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.

Abstract:The intramuscular (IM) injection of a modi ed brin 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 brin 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 (L-CBP) 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 postsurgery 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/mm 2 ) to 292 6 12.4/mm 2 in the FDEF group (p , 0.05), but decreased in the control group to 98.7 6 7.7/mm 2 . 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.

The effects of electrical stimulation (ES) on arteriogenesis (the opening of preexisting collaterals) and angiogenesis (formation of new capillaries) were studied after acute bilateral hind limb ischemia was induced via bilateral femoral artery excision in a rabbit model. The study evaluated the rabbit hind limbs' normal response to acute ischemia and to application of ES by calculating changes in arterial and capillary densities. Comparisons were made with our prior study, in which the femoral artery was unilaterally excised, as we attempted to expand on the topics of arteriogenesis and angiogenesis. Twelve adult New Zealand white rabbits were randomly assigned to 1 of 2 series. In Series 1, the control group, both femoral arteries were excised and no ES was applied. In Series 2, both femoral arteries were excised and ES was applied to the left limb. One lead was implanted into the left adductor muscle near the site of the excised left femoral artery (Series 2), and a stimulator (Thera, Medtronic, Inc, Minneapolis, MN) was implanted in a separate pocket. ES was applied at a rate of 3 V, 30 contractions per minute, beginning immediately after surgery and continuously for 1 month. Angiography was performed in all 12 rabbits 1 month after surgery to establish the anatomy of the collateral vessels and to demonstrate that the femoral artery stump continued to be an end artery. Contrast-opacified arteries (COAs) that crossed the grid's midline, and the total number of grid lines intersected by COAs, were tallied according to an established method. Capillary density was calculated as the number of capillaries per square millimeter of muscle. In Series 1, after 1 month, the number of COAs crossing the grid's midline was 4.5 +/-1.5 on the left and 4.8 +/-1.2 on the right side. In Series 2, the number of COAs crossing the grid's midline was 7.9 +/-1.8 on the left side (p<0.05 vs Series 1) and 5.9 +/-1.6 on the right side of the same rabbit (p=NS vs Series 1). In Series 1, 36.7 +/-5.4 and 30.5 +/-7.7 total intersections were crossed by COAs on the left and right sides, respectively. In Series 2, total grid intersections crossed by COAs were 48.4 +/-8.5 and 47.5 +/-9.1 in the left and right sides, respectively (p<0.001 vs series 1). Baseline capillary density before femoral artery excision was 180.2 +/-21.3/mm(2). The capillary densities on the left sides were 94.2 +/-19.1 and 264.5 +/-7.6 in Series 1 and 2, respectively (p<0.001). The right sides showed a similar pattern with capillary densities of 88.5 +/-37.2 and 135.8 +/-6.8 (p<0.05) in Series 1 and 2, respectively. When capillary density was compared on the left and right sides of the same rabbit in Series 2, a statistically significant increase was also found; 264.5 +/-7.6 vs 135.8 +/-6.8 (p<0.001) in the left and right sides, respectively. Comparisons of the effect of electrical stimulation and the body's normal physiologic response to acute ischemia revealed a significant increase in the opening of preexisting collaterals (arteriogenesis) and the promotion of capill...

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The irradiation of large surfaces or whole body with copper vapor or ultraviolet lasers causes the structural ch&iges of the bone marrow skin and intestine cells indicate the acceleration of their prolif eration and differentiation. The increase of migration of the bone marrow cells in stroma and epithelial layers of organs indicates the iritensification of intercellular iritertissue interactions. This phenomena take place in doses not more th&i O2 3/cm2 for ultraviolet &id 0,5 J/cm4 for copper vapor lers. The greater of the doses cause the damages of bone marrow, skin and intestinal cells.