Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Circ Cardiovasc Interv. 2011 Oct 1;4(5):438-46. doi: 10.1161/CIRCINTERVENTIONS.110.959957. Epub 2011 Oct 4.
Animal models used to gain insight into the vascular response to drug-eluting stents are generally juvenile and nonatherosclerotic, whereas stents are placed in patients with complex atherosclerosis and comorbidities. Hence, models reflecting these complexities are needed to help elucidate the vascular effects of drug-eluting stents. We compared the vascular responses with bare metal stent (BMS) and paclitaxel-eluting stent (PES) implantation in a diabetic/hypercholesterolemic (DM/HC) porcine model of advanced coronary atherosclerosis with the standard juvenile porcine model.
Two studies using similar stent procedural protocols were performed in either DM/HC (n=20) or domestic swine (non-DM/HC, n=20). Animals pretreated with dual-antiplatelet therapy, underwent BMS or PES implantation (1/artery, 2 stents per animal) and were euthanized 30 or 90 days later. DM/HC resulted in a 24% increase in platelet aggregation (P=0.05 versus baseline), whereas dual-antiplatelet therapy reduced platelet aggregation in both groups (P<0.0001). DM/HC pigs developed substantially greater neointimal area versus non-DM/HC pigs, regardless of stent type, (P=0.004 for BMS at 30 days and P=0.002 at 90 days, P=0.005 for PES at 30 days, P=0.002 at 90 days). Compared with non-DM/HC pigs, reendothelialization was delayed in DM/HC pigs, more so after PES implantation. Increased para-strut leukocytes were observed for PES compared with BMS in the DM/HC pigs at both 30 days (P=0.023) and 90 days (P=0.04). As well, increased T-lymphocyte infiltration was seen in the DM/HC pigs.
Stent implantation in a DM/HC swine model provides a metabolic environment closer to human disease, including hyperglycemia, hypercholesterolemia, and increased platelet aggregation. This model augmented differences in the vascular response between PES and BMS that are not as clearly evident in the non-DM/HC swine, including increased neointimal area, delayed reendothelialization, and greater, persistent vascular inflammation.
用于深入了解药物洗脱支架血管反应的动物模型通常是幼年且非动脉粥样硬化的，而支架则放置在患有复杂动脉粥样硬化和合并症的患者中。因此，需要反映这些复杂性的模型来帮助阐明药物洗脱支架的血管效应。我们比较了在糖尿病/高胆固醇血症（DM/HC）的晚期冠状动脉粥样硬化猪模型与标准幼年猪模型中，裸金属支架（BMS）和紫杉醇洗脱支架（PES）植入的血管反应。
在 DM/HC（n=20）或国内猪（非 DM/HC，n=20）中进行了两项使用类似支架手术方案的研究。接受双联抗血小板治疗的动物接受 BMS 或 PES 植入（1/动脉，每只动物 2 个支架），并在 30 或 90 天后安乐死。DM/HC 导致血小板聚集增加 24%（P=0.05 与基线相比），而双联抗血小板治疗降低了两组的血小板聚集（P<0.0001）。无论支架类型如何，DM/HC 猪的新生内膜面积都明显大于非 DM/HC 猪（BMS 在 30 天时为 P=0.004，90 天时为 P=0.002，PES 在 30 天时为 P=0.005，90 天时为 P=0.002）。与非 DM/HC 猪相比，DM/HC 猪的再内皮化延迟，PES 植入后更为明显。与 BMS 相比，在 DM/HC 猪中，在 30 天（P=0.023）和 90 天（P=0.04）时，PES 观察到支架旁白细胞增多。此外，在 DM/HC 猪中观察到 T 淋巴细胞浸润增加。
在 DM/HC 猪模型中植入支架提供了更接近人类疾病的代谢环境，包括高血糖、高胆固醇血症和血小板聚集增加。与非 DM/HC 猪相比，这种模型增强了 PES 和 BMS 之间血管反应的差异，这些差异在非 DM/HC 猪中并不明显，包括新生内膜面积增加、再内皮化延迟以及更大、持续的血管炎症。
