcts were studied with cardiovascular MR 3 days and 8 weeks after surgery. In six pigs, adeno-associated viral (AAV) vector-encoding VEGF (AAV-VEGF) gene was injected at eight sites 1 hour after reperfusion. Six pigs served as controls. Cardiovascular MR measurements of perfusion, area at risk, infarct size, and LV function were used in evaluation of the therapy. Hematoxylin-eosin, Masson trichrome, and biotinylated isolectin B4 stains were used to assess regional vascular density. Two-way Student t test was used to determine significant differences between means. AAV-VEGF had no effect on cardiovascular MR perfusion or infarct size measurements 3 days after infarction. At 8 weeks, the therapy increased infarct resorption, perfusion, and vascular density and prevented deterioration of ejection fraction in treated animals. These changes were associated with a significantly greater reduction in extent of enhanced region in treated (18.6% of LV surface area +/- 1.5 [standard error of mean] to 9.8% +/- 1.1) than in control animals (17.7% +/- 1.8 to 14.5% +/- 1.5, P = .028). Histopathologic findings in treated animals showed increased capillary and arterial density in infarct and periinfarct regions. These new vessels were active and thin-walled compared with thick-walled vessels of control animals. AAV-VEGF improves cardiovascular MR measurement of regional myocardial perfusion and LV function.