Abstract
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/mm2. 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 capillary density (angiogenesis) with the use of electrical stimulation.
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