Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia

OBJECTIVES We sought to optimize vascular edothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens. BACKGROUND Although VEGF(165) is one of the most potent pro-angiogenic growth factors, VEGF(165) treatment for myocardial ischemia has been hampered by low efficacy and dose-limiting hypotension after systemic or intracoronary delivery. METHODS This study evaluated the effect of intravenous or intracornary rhVEGF(165) in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty-two Yorkshire pigs with chronically occluded left circumflex coronary arteries wre randomly assigned to receive 10 mug/kg of VEGF(165) :1) rapid (40 min) intravenous VEGF(165) 0.25 mug/kg/min, 2) slow (200 min) intravenous VEGF(165) 0.05 mug/kg/min, 3) rapid intracoronary VEGF(165) 0.25 mug/kg/min, 4) rapid intracoronary VEGF(165) 0.25 mug/kg/min + nitro-L-arginine methyl esdter hydrochloride (L-NAME) or 5) rapid vehicle infusion. RESULTS Intracoronary and intravenous VEGF(165) induced hypotension. Intracoronary VEGF-induced hypotension was blocked by L-NAME . Coronary angiography three weeks after treatment showed improvement in collateral index in both intracoronary groups but not the intravenous VEGF(165) groups. Likewise, myocardial blood flow and microvascular function in the ischemic territory improved in both intracoronary groups but not in the intravenous groups. CONCLUSIONS Intracoronary infusion of VEGF(165) significantly improves blood flow to the ischemic myocardium. Concomitant administration of L-NAME inhibits VEGF-induced hypotension while most likely preserving VEGF-induced angiogenesis. Intravenous infusion of VEGF(165) was not effective in augmenting either myocardial flow or function in this model. (C) 2001 by the American College of Cardiology.