Farb A, Tang A L, Shroff S, Sweet W, Virmani R
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):889-98. doi: 10.1016/s0360-3016(00)00661-1.
Studies have shown a potential benefit of brachytherapy in preventing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to explore the histologic changes following placement of beta-emitting radioactive stents in arteries focusing on intimal responses and endothelialization.
3.0-mm beta-emitting (32)P stents (6-microCi and 24-microCi) were placed in rabbit iliac arteries with nonradioactive stents serving as controls. Animals were euthanized at 3 months and histologic assessment, morphometry, and analysis of endothelialization were performed.
The lumen areas of 24-microCi stents (4.24 +/- 0.22 mm(2), p < 0.0007) and 6-microCi stents (4.23 +/- 0.49 mm(2), p < 0.01) were larger than control stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11. 4 +/- 3.0% in the 24-microCi stents (p < 0.007 vs. 6-microCi stents and p < 0.0001 vs. control stents), 18.7 +/- 6.4% in the 6-microCi stents (p < 0.02 vs. control stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-microCi stent (54.2% smaller than controls and 42.7% smaller than 6-microCi); the neointimal area of the 6-microCi stents was 20.0% less than controls. The control stent neointima consisted of smooth muscle cells in a proteoglycan and collagen matrix. In contrast, the intima of radioactive stents showed persistent fibrin thrombus with nonconfluent areas of matrix. Actin-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicator of increased endothelial permeability, was present on 86 +/- 9% of the stented segment of 6-microCi stents vs. 10 +/- 11% in controls (p < 0.0001). Scanning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6-microCi stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized.
(32)P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studies with complete arterial healing are needed to determine whether there is sustained neointimal inhibition by stent-delivered brachytherapy.
研究表明近距离放射疗法在预防再狭窄方面具有潜在益处。然而，血管内放射对动脉愈合的影响尚未完全明确。本研究的目的是探讨在动脉中植入发射β射线的放射性支架后的组织学变化，重点关注内膜反应和内皮化。
将3.0毫米发射β射线（³²P）的支架（6微居里和24微居里）植入兔髂动脉，以非放射性支架作为对照。在3个月时对动物实施安乐死，并进行组织学评估、形态测量和内皮化分析。
24微居里支架的管腔面积（4.24±0.22平方毫米，p<0.0007）和6微居里支架的管腔面积（4.23±0.49平方毫米，p<0.01）大于对照支架（3.64±0.44平方毫米）。24微居里支架的平均管腔狭窄百分比为11.4±3.0%（与6微居里支架相比p<0.007，与对照支架相比p<0.0001），6微居里支架为18.7±6.4%（与对照支架相比p<0.02），对照支架为25.0±4.9%。24微居里支架的新生内膜面积最小（比对照小54.2%，比6微居里支架小42.7%）；6微居里支架的新生内膜面积比对照小20.0%。对照支架的新生内膜由蛋白聚糖和胶原基质中的平滑肌细胞组成。相比之下，放射性支架的内膜显示有持续的纤维蛋白血栓，基质区域不连续。放射性支架植入后，肌动蛋白阳性内膜细胞密度降低，但内膜细胞增殖增加。伊文思蓝染色显示6微居里支架植入段有86±9%存在内皮通透性增加，而对照支架为10±11%（p<0.0001）。扫描电子显微镜显示对照支架内膜表面97±8%实现了内皮化；相比之下，6微居里支架的中部仍未内皮化，整个支架表面只有33±15%（p<0.0001）实现了内皮化。
³²P发射β射线的支架可减少新生内膜生长，但在3个月时愈合不完全，内皮化较差。需要进行更长时间的完整动脉愈合研究，以确定支架递送的近距离放射疗法是否能持续抑制新生内膜。
