ENHANCED REVASCULARIZATION AFTER ANGIOGENIC STIMULATION IN A RABBIT MODEL OF BILATERAL LIMB ISCHEMIA

Objective: We previously demonstrated stimulation of collateral vessel formation in a rabbit model of unilateral limb ischaemia after admini stration of endothelial cell growth factor (ECGF). To distinguish clea rly the effects of ischaemia alone from those of ischaemia combined wi th angiogenic stimulation in the same animal, a model of bilateral hin dlimb ischaemia was used to evaluate further the angiogenic effect of ECGF. Design: Ischaemia was produced in both hindlimbs of II rabbits b y femoral artery excision. Beginning 10 days later, ECGF (8 mg in 3 mi of saline) was injected in one hindlimb while 3 mi of saline alone wa s injected in the other every other day for a fetal of five doses. Out come measures: Calf systolic blood pressure tons measured in both limb s on postoperative days 10, 30, and 50. On day 50, collateral formatio n teas quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies. Results: The mean calf systolic blood pressure in the both hindlimbs pins simi lar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was signific antly higher in the ECGF-treated limb on day 30 (68.9 +/- 3.1 versus 4 5.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0. 0001 for both comparisons). On day 50, collateral vessels were signifi cantly more numerous in the ECGF-treated limb (17.2 +/- 1.6 versus 11. 0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159 .6 +/- 12.9 per mm(2); p < 0.002). Conclusion: Local administration of ECGF enhanced collateral development leading to significantly improve d perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upr egulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.