Wilson Gregory J, Polovick Jason E, Huibregtse Barbara A, Poff Bradley C
Department of Laboratory Medicine and Pathobiology, University of Toronto, Hospital for Sick Children, Ontario, Canada.
Cardiovasc Res. 2007 Nov 1;76(2):361-72. doi: 10.1016/j.cardiores.2007.07.004. Epub 2007 Jul 18.
At 4-year follow-up, paclitaxel-eluting stents (PES, TAXUS) have demonstrated clinical effectiveness in reducing restenosis without increasing death or myocardial infarction. Concerns remain with all drug-eluting stents, however, regarding potential interference with long-term healing, particularly in zones with adjacent stent overlap due to theoretical doubling in both drug release and tissue contact with coating polymer. Therefore, we evaluated long-term healing of overlapped TAXUS stents in an accepted animal model.
Seventy-one non-injured swine underwent coronary artery placement of 138 overlapping stent-pairs (91 PES TAXUS Liberté 1 microg/mm(2) slow release formulation, 3.0 or 3.5 mm diameter pairs and 47 control bare metal Liberté pairs) deployed at a 1.1:1 to 1.2:1 target stent-to-artery diameter ratio. Pathological analysis was performed at 30 (9 bare, 10 paclitaxel), 90 (9 bare, 10 paclitaxel), 180 (10 bare, 16 paclitaxel), 360 (10 bare, 21 paclitaxel), and 580 (9 bare, 22 paclitaxel) days.
At all time intervals overlapped TAXUS stents were consistently endothelialized and free of luminal thrombus or vascular dilatation. Full healing, however, was delayed compared to control, with macrophage processed para-strut fibrin and cellular debris still present, but reduced and sequestered from blood flow by an endothelialized neointima at 360 and 580 days. While neointimal thickness in TAXUS overlap zones was significantly less than control at 30 days, greater neointima formation was observed with TAXUS at > or =90 days, but was stable and did not progress further from 90 to 580 days.
In this porcine model TAXUS stents demonstrated safety and acceptable healing with prolonged time to resolution of para-strut deposits, and did not produce the sustained neointimal suppression seen clinically.
在4年的随访中，紫杉醇洗脱支架（PES，TAXUS）已证明在降低再狭窄方面具有临床有效性，且未增加死亡或心肌梗死的发生率。然而，所有药物洗脱支架都存在一个问题，即可能会干扰长期愈合，特别是在支架相邻重叠区域，因为理论上药物释放和组织与涂层聚合物的接触都会加倍。因此，我们在一个公认的动物模型中评估了重叠TAXUS支架的长期愈合情况。
71只未受伤的猪接受了冠状动脉内138对重叠支架的植入（91对PES TAXUS Liberté 1微克/毫米²缓释制剂，直径为3.0或3.5毫米的支架对，以及47对对照裸金属Liberté支架对），目标支架与动脉直径比为1.1:1至1.2:1。在30天（9个裸支架，10个紫杉醇支架）、90天（9个裸支架，10个紫杉醇支架）、180天（10个裸支架，16个紫杉醇支架）、360天（10个裸支架，21个紫杉醇支架）和580天（9个裸支架，22个紫杉醇支架）进行病理分析。
在所有时间间隔内，重叠的TAXUS支架均持续内皮化，无管腔内血栓或血管扩张。然而，与对照组相比，完全愈合有所延迟，巨噬细胞处理后的支架旁纤维蛋白和细胞碎片仍然存在，但在360天和580天时，这些物质被内皮化的新生内膜减少并与血流隔离。虽然TAXUS重叠区域的新生内膜厚度在30天时明显小于对照组，但在≥90天时观察到TAXUS组有更多的新生内膜形成，但从90天到580天新生内膜稳定且未进一步进展。
在这个猪模型中，TAXUS支架显示出安全性和可接受的愈合情况，支架旁沉积物的消退时间延长，且未产生临床上所见的持续性新生内膜抑制。
