Carter A J, Laird J R, Bailey L R, Hoopes T G, Farb A, Fischell D R, Fischell R E, Fischell T A, Virmani R
Walter Reed Army Institute of Research Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Circulation. 1996 Nov 15;94(10):2364-8. doi: 10.1161/01.cir.94.10.2364.
Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. The objective of this study was to evaluate the dose-related effects of a beta-particle-emitting radioactive stent in a porcine coronary restenosis model.
Thirty-seven swine underwent placement of 35 nonradioactive and 39 beta-particle-emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 microCi of 32P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0-microCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-microCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low-activity (0.15- and 0.5-microCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63 +/- 0.67 mm2 and high, 1.73 +/- 0.97 mm2 versus control, 2.40 +/- 0.87 mm2) and percent area stenosis (low, 26 +/- 7% and high, 26 +/- 12%) compared with control stents (37 +/- 12%, P < or = .01). The 1.0-microCi stents, however, had greater neointimal formation (4.67 +/- 1.50 mm2) and more luminal narrowing (64 +/- 16%) than the control stents (P < .0001).
The differential response to the doses of continuous beta-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.
冠状动脉内支架置入术后，新生内膜形成会导致再狭窄。经支架进行血管内放射治疗已显示可减少猪和兔髂动脉置入支架后的新生内膜形成。本研究的目的是评估在猪冠状动脉再狭窄模型中，发射β粒子的放射性支架的剂量相关效应。
37头猪接受了35个非放射性支架和39个发射β粒子的支架置入，这些支架的32P活度水平分别为23.0、14.0、6.0、3.0、1.0、0.5和0.15微居里。在支架置入28天后，通过组织学分析评估治疗效果。新生内膜和平滑肌细胞密度与支架活度增加呈负相关。高活度（3.0至23.0微居里）支架的新生内膜由纤维蛋白、红细胞、偶尔的炎性细胞和平滑肌细胞组成，管腔表面部分内皮化。在1.0微居里的支架中，新生内膜扩张，由平滑肌细胞和富含蛋白聚糖的基质组成。低活度（0.15和0.5微居里）支架的新生内膜由平滑肌细胞和基质组成，管腔表面完全内皮化。与对照支架相比，在低和高支架活度时，新生内膜面积（低活度为1.63±0.67平方毫米，高活度为1.73±0.97平方毫米，对照为2.40±0.87平方毫米）和面积狭窄百分比（低活度为26±7%，高活度为26±12%）均降低（对照为37±12%，P≤0.01）。然而，1.0微居里的支架比对照支架有更大的新生内膜形成（4.67±1.50平方毫米）和更严重的管腔狭窄（64±16%）（P<0.0001）。
在该实验模型中，对所用连续β粒子照射剂量的不同反应表明血管内放射与支架置入后血管修复之间存在复杂的生物学相互作用。需要进一步研究以确定该疗法预防支架再狭窄的临床潜力。
