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John J Lopez, Roger J. Laham, Alon Stamler, Justin D Pearlman, Stuart Bunting, Aaron Kaplan, Joseph P Carrozza, Frank W Sellke, Michael Simons, VEGF administration in chronic myocardial ischemia in pigs, Cardiovascular Research, Volume 40, Issue 2, November 1998, Pages 272–281, https://doi.org/10.1016/S0008-6363(98)00136-9
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Abstract
Objective: Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single bolus or local intracoronary delivery. Methods: Yorkshire pigs underwent placement of a left circumflex artery ameroid occluder. Three weeks later the animals were randomized to treatment with VEGF (20 μg) accomplished by local intracoronary delivery system (InfusaSleeve™, n=10), intracoronary bolus infusion (n=7) or by epicardial implantation of an osmotic delivery system (n=7). An additional group of animals received intracoronary administration of saline and served as a control (n=9). Three weeks after initiation of therapy, the animals were evaluated with regard to myocardial perfusion and global as well as regional ventricular function. Results: All three VEGF treatment groups but not the control animals demonstrated a significant increase in the left-to-left (but not right-to-left) collateral index, myocardial blood flow (pre-therapy LCX vs. LAD (average of all groups): 0.76±0.35 vs. 0.96±0.38 ml*min−1*g−1, p=0.03; post-therapy: LCX vs. LAD: 1.16±0.39 vs. 1.15±0.28 ml*min−1*g−1, p=NS) and coronary vasodilatory reserve 3 weeks after growth factor administration. The observed increase in VEGF-induced perfusion correlated with improvement in regional ventricular function in all VEGF-treated groups (pre-therapy vs. post-therapy: i.c. VEGF 20±5.1 vs. 33±4.8; local VEGF 16±2.8 vs. 33.6; pump VEGF 17±3.8 vs. 34±4.9 p<0.05 for all) but not control animals (21±3.3 vs. 27±5.8, p=NS). Conclusion: Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.
