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使用发射β粒子的支架进行低剂量照射抑制新生内膜增殖。

Inhibition of neointimal proliferation with low-dose irradiation from a beta-particle-emitting stent.

作者信息

Laird J R, Carter A J, Kufs W M, Hoopes T G, Farb A, Nott S H, Fischell R E, Fischell D R, Virmani R, Fischell T A

机构信息

Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.

出版信息

Circulation. 1996 Feb 1;93(3):529-36. doi: 10.1161/01.cir.93.3.529.

DOI:10.1161/01.cir.93.3.529
PMID:8565172
Abstract

BACKGROUND

Restenosis after successful percutaneous transluminal coronary angioplasty is the major factor limiting the long-term effectiveness of this procedure. Neointimal proliferation in response to arterial injury is an important contributor to restenosis. The use of radiation for the treatment of malignant and benign proliferative conditions has been well established. External beam irradiation and endovascular irradiation by use of an after-loading technique have been shown to inhibit neointimal proliferation in experimental models of restenosis. The objective of this study was to investigate whether low-dose irradiation from a beta-particle-emitting stent would inhibit neointimal proliferation after placement in porcine iliac arteries.

METHODS AND RESULTS

Fourteen titanium-mesh stents were implanted in the iliac arteries of nine NIH miniature swine. There were seven beta-particle-emitting radioisotope stents (32P, activity level 0.14 microCi) and seven control stents (31P, nonradioactive). Treatment effect was assessed by angiography and histomorphological examination of the stented iliac segments 28 days after implantation. There was a significant reduction in neointimal area (1.76 +/- 0.37 mm2 versus 2.81 +/- 1.22 mm2, P = .05) and percent area stenosis (24.6 +/- 2.9% versus 36.0 +/- 10.7%, P = .02) within the beta-particle-emitting stents compared with the control stents. Neointimal thickness, which was assessed at each wire site, was also significantly less within the treatment stents (0.26 +/- 0.04 mm versus 0.38 +/- 0.10 mm, P = .012). Scanning electron microscopy was performed on sections from four stents. This demonstrated endothelialization of both the treatment and control stents. There was no excess inflammatory reaction or fibrosis in the media, adventitia, or perivascular space of vessels treated with the beta-particle-emitting stent compared with control vessels. At 28 days, there was no difference in smooth muscle cell proliferation as measured by the proliferating cell nuclear antigen index.

CONCLUSIONS

A local, continuous source of low-dose endovascular irradiation via a beta-particle-emitting stent inhibits neointimal formation in porcine arteries. This low dose of local irradiation did not prevent endothelialization of the stents. This novel technique offers promise for the prevention of restenosis and warrants further investigation.

摘要

背景

经皮腔内冠状动脉成形术成功后的再狭窄是限制该手术长期疗效的主要因素。对动脉损伤产生的内膜增生是再狭窄的重要促成因素。放射疗法用于治疗恶性和良性增生性疾病已得到充分证实。在再狭窄的实验模型中,外照射和采用后装技术的血管内照射已显示出可抑制内膜增生。本研究的目的是调查β粒子发射支架的低剂量照射在植入猪髂动脉后是否会抑制内膜增生。

方法与结果

将14个钛网支架植入9只美国国立卫生研究院小型猪的髂动脉。其中有7个β粒子发射放射性同位素支架(32P,活度水平0.14微居里)和7个对照支架(31P,无放射性)。在植入后28天,通过血管造影和对植入支架的髂动脉节段进行组织形态学检查来评估治疗效果。与对照支架相比,β粒子发射支架内的内膜面积显著减小(1.76±0.37平方毫米对2.81±1.22平方毫米,P = 0.05),面积狭窄百分比也显著降低(24.6±2.9%对36.0±10.7%,P = 0.02)。在每个金属丝部位评估的内膜厚度在治疗支架内也显著更小(0.26±0.04毫米对0.38±0.10毫米,P =  0.012)。对4个支架的切片进行了扫描电子显微镜检查。这显示治疗支架和对照支架均有内皮化。与对照血管相比,用β粒子发射支架治疗的血管的中膜、外膜或血管周围间隙没有过度的炎症反应或纤维化。在28天时,通过增殖细胞核抗原指数测量的平滑肌细胞增殖没有差异。

结论

通过β粒子发射支架进行局部、持续的低剂量血管内照射可抑制猪动脉内膜形成。这种低剂量的局部照射并未阻止支架的内皮化。这项新技术为预防再狭窄带来了希望,值得进一步研究。