Thrombogenicity and Early Vascular Healing Response in Metallic Biodegradable Polymer-Based and Fully Bioabsorbable Drug-Eluting Stents

Thrombogenicity and Early Vascular Healing Response in Metallic Biodegradable Polymer-Based and Fully Bioabsorbable Drug-Eluting Stents
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DOI:
10.1161/circinterventions.115.002427
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发表时间:
2015-06-01
影响因子:
5.6
通讯作者:
Joner, Michael
Joner, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Koppara, Tobias;Cheng, Qi;Joner, Michael

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背景-急性血栓形成和再内皮化代表了与冠状动脉支架安全性相关的临床相关终点,迄今为止尚未在可生物降解聚合物基药物洗脱金属支架和完全生物可吸收支架之间进行比较。方法和结果-我们研究了细支柱可生物降解聚合物金属依维莫司洗脱支架(EES)、厚支柱完全可生物降解支架之间急性血栓形成和再内皮化的比较结果生物可吸收EES、厚支柱可生物降解聚合物金属生物莫司洗脱支架和对照裸金属支架。离体猪动静脉分流模型用于评估血小板聚集,而健康兔髂股支架植入模型用于评估再内皮化和炎症。使用共聚焦显微镜检测针对CD61/CD42b的荧光标记抗体染色,以鉴定聚集的血小板,CD14/PM-1和RAM-11,以鉴定中性粒细胞和单核细胞/巨噬细胞。通过扫描电子显微镜评估内皮恢复,而 CD31/PECAM-1 用于确认内皮成熟度。与生物可吸收 EES 和生物莫司洗脱支架相比,EES 的急性血栓形成性明显降低。与可生物吸收的 EES 相比,EES 在 28 天时显示出更大的再内皮化作用,并在 14 天时显示出单核细胞/巨噬细胞的炎症细胞粘附减少。只有裸金属支架在 28 天时表现出完全的再内皮化。结论 - 这些结果表明临床实践中使用的当代支架在血栓形成和血管愈合方面存在差异趋势,并表明需要对生物可吸收 EES 进行长期辅助抗血栓药物治疗。
Background-Acute thrombogenicity and re-endothelialization represent clinically relevant end points pertaining to the safety of coronary stents, which have not been compared among biodegradable polymer-based drug-eluting metallic stents and fully bioabsorbable scaffolds to date.Methods and Results-We investigated comparative outcomes with respect to acute thrombogenicity and re-endothelialization among thin-strut biodegradable polymer metallic everolimus eluting stents (EES), thick-strut fully bioabsorbable EES, thick-strut biodegradable polymer metallic biolimus-eluting stents and control bare metal stents. An ex-vivo porcine arterio-venous shunt model was used to assess platelet aggregation, whereas a healthy rabbit model of iliofemoral stent implantation was used to assess re-endothelialization and inflammation. Confocal microscopy was used to detect fluorescently labeled antibody staining directed against CD61/CD42b for the identification of aggregated thrombocytes, CD14/PM-1, and RAM-11 for identification of neutrophils and monocytes/macrophages. Endothelial recovery was assessed by scanning electron microscopy, whereas CD31/PECAM-1 was used to confirm endothelial maturity. EES demonstrated significantly less acute thrombogenicity compared with bioabsorbable EES and biolimus-eluting stents. EES showed greater re-endothelialization at 28 days and reduced inflammatory cell adhesion of monocytes/macrophages at 14 days compared with bioabsorbable EES. Only bare metal stents showed complete re-endothelialization at 28 days.Conclusions-These outcomes indicate differential trends in thrombogenicity and vascular healing among contemporary stents used in clinical practice and suggest a need for long-term adjunct antithrombotic pharmacotherapy for bioabsorbable EES.