Efficacy and specificity of bFGF increased collateral flow in experimentalperipheral arterial insufficiency

Angiogenic growth factors could prove to be useful in managing peripheral a rterial insufficiency. The present study was designed to evaluate the dose response of basic fibroblast growth factor (bFGF), the efficacy of critical routes and dosing regimens, and the specificity of action in rats with per ipheral arterial insufficiency. Bilateral ligation of femoral arteries grea tly reduces blood flow capacity to the calf muscles but does not impair res ting flow needs. Collateral blood flow to calf muscles was determined 16 da ys postocclusion, during treadmill running, with Sr-85 and Ce-141 microsphe res, in blinded-randomized trials that included intraarterial and intraveno us infusions and subcutaneous injections of recombinant human bFGF. Peak bl ood flow of 75-80 ml . min(-1) . 100 g(-1) for calf muscle was observed at a bFGF dose of 5 mu g . kg(-1) . day(-1) (ia for 14 days) compared with 50 ml . min(-1) . 100 g(-1) for vehicle groups. Similar increases in collatera l blood flow were observed with short-term or prolonged and continuous or i ntermittent delivery of bFGF by any route. Collateral blood flows were simi lar in corresponding muscles across both limbs. Vascular remodeling induced by bFGF required attendant vascular occlusion, inasmuch as vessels in the normal nonoccluded vascular tree were unresponsive to circulating bFGF. Imp rovement in collateral blood flow with exogenous bFGF is robust, amenable t o short-term administration, and requires vascular occlusion to be effectiv e.