VASCULAR ENDOTHELIAL GROWTH-FACTOR ADMINISTRATION IN CHRONIC MYOCARDIAL-ISCHEMIA

Vascular endothelial growth factor (VEGF) is a potent mitogen capable of stimulating angiogenesis. We examined the effect of VEGF administra tion in a model of chronic porcine myocardial ischemia. Nineteen pigs were instrumented with proximal left circumflex coronary artery (LCX) Ameroid constrictors. in eight animals VEGF (2 mu g) with heparin (50 U) was administered extraluminally to the LCX myocardium with an osmot ic pump for 4 wk and 11 other animals served as controls. VEGF-treated animals demonstrated higher flow in the LCX territory during both res t and pacing compared with untreated controls (rest: 1.35 +/- 0.1 vs. 0.80 +/- 0.09 ml . min(-1). g(-1); pacing: 2.01 +/- 0.37 vs. 1.01 +/- 0.07 ml . min(-1). g(-1), P < 0.05, VEGF vs. controls). The observed i mprovement in regional coronary flow in VEGF-treated animals resulted in better preservation of endothelium-dependent microvessel relaxation as well as fractional LV shortening in the LCX territory during pacin g in the VEGF-treated than in control animals (controls: 7.1 +/- 2.6 v s. 3.6 +/- 2.0%, rest vs. pacing; VEGF: 6.9 +/- 2.9 vs. 6.3 +/- 2.9%, rest vs. pacing). We conclude that VEGF administration in a gradual co ronary occlusion model in pigs results in improvement of coronary flow and preservation of regional hemodynamics in the compromised myocardi um.