Enhanced revascularisation after angiogenic stimulation in a XXXX model of bilateral limb ischaemia.

@entity21349 @entity95 @entity291
OBJECTIVE: We previously demonstrated stimulation of collateral vessel formation in a @entity95 model of unilateral limb ischaemia after administration of endothelial cell growth factor ( @entity21349 ). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of @entity21349 . DESIGN: Ischaemia was produced in both hindlimbs of 11 @entity95 by femoral artery excision. Beginning 10 days later, @entity21349 (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses. OUTCOME MEASURES: @entity291 systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies. RESULTS: The mean @entity291 systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the @entity21349 -treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 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 significantly more numerous in the @entity21349 -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 mm2; p < 0.002). CONCLUSION: Local administration of @entity21349 enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.
