^(103)Pd放射性支架在猪冠状动脉再狭窄模型中抑制新生内膜增殖的作用

Anti-proliferation effect of^(103) Pd radioactive stent in micro-porcine model with coronary restenosis

目的 研究1 0 3Pd放射性支架抑制新生内膜增殖的有效性、量效关系、时效关系 ,并观察该放射性支架的安全性。方法 采用微型猪冠状动脉再狭窄模型 ,比较不同活度1 0 3Pd支架组 (10 0 0μCi、5 0 0 μCi、10 0 μCi)和对照组在不同时间 (5周、12周 )的冠状动脉造影、形态测量学以及组织病理学结果。结果 5 0 0 μCi和 10 0 μCi的1 0 3Pd支架内的新生内膜面积显著低于对照组 ,10 0 0 μCi的1 0 3Pd支架内的新生内膜面积与对照组相似 ,5 0 0 μCi的1 0 3Pd支架内的新生内膜面积显著低于 10 0 μCi。与对照组相比 ,5 0 0 μCi的1 0 3Pd支架在 5周和 12周时分别使内膜面积减少 4 9%和 5 0 % ,10 0 μCi的1 0 3Pd支架抑制新生内膜增殖的效应在 12周时下降了 5 6 % (由 32 %减至 14 % )。 10 0 μCi的1 0 3Pd支架两端的新生内膜面积显著高于对照组 ,5 0 0 μCi和 10 0 0 μCi的1 0 3Pd支架两端的新生内膜面积与对照组相似。组织病理学检查未发现1 0 3Pd支架对受试动物产生明显的放射性损伤。结论 1 0 3Pd支架抑制内膜增殖的作用可能存在一个安全有效的剂量窗 ,1 0 3Pd支架抑制内膜增殖的效应具有剂量依赖性。适当活度的1 0 3Pd支架能有效地、持久地抑制内膜增殖且无毒副作用。这些结果提示1 0

Objective To investigate the effectiveness, dose-effect and time-effect relationships for inhibiting neointimal proliferation by 103 Pd radioactive stent, and the safety of the radioactive stent. Methods By angiogaphic, morphometric and histopathologic analysis, we compared 1?000 μCi, 500 μCi and 100 μCi 103 Pd stents with non-radioactive stents on 5 weeks and 12 weeks after stenting in a micro-porcine coronary model of restenosis. Results The neointimal areas of 500 μCi and 100 μCi 103 Pd stents were significantly smaller than control stents. 1?000 μCi stents and control stents had similar neointimal areas. The neointimal areas of 500 μCi stents were significantly smaller than 100 μCi stents. Compared with control stents, 500 μCi stents reduced the neointimal areas by 49% and 50% respectively on 5 weeks and 12 weeks after stenting. Compared with 5 weeks after stenting, the effect of inhibiting neointimal proliferation by 100 μCi stents was reduced by 56% (32% vs 14%) on 12 weeks. The neointimal areas on both edge of 100 μCi stents were significantly larger than control stents. The neointimal areas on both edge of 1?000 μCi stents and 500 μCi stents were similar with control stents. No evident radiation damage had been found in the experimental animals who had 103 Pd stent. Conclusion There may be an effective dose window for 103 Pd radioactive stent in inhibiting neointimal proliferation. The effect of inhibiting neointimal proliferation was dose dependent. 103 Pd radioactive stent with appropriate activities may effectively, persistently inhibit neointimal proliferation with no adverse radiation sequelae. These results suggest that 103 Pd radioactive stent prevent restenosis. These data may be useful in predicting safe and effective activity for 103 Pd radioactive stent.