HEMODYNAMIC-EFFECTS OF INTRACORONARY VEGF DELIVERY - EVIDENCE OF TACHYPHYLAXIS AND NO DEPENDENCE OF RESPONSE

Vascular endothelial growth factor (VEGF) has been utilized to improve blood flow in the setting of myocardial or peripheral vascular ischem ia. In this investigation we studied the hemodynamic effects of intrac oronary VEGF administration. Hemodynamic parameters and Doppler flow w ire recordings from the left anterior descending coronary artery were measured after intracoronary infusion of VEGF (1, 10, and 100 mu g) in 28 intubated pigs. Additional studies were performed using an in vitr o isolated microvessel preparation. VEGF produced a highly significant dose-dependent increase in coronary blood flow (maximal 3.51 +/- 0.85 -fold) in the absence of significant changes in epicardial artery diam eter, a decline in mean arterial pressure (maximal 43%), and a decreas e in left ventricular end-diastolic pressure (maximal 52%), all of whi ch could be inhibited by pretreatment with N-G-nitro-L-arginine. The i ncrease in coronary flow seen with 10 or 100 mu g VEGF was significant ly greater than the maximal vasodilation achieved with serotonin or ni troglycerin and was equivalent to a maximal adenosine response. In sum mary, VEGF stimulates nitric oxide (NO)-dependent dilation of coronary microvessels, and repeat administrations of VEGF resulted in rapid de velopment of tachyphylaxis to VEGF as well as serotonin, but not to ni troglycerin or adenosine, which appeared to be secondary to impaired N O production.