Published Online
on December 31, 2001

A more recent version of this article appeared on February 12, 2002

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Submitted on October 15, 2001
Revised on November 27, 2001
Accepted on December 14, 2001

Myocardial Contrast Echocardiography Can Be Used to Assess the Microvascular Response to Vascular Endothelial Growth Factor-121

Flordeliza S. Villanueva MD^*, Judith A. Abraham PhD, George F. Schreiner MD, PhD, Melissa Csikari BS, David Fischer BS, James D. Mills MD, Ute Schellenberger PhD, Bryan J. Koci MS, and Joon S. Lee MD

From the Cardiovascular Institute (F.S.V., M.C., D.F., J.D.M., B.J.K., J.S.L.), University of Pittsburgh School of Medicine, Pittsburgh, Pa, and Scios Inc (J.A.A., G.F.S., U.S.), Sunnyvale, Calif.

^* To whom correspondence should be addressed. E-mail: villanuevafs{at}msx.upmc.edu.

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^-ßt]) used to derive indices of red cell velocity (ß) 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. ß 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.

Key words: echocardiography • angiogenesis • coronary disease

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