Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121

Abstract

Background - Therapeutic angiogenesis is a new approach to treating ischemic heart disease, and the optimal method for assessing its efficacy is unclear. We used myocardial contrast echocardiography (MCE) to evaluate the therapeutic response to the angiogenic agent, vascular endothelial growth factor-121 (VEGF121). Methods and Results - After placement of an ameroid constrictor (day 0) around the left anterior descending artery (LAD), dogs were given intracoronary VEGF121 protein (108 μg, n=6) or placebo (n=6) on days 7 and 21, and subcutaneous VEGF121 (1 mg) or placebo on days 8 to 20 and 22 to 27. On day 48, MCE was performed during rest and dobutamine stress. Videointensity (y) and pulsing interval (t) were fit to an exponential model (y=A[1-e-βt]) used to derive indices of red cell velocity (β) and capillary area (A), and parameters were compared with radiolabeled microsphere flow data. VEGF121 treatment resulted in higher resting left anterior descending artery/left circumflex flow ratio compared with placebo (P<0.03) and improved collateral flow reserve. β was 0.94±0.37 in VEGF121 dogs versus 0.38±0.31 in controls (P<0.02), with the greatest difference in the endocardium. The parameter A was comparable in both groups, suggesting that microvascular changes did not alter capillary cross-sectional area, and histology indicated a trend toward higher arteriolar density in VEGF121-treated animals. Conclusions - VEGF121 protein improves collateral flow and reserve. MCE can evaluate the transmural location and structural and functional responses of the microvasculature to angiogenic interventions.