The effect of vascular endothelial growth factor on angiogenesis. An experimental study

Objective: to evaluate the effects of exogenous vascular endothelial growth factor (VEGF) on angiogenesis in a rabbit model of persistent hind limb is chaemia. Materials and methods: ischaemia was induced ill the hind limbs of 42 Neu, Zealand white rabbits divided into six groups, each of 7 animals. Group 1a and 1b received intramuscular injections of 1 and 2 mg VEGF/day, respective ly, into the ischaemic hind limb for 10 days beginning on postoperative 11t h day, and group 1c received IM injections of saline only. Group 2a and 2b received similar regimen of VEGF, but administered intra-arterially. Group 2c served as Controls. Perfusion of the ischaemic limb was evaluated by thi gh blood pressure and thigh circumference at 10, 25 acid 40 days following limb ischaemia ill all animals and by digital subtraction angiography, perf usion scans, histological examination of capillary density ill 2 animals fr om each group. Results: thigh pressure index and thigh circumference improved significantl y in the VEGF treated animals (Groups la, b and 2a,b). Collateral formation , as assessed by angiography, scintigraphy and by histological examination, indicated marked formation of collaterals ill the VEGF treated animals as compared with the controls. This was most pronounced ill groups receiving t he highest dose of VEGF. Conclusion: these data suggest that VEGF promotes angiogenesis, that the ro ute of administration is unimportant, but that a dose-response relationship is present in this experimental ischaemic hind limb model.