Vascular Regeneration by Repeated Infusions of Basic Fibroblast Growth Factor in a Rabbit Model of Hind-Limb Ischemia

Regenerative therapy is a new treatment of vascular occlusive diseases. The purpose of this study was to examine the advantages of repeated low-dose growth factor infusions compared with a single high-dose infusion in an ischemic hind-limb rabbit model. Thirty-two rabbits were used to construct an ischemic hind-limb model by resection of the left femoral artery. For the vascular regenerative method, basic fibroblast growth factor (bFGF) was impregnated into 3 mg of gelatin microspheres 30 microm in diameter and a reservoir system was implanted in the left femoral artery for infusion. The gelatin microspheres were then infused into the left internal iliac artery via the reservoir system. The rabbits were divided into three groups according to different infusion methods: single high-dose infusion, repeated low-dose infusions, and saline (control). Therapeutic effects were evaluated by thigh temperature, blood pressure, blood flow, angiography, and pathology. There was no significant difference between the two infusion methods in thigh temperature, blood pressure, blood flow, angiography, and pathology. In pathologic analyses at 2 and 4 weeks, both the repeated low-dose infusion and the single high-dose infusion groups showed significant differences in the number of vessels when compared with the control group. The efficacy of repeated bFGF infusions for neovascularization via the reservoir method was investigated. Despite the pathologic confirmation of neovascularization, there was no significant difference in treatment effect by the two administration methods.