Therapeutic angiogenesis by intramuscular injection of fibrin particles into ischaemic hindlimbs

1. Fibrin gel has been used as a carrier of angiogenic molecules to promote neovascularization in animal models of limb ischaemia. However, little is known about the effects of fibrin itself under such pathological conditions. Accordingly, the present study tested the efficacy of fibrin in a rabbit model of acute hindlimb ischaemia. 2. Unilateral ischaemia was induced by resection of the left femoral artery. Seven days after surgery, fibrin particles (FP), which were free of fibrinogen, thrombin and vascular endothelial growth factor, were injected directly into the ischaemic thigh muscles. Twenty-four rabbits were divided into four groups, namely a control group receiving phosphate-buffered saline and three FP-treated groups receiving 5, 10 or 20 mg FP. 3. Collateral vessel development and limb perfusion were assessed by angiography, measuring the calf blood pressure ratio (BPR), thermographic scanning and the histological determination of capillary density. 4. At day 35 post-surgery, the treatment with 5 mg FP produced an augmentation of collateral vessel development (P < 0.01), increased numbers of capillaries (P < 0.05) and improved perfusion manifested by a higher blood flow (P < 0.01) and calf BPR (P < 0.05) compared with controls. Treatment with 10 and 20 mg FP had similar effects to those observed with 5 mg FP. 5. The present study reveals that FP promotes angiogenesis in a rabbit model of hindlimb ischaemia, thus providing a feasible approach to therapeutic angiogenesis in ischaemic diseases.