Efficacy of intracoronary or intravenous VEGF(165) in a pig model of chronic myocardial ischemia

OBJECTIVES We sought to optimize vascular edothelial growth factor (VEGF) t reatment for therapeutic angiogenesis in myocardial ischemia, we explored t he efficacy of five different regimens. BACKGROUND Although VEGF(165) is one of the most potent pro-angiogenic grow th factors, VEGF(165) treatment for myocardial ischemia has been hampered b y low efficacy and dose-limiting hypotension after systemic or intracoronar y delivery. METHODS This study evaluated the effect of intravenous or intracornary rhVE GF(165) in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty-two Yorkshire pig s with chronically occluded left circumflex coronary arteries wre randomly assigned to receive 10 mug/kg of VEGF(165) :1) rapid (40 min) intravenous V EGF(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 intracor onary VEGF(165) 0.25 mug/kg/min + nitro-L-arginine methyl esdter hydrochlor ide (L-NAME) or 5) rapid vehicle infusion. RESULTS Intracoronary and intravenous VEGF(165) induced hypotension. Intrac oronary VEGF-induced hypotension was blocked by L-NAME . Coronary angiograp hy three weeks after treatment showed improvement in collateral index in bo th 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 bloo d flow to the ischemic myocardium. Concomitant administration of L-NAME inh ibits VEGF-induced hypotension while most likely preserving VEGF-induced an giogenesis. Intravenous infusion of VEGF(165) was not effective in augmenti ng either myocardial flow or function in this model. (C) 2001 by the Americ an College of Cardiology.