Deferoxamine-fibrin accelerates angiogenesis in a rabbit model of peripheral ischemia

Abstract

The intramuscular (IM) injection of a modified fibrin meshwork plus deferoxamine was tested in a rabbit model of acute hind-limb ischemia. After excision of the left external iliac and femoral arteries, 12 rabbits at the Milwaukee Heart Institute were divided into two groups: control and fibrin meshwork plus deferoxamine (FDEF) IM. The rabbits underwent angiography before surgery, immediately after, and 1 month postoperatively. These data were compiled through counting by means of a grid overlay. Another 12 rabbits at the Vakhidov Center of Surgery, which did not undergo angiography, underwent lower limb-calf blood pressure (LCBP) measurements made immediately after surgery and at postoperative days 10, 20 and 30. Biopsies from thigh skeletal muscles of rabbits that had L-CBP measurements underwent alkaline phosphatase staining on day 30 to determine the percentage of biopsied area that was occupied by capillaries. The number of arteries and arterioles crossing 71 grid intersections immediately post-surgery decreased from 30.2 6 2.3 to 18.0 6 2.0 (p, 0.05). One month post-surgery this number increased to 29.2 6 2.4 in controls (p, 0.05 vs immediately post-surgery) and to 59.6 6 3.2 in the FDEF group (p, 0.001 vs immediately post-surgery). By day 30 the L-CBP ratio improved in the FDEF group (0.8 6 0.02) vs controls (0.3 6 0.04). By day 30 the capillary density increased from that of normal muscle tissue (198.6 6 12.9/mm2) to 292 612.4/mm2 in the FDEF group (p, 0.05), but decreased in the control group to 98.7 6 7.7/mm2. IM injection of FDEF considerably accelerated angiogenesis in severely ischemic hind-limb tissue in this model, making it a viable treatment method for clinical use in patients who have critical limb ischemia.