BASIC FIBROBLAST GROWTH-FACTOR INCREASES COLLATERAL BLOOD-FLOW IN RATS WITH FEMORAL ARTERIAL LIGATION

The potential for exogenous infusion of basic fibroblast growth factor (bFGF) to increase collateral blood flow to dependent tissue was quan tified in adult male rats with peripheral arterial insufficiency; Occl usion of the femoral artery at a proximal site did not infringe on res ting blood flow to the distal hindlimb muscle, but did remove the bloo d flow reserve. Blood Row to the hindlimb muscles was measured with ra diolabeled microspheres using an isolated hindlimb preparation perfuse d in the descending aorta (Krebs-Henseleit bicarbonate, 5% albumin med ium containing red blood cells [40% hematocrit]) at 100 mm Hg. Calf mu scle blood now changed modestly (approximate to 50%) with infusion of only the carrier (heparin/saline) increased markedly over the first 2 weeks Of bFGF infusion (1 mu g/d into the femoral artery), but did not change further with infusion for 4 weeks. Waiting 2 weeks after 1 wee k of bFGF infusion did not further increase the intermediate improveme nt in blood flow. The improved collateral blood flow and increased mus cle capillary density likely contributed to the enhanced muscle perfor mance observed during nerve stimulation in situ. X-ray films of arteri al casts identified an expansion of upper thigh vessels that likely se rved as collaterals. In animals with peripheral arterial insufficiency , short-term exogenous infusion of bFGF is effective at inducing vascu lar expansion that is sufficient to improve the flow reserve of depend ent distal tissue and enhance muscle function. This raises the expecta tion that a similar response in patients with peripheral arterial insu fficiency would significantly improve morbidity, including the symptom s of intermittent claudication.