Direct fibrin injection to promote new collateral growth in hind limb ischemia in a rabbit model.

Local stimulation of angiogenesis is a new approach for the treatment of critical limb ischemia. Our investigation tested intramuscular (IM) injection of a modified fibrin meshwork in a rabbit model. Methods: The left external iliac and femoral arteries were excised in 24 rabbits that were divided into four groups: control; IM saline injection; fibrin meshwork plus low dose (2.5 mg) fibrinogen IM; fibrin meshwork plus high-dose (5.0 mg) fibrinogen IM. Angiography was performed before surgery, immediately after surgery, and one month postoperatively. Lower limb-calf blood pressure was measured immediately after surgery and at postoperative days 10, 20, and 30. On day 30, conventional indirect immunostaining was performed to determine the percentage of the area occupied by capillaries. Results: Immediately after surgery, in all four groups, the number of contract-opacified arteries (COA) crossing a specific segment of a grid decreased from 5.3 ± 1.3 to 3.2 ± 1.0 (p 0.05 versus control and versus baseline data). When fibrin containing 5.0 mg fibrinogen was used, these parameters increased to 8.5 ± 0.9, 48.3 ± 5.1 , and 27.1 ± 0.9 , respectively ( p < 0.001 versus immediately after surgery and p < 0.05 versus control). In all four series, no Doppler flow signal was detected from the posterior tibial artery by day 10. By day 30, the lower limb-calf blood pressure ratio had improved in all four series, but was significantly improved in only the two groups treated with fibrin sealant ( 0.3 ± 0.05 control; 0.3 ± 0.08 saline; 0.6 ± 0.06 fibrinogen 2.5; 0.7 ± 0.05 fibrinogen 5.0). Conclusion: Intramuscular injection of a fibrin meshwork considerably increased angiogenesis in the severely ischemic hind limb and may be strongly recommended for clinical use in patients with limb-threatening ischemia.(J Card Surg 2002;17:502-511)