In previous investigations, it was shown that applying a modest regimen of electrical stimulation (ES), even in severely ischemic tissue, improves the healing process, accelerates neovascularization, and enhances angiogenesis in muscle tissue. Our objective in this current report was to further understand ES as a potential alternative treatment for severe muscle ischemia. Immediately after the left distal external iliac artery and the femoral artery were excised, ES (30 contractions per minute [cpm], 2 V, single impulses per burst) was applied to rabbit adductor muscle near the site of the excised femoralis artery for 24 hours daily over 1 month. Three other series served as controls: ES without arterial excision; arterial excision without ES or lead implantation; and arterial excision with lead implantation but no ES. Histologic study of capillary density was performed by angiography (employing a grid template) and by measuring the lower limb-calf blood pressure ratio. At the end of 30 days in the ES series, 10.5 +/-1.2 contrast-medium opacified arteries (COAs) crossed a specific grid section segment compared with 7.2 +/-1.5 in the control series without ES (p<0.05); 68.2 +/-9.3 COAs crossed a grid section compared with 43.2 +/-6.4 in controls (p<0.05); 27.3 +/-1.2 grids contained COAs compared with 29.3 +/-3.5 in controls (p<0.05); lower limb-calf blood pressure ratio was 0.81 +/-0.06 compared with 0.31 +/-0.07 in controls (p<0.05); and capillary density was 283.7 +/-24.5 mm2 compared with 91.4 +/-20.9 mm2 in controls (p<0.001). These preliminary results show that cautious ES enhances and accelerates muscle revascularization in severely ischemic tissue.

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.