Efficacy of Therapeutic Angiogenesis by Intramyocardial Injection of pCK-VEGF165 in Pigs

Abstract

Intramyocardial injection of vascular endothelial growth factor (VEGF) plasmid DNA was studied to demonstrate improvement of regional myocardial function. Twenty-one pigs that had undergone ligation of the left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF165 (VEGF group) or pCK-Null (control group) into the ischemic border zone. Electrocardiogram-gated single-photon emission computed tomography was performed 30 and 60 days after the coronary ligation. Segmental variables of perfusion and function were automatically quantified using a 20-segment model. In the segmental analysis, 119 segments were selected for analysis (71 segments in the VEGF group; 48 segments in the control group). Histologic analysis was also performed in the myocardial tissue of the ischemic border zone. At day 30, there were no significant differences in segmental perfusion, wall thickening, and wall motion between the two groups. In the VEGF group, all variables of perfusion, wall thickening, and wall motion were significantly improved at day 60 compared with those at day 30 (p < 0.05), while there were no differences in the control group. At day 60, perfusion (p = 0.018), wall motion (p = 0.004), and wall thickening (p = 0.068) of the VEGF group were improved compared with those of the control group. Histologic analysis showed that microcapillary density was significantly higher in the VEGF group than the control group (p < 0.001). Intramyocardial injection of pCK-VEGF165 significantly augmented neoangiogenesis in the ischemic area and improved regional myocardial function as well as myocardial perfusion.