Therapeutic site selection is important for the successful development of collateral vessels.
Therapeutic site selection is important for the successful development of collateral vessels.
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DOI：
10.1016/j.jvs.2014.02.004
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发表时间：
2015-07
影响因子：
4.3
通讯作者：
A. Nishiyama;H. Koyama;T. Miyata;Toshiaki Watanabe
中科院分区：
文献类型：
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作者：
A. Nishiyama;H. Koyama;T. Miyata;Toshiaki Watanabe
背景诱导侧支循环发育以改善组织灌注率是治疗动脉闭塞性疾病的一种很有前途的方法。据报道，几种生长因子和细胞可以增加侧支循环；然而，这些因子和细胞的合适传递部位尚不清楚。在本研究中，我们确定了生长因子在兔肢体缺血模型中的传递部位，并评价了碱性成纤维细胞生长因子(碱性成纤维细胞生长因子)特异性传递到该部位是否能促进侧支循环的增加。28天后，进行血管造影，以确定该模型侧支循环发育的典型模式。随后，选择性地将碱性成纤维细胞生长因子(100gμg)注射到左侧尾骨股肌肉(尾骨组)或内收肌(内收肌组)，邻近的大腿主要肌肉。结果血管造影结果显示，股动脉切除后，左侧尾股肌侧支血管普遍发育，而左侧内收肌侧支血管较少。注射后28天，尾骨组小腿血压比值(左/右压)显著高于内收肌组(分别为0.85±0.05和0.69±0.05；P<；0.01)。在髂内动脉血流量(静息：24.6±6.1vs 17.4±8.0；最大值：47.4±12.3vs 33.2±10.7)和血管造影评分(0.67±0.13 vs 0.39±0.11；P<；0.01)方面也观察到类似的结果。免疫组织化学结果显示，尾骨组较内收肌组有明显的Ki-67、单核细胞趋化蛋白1和成纤维细胞生长因子受体1的表达。第14天时同一肌肉的形态计量学分析还显示，与内收肌组相比，尾骨组侧支血管密度和壁厚显著增加。结论选择性bFGF尾股肌注射较内收肌注射显著改善侧支血管发育和肢体血流灌注，提示部位选择在提高疗效中起重要作用。
BackgroundInduction of collateral development to improve tissue perfusion is a promising approach for the treatment of arterial occlusive diseases. Several growth factors and cells have been reported to increase collateral circulation; however, the appropriate site for the delivery of these factors and cells is unclear. In this study, we identified the delivery site for growth factor in a rabbit model of limb ischemia and evaluated whether specific delivery of basic fibroblast growth factor (bFGF) to this site enhanced collateral augmentation.MethodsThe left femoral artery of Japanese white rabbits was excised to induce limb ischemia. Twenty-eight days thereafter, angiograms were obtained to identify the typical pattern of collateral development in this model. Subsequently, bFGF (100 μg) was selectively injected into the left coccygeofemoral muscle (coccygeo group) or adductor muscle (adductor group), major thigh muscles in proximity. Collateral development was evaluated at 28 days after injection, and its mechanism was assessed by immunologic and morphometric analyses of muscle samples.ResultsAngiographic evaluation of this model revealed that after femoral artery excision, collateral vessels generally developed in the left coccygeofemoral muscle, whereas few collateral vessels were detected in the left adductor muscle. At 28 days after injection, calf blood pressure ratio, defined as left pressure to right pressure, was significantly higher in the coccygeo group than in the adductor group (0.85 ± 0.05 vs 0.69 ± 0.05, respectively;P< .01). Similar results were observed in blood flow through the internal iliac artery (resting: 24.6 ± 6.1 vs 17.4 ± 8.0 mL/min,P< .01; maximum: 47.4 ± 12.3 vs 33.2 ± 10.7 mL/min,P< .01) and in the angiographic score (0.67 ± 0.13 vs 0.39 ± 0.11;P< .01). Immunologic analyses of the coccygeofemoral muscle at day 3 showed marked expressions of Ki-67, monocyte chemotactic protein 1, and FGF receptor 1 in the coccygeo group compared with the adductor group. Morphometric analyses of the same muscle at day 14 also revealed that collateral vessel density and wall thickness were significantly increased in the coccygeal group compared with the adductor group.ConclusionsThese findings demonstrated that selective bFGF delivery to the coccygeofemoral muscle markedly improved collateral development and limb perfusion compared with delivery to the adductor muscle, suggesting that site selection is important in increasing therapeutic efficacy.