Endothelium-Dependent Vasomotor Dysfunction in Pig Coronary Arteries With Paclitaxel-Eluting Stents Is Associated With Inflammation and Oxidative Stress
Endothelium-Dependent Vasomotor Dysfunction in Pig Coronary Arteries With Paclitaxel-Eluting Stents Is Associated With Inflammation and Oxidative Stress
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DOI：
10.1016/j.jcin.2008.11.009
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发表时间：
2009-03-01
影响因子：
11.3
通讯作者：
Hou, Dongming
中科院分区：
文献类型：
--
作者：
Pendyala, Lakshmana K.;Li, Jinsheng;Hou, Dongming
目的评价重叠放置紫杉醇洗脱支架(PES)后冠状动脉心外膜和心肌内阻力、动脉血管运动功能、局部炎症反应和超氧阴离子(O-2(中心点))的产生。方法9只猪接受了重叠的冠状动脉内PES和裸金属支架(BMS)，3只假动物为幼稚动物。1个月后，通过组织病理学和扫描电子显微镜观察重叠区的炎症反应。采用血管造影术、器官腔张力法和荧光素发光法测定非支架冠脉参比节段的内皮血管舒缩功能和氧分压(中心点)，肌电图法测定远端阻力动脉的血管舒缩功能。结果紫杉醇洗脱支架术后晚期管腔丢失减少，但重叠节段的炎症反应和管腔炎症细胞黏附率高于骨髓支架(p<；0.001)。在无支架冠状动脉参考节段(近端和远端为15 mm)和灌注床阻力动脉(p<；0.05)处，PES患者对P物质的内皮依赖性松弛显著受损。相反，硝酸甘油和硝普钠对血管内皮非依赖性的松弛作用在两组之间是相似的。无支架冠脉近端和远端参考节段的局部O-2(中心点-)生成高于BMS和初始动脉的O-2(中心点-)生成(p<；0.001)。结论重叠的PES植入后，冠状动脉管道和阻力动脉均存在内皮依赖性的异常松弛。严重的局部炎症反应，以及局部氧化应激增强，可能导致血管运动功能障碍。(J Am Coll心脏ol Intv 2009；2：253-62)(C)美国心脏病学会基金会2009年
Objectives We sought to evaluate coronary epicardial and intramyocardial resistance, arterial vasomotor function, local inflammatory reaction, and superoxide anion (O-2(center dot-)) production after overlapping paclitaxel-eluting stent (PES) implantation in a porcine model.Background PES implantation has been shown to elicit coronary vasomotor dysfunction. However, underlying mechanisms remain largely unknown.Methods Nine pigs received overlapping PES and bare-metal stents (BMS) in the coronary arteries, and 3 sham animals were naive. At 1 month, inflammatory response at the overlapped region was assessed by histopathology and scanning electron microscopy. Endothelial vasomotor function and O-2(center dot-) at nonstented coronary reference segments were measured by angiography and organ chamber tensiometry, and lucigenin luminometry; vasomotor function of distal resistance arteries was measured by myography.Results Paclitaxel-eluting stents showed reduced late lumen loss, but inflammation and luminal inflammatory cell adherence were higher than for BMS (p < 0.001) at overlapped segments. Endothelium-dependent relaxation to substance P was significantly impaired in PES at nonstented coronary reference segments (>= 15 mm proximally and distally) and perfusion bed resistance arteries (p < 0.05). In contrast, endothelium-independent relaxation to nitroglycerin and sodium-nitroprusside was similar between groups. Local O-2(center dot-) production at both proximal and distal nonstented coronary reference segments was elevated for PES when compared with O-2(center dot-) production in BMS and naive arteries (p < 0.001).Conclusions Abnormal endothelium-dependent relaxation at both coronary conduit and resistance arteries was demonstrated after overlapping PES implantation. Profound localized inflammatory reaction, as well as enhanced local oxidative stress, may contribute to vasomotor dysfunction. (J Am Coll Cardiol Intv 2009;2:253-62) (C) 2009 by the American College of Cardiology Foundation