高剂量率冠状动脉内放射治疗抑制猪支架置入和球囊损伤再狭窄模型中的内膜增生：血管造影、形态计量学和组织病理学分析

High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: angiographic, morphometric, and histopathologic analyses.

作者信息

Mazur W, Ali M N, Khan M M, Dabaghi S F, DeFelice C A, Paradis P, Butler E B, Wright A E, Fajardo L F, French B A, Raizner A E

机构信息

Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030, USA.

出版信息

Int J Radiat Oncol Biol Phys. 1996 Nov 1;36(4):777-88. doi: 10.1016/s0360-3016(96)00298-2.

DOI:10.1016/s0360-3016(96)00298-2

PMID:8960503

Abstract

PURPOSE

We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis.

METHODS AND MATERIALS

In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion.

RESULTS

The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control group, compared to -0.43 +/- 0.35 mm in the 15 Gy (p = 0.04) and -0.21 +/- 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 +/- 0.22 mm in the control group compared to -0.03 +/- 0.18 mm in the 10 Gy (p = 0.05) and 0.00 +/- 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 +/- 9% in the control group compared to 18 +/- 12% in the 15 Gy (p = 0.003) and 11 +/- 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 +/- 10% in the control groups, compared to 5 +/- 5% in the 15 Gy (p = 0.02) and 2 +/- 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments.

CONCLUSIONS

High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

摘要

目的

我们在猪冠状动脉再狭窄模型中，研究了高剂量率冠状动脉内照射对两种损伤（球囊过度扩张损伤和支架植入）后新生内膜增生的影响。

方法和材料

在34只汉福德小型猪中，每只猪的一段冠状动脉被选定用于损伤和治疗。动脉段分别接受192铱治疗，剂量为4分钟内10 Gy（8只动物）、6分钟内15 Gy（9只动物）、10分钟内25 Gy（9只动物）或对照（仅模拟钢丝；8只动物）。对治疗后的节段进行支架植入（左前降支和右冠状动脉）或球囊过度扩张（回旋支）损伤。28天后，进行重复冠状动脉造影并处死动物。以盲法进行定量冠状动脉造影、形态测量和广泛的组织病理学分析。

结果

在支架损伤的左前降支中，对照组从损伤后到处死时最小管腔直径的变化为-0.79±0.34（均值±标准差）mm，而15 Gy组为-0.43±0.35 mm（p = 0.04），25 Gy组为-0.21±0.50 mm（p = 0.01）；在球囊损伤的回旋支中，对照组为-0.31±0.22 mm，而10 Gy组为-0.03±0.18 mm（p = 0.05），15 Gy组为0.00±0.33（p = 0.01）。左前降支的狭窄面积百分比在对照组为36±9%，而15 Gy组为18±12%（p = 0.003），25 Gy组为11±11%（p < 0.001）；回旋支在对照组为16±10%，而15 Gy组为5±5%（p = 0.02），25 Gy组为2±2%（p = 0.009）。组织病理学显示，与对照血管相比，照射动脉中的新生内膜量显著减少。其他辐射效应包括间质纤维蛋白渗出、中膜变薄以及辐射动脉段的外膜纤维化和白细胞浸润。