VEGF administration in chronic myocardial ischemia in pigs.

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 micrograms) 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.