Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation - Inhibition through reduction of inflammation?
Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation - Inhibition through reduction of inflammation?
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DOI：
10.1161/01.cir.0000066914.95878.6d
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发表时间：
2003-06-03
期刊：
影响因子：
37.8
通讯作者：
Krams, R
中科院分区：
文献类型：
--
作者：
Carlier, SG;van Damme, LCA;Krams, R
背景-低壁切应力（WSS）增加静脉移植物和支架中的新生内膜增生（NH）.我们研究了WSS和NH形成支架的因果关系，通过局部增加WSS与分流器（抗再狭窄扩散器，Endoart SA）放置在stent.Methods和结果的中心-在9只兔子喂高胆固醇饮食2个月，诱导内皮功能障碍，18支架植入在右和左髂外动脉（1支架每血管）。在植入前后和4周随访时通过定量血管造影测量管腔直径，此时确定巨噬细胞积聚和内弹性膜中断。分析了ARED内（S + ARED）、ARED外（S[-] ARED）和对侧对照支架（SCTRL）相应节段中支架节段的横截面。通过计算流体动力学推导出由ARED放置引起的WSS变化。计算流体动力学分析表明，WSS从0.38增加到0.82 N/m（2），在S + ARED放置后立即。这种剪应力的增加伴随着（1）定量血管造影显示的较低的平均晚期管腔丢失（[减去] 0.23 +/- 0.22对比[减去] 0.58 +/- 0.30 mm，P = 0.02），（2）NH减少（1.48 +/- 0.58、2.46 +/- 1.25和2.36 +/- 1.13 mm（2），P < 0.01，分别为S + ARED、S[-] ARED和SCTRL），（3）炎症评分和损伤评分降低。剪切应力的增加并没有改变损伤评分和NH或炎症评分和NH.Conclusions之间的关系-新开发的ARED分流显着增加WSS，并在WSS的这种局部增量是伴随着局部减少NH和局部减少炎症和损伤。因此，本研究是第一个提供直接证据的一个重要的调节作用，支架内新生内膜增生的剪切应力。
Background - Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent.Methods and Results - In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries ( 1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S + ARED), outside the ARED (S[minus] ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m(2) in the S + ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus] 0.23 +/- 0.22 versus [minus] 0.58 +/- 0.30 mm, P = 0.02), (2) reduction in NH (1.48 +/- 0.58, 2.46 +/- 1.25, and 2.36 +/- 1.13 mm(2), P < 0.01, respectively, for S + ARED, S[minus] ARED, and SCTRL), and ( 3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH.Conclusions - The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.