Hehrlein C, Gollan C, Dönges K, Metz J, Riessen R, Fehsenfeld P, von Hodenberg E, Kübler W
Department of Cardiology, University of Heidelberg, Germany.
Circulation. 1995 Sep 15;92(6):1570-5. doi: 10.1161/01.cir.92.6.1570.
Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model.
Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 microCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC alpha-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30 +/- 2% of SMCs in the neointima were proliferating, compared with 0.5 +/- 0.1% of SMCs after implantation of stents with an initial activity of 35 microCi (P < .001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation.
The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.
平滑肌细胞（SMC）迁移、增殖以及新生内膜增厚所导致的再狭窄限制了球囊血管成形术和支架植入术的临床成功率。在本研究中，通过低剂量放射性支架进行血管内照射对新生内膜形成的长期影响与传统支架植入术在兔模型中进行了比较。
Palmaz-Schatz支架在回旋加速器中被制成放射性的。这些支架的活性非常低（最大值为35微居里），因此，操作不需要广泛的辐射防护。在兔髂动脉植入非放射性支架和放射性支架后1周、4周、12周和52周，通过定量组织形态计量学分析新生内膜增厚情况。对内皮细胞血管性血友病因子、巨噬细胞、SMCα-肌动蛋白、I型胶原和增殖细胞核抗原（PCNA）进行免疫染色，以确定辐射引起的动脉壁变化。通过对PCNA免疫反应性细胞进行计算机辅助细胞计数来量化SMC增殖。在所有观察时间点，放射性支架植入均以剂量依赖方式显著抑制新生内膜形成。在非放射性支架植入后1周SMC增殖活性达到峰值时，新生内膜中30±2%的SMC在增殖，而初始活性为35微居里的支架植入后，SMC增殖比例为0.5±0.1%（P<0.001）。覆盖放射性支架的新生内膜的特征是平滑肌细胞数量减少和细胞外基质形成增加。此外，我们观察到内皮化延迟取决于辐射剂量。非放射性和放射性支架植入后血管血栓形成无差异。
本研究结果清楚地表明，低剂量放射性血管内支架能有效抑制兔体内SMC增殖和新生内膜增生。
