VEGF ADMINISTRATION IN CHRONIC MYOCARDIAL-ISCHEMIA IN PIGS

Objective: Previous investigations have shown the effectiveness of sus tained 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 circu mflex artery ameroid occluder. Three weeks later the animals were rand omized to treatment with VEGF (20 mu g) accomplished by local intracor onary delivery system (InfusaSleeve(TM) n = 10), intracoronary bolus i nfusion n = 7) or by epicardial implantation of an osmotic delivery sy stem (n = 7). An additional group of animals received intracoronary ad ministration of saline and served as a control (n = 9). Three weeks af ter initiation of therapy, the animals were evaluated with regard to m yocardial perfusion and global as well as regional ventricular functio n. Results: All three VEGF treatment groups but not the control animal s demonstrated a significant increase in the left-to-left (but not rig ht-to-left) collateral index, myocardial blood flow (pre-therapy LCX v s. LAD (average of all groups): 0.76 +/- 0.35 vs. 0.96 +/- 0.38 mlmin (-1)g(-1), p = 0.03; post-therapy: LCX vs. LAD: 1.16 +/- 0.39 vs. 1.1 5 +/- 0.28 mlmin(-1)*g(-1) p = NS) and coronary vasodilatory reserve 3 weeks after growth factor administration The observed increase in VE GF-induced perfusion correlated with improvement in regional ventricul ar 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; p ump VEGF 17 +/- 3.8 vs. 34 +/- 4.9 p<0.05 for all) but not control ani mals (21 +/- 3.3 vs. 27 +/- 5.8, p = NS). Conclusion: Single intracoro nary delivery (intravascular bolus or local delivery) of VEGF is effec tive in stimulating physiologically significant angiogenesis in porcin e model of chronic myocardial ischemia. (C) 1998 Elsevier Science B.V. All rights reserved.