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

Purpose: 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. Materials and Methods: 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. Results: 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. Conclusion: AAV-VEGF improves cardiovascular MR measurement of regional myocardial perfusion and LV function. (c) RSNA, 2007.