Efficacy and specificity of bFGF increased collateral flow in experimental peripheral arterial insufficiency

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Abstract
Angiogenic growth factors could prove to be useful in managing peripheral arterial 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 peripheral arterial insufficiency. Bilateral ligation of femoral arteries greatly reduces blood flow capacity to the calf muscles but does not impair resting flow needs. Collateral blood flow to calf muscles was determined 16 days postocclusion, during treadmill running, with 85Sr and 141Ce microspheres, in blinded-randomized trials that included intra-arterial and intravenous infusions and subcutaneous injections of recombinant human bFGF. Peak blood flow of 75–80 ml ⋅ min−1 ⋅ 100 g−1 for calf muscle was observed at a bFGF dose of 5 μg ⋅ kg−1 ⋅ day−1(ia for 14 days) compared with 50 ml ⋅ min−1 ⋅ 100 g−1 for vehicle groups. Similar increases in collateral blood flow were observed with short-term or prolonged and continuous or intermittent delivery of bFGF by any route. Collateral blood flows were similar 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. Improvement in collateral blood flow with exogenous bFGF is robust, amenable to short-term administration, and requires vascular occlusion to be effective.