Sheehy Alexander, Hsu Steve, Sinn Irene, Tai Julie, Kolodgie Frank D, Nakazawa Gaku, Yazdani Saami K, Quee Shawn Chin, Virmani Renu, Polyakov Igor
Abbott Vascular, 3200 Lakeside Dr. Santa Clara, CA 95054, USA.
Cardiovasc Revasc Med. 2011 Nov-Dec;12(6):375-84. doi: 10.1016/j.carrev.2011.05.003. Epub 2011 Jul 8.
The objective of this study was to investigate potential differences in vascular response to stenting of coronary arteries with bare metal (BMS) and drug-eluting (DES) stents in juvenile vs. mature swine.
Twenty-one mature (> 3 years) and 22 juvenile (6-9 months) Yucatan swine were implanted with 3 × 12-mm XIENCE V DES and ML VISION BMS in coronary arteries. After 7 and 28 days, vessels were analyzed using light microscopy (n = 5-7) and confocal and scanning electron microscopy (n = 5-10). Messenger RNA expression levels of inflammatory and endothelial gene markers were tested from stented tissue at 7 and 28 days (n = 3). A 2 × 2 analysis of variance followed by t tests compared treatment and/or age effects.
No age differences in neointimal area and percentage stenosis were measured. Juvenile swine exhibited increased fibrin scores compared to mature swine (2.6 ± 0.5 vs. 2.2 ± 0.5, P < .05) at 7 days, with no age-related difference at 28 days. At 7 days, significant increases in para-strut inflammation (P < .01) and in VCAM-1, ICAM-1, CD40 and MCP-1 gene expression (P < .05) were observed in mature swine, but differences were largely resolved by 28 days. DES exhibited less endothelial coverage than BMS at 7 days, but this difference was abrogated by 28 days, with no difference between age groups.
Our results indicate that mature swine exhibited an increased foreign body response compared to mature swine at 7 and 28 days following stenting that may indicate marginal delays in resolution of foreign body response in aged populations. These differences are unlikely to affect methodologies for preclinical stent safety evaluations.
本研究的目的是调查幼年与成年猪在接受裸金属支架（BMS）和药物洗脱支架（DES）冠状动脉支架植入术后血管反应的潜在差异。
将21只成年（>3岁）和22只幼年（6 - 9个月）的尤卡坦猪的冠状动脉植入3×12毫米XIENCE V DES和ML VISION BMS。7天和28天后，使用光学显微镜（n = 5 - 7）以及共聚焦和扫描电子显微镜（n = 5 - 10）对血管进行分析。在7天和28天时从支架植入组织中检测炎症和内皮基因标志物的信使核糖核酸表达水平（n = 3）。采用2×2方差分析，随后进行t检验以比较治疗和/或年龄效应。
未测量到新生内膜面积和狭窄百分比的年龄差异。幼年猪在7天时与成年猪相比纤维蛋白评分增加（2.6±0.5对2.2±0.5，P <.05），28天时无年龄相关差异。在7天时，成年猪观察到支架旁炎症显著增加（P <.01）以及VCAM - 1、ICAM - 1、CD40和MCP - 1基因表达显著增加（P <.05），但到28天时这些差异基本消失。DES在7天时内皮覆盖比BMS少，但到28天时这种差异消失，各年龄组之间无差异。
我们的结果表明，成年猪在支架植入后7天和28天时与幼年猪相比表现出更强的异物反应，这可能表明老年人群异物反应消退存在轻微延迟。这些差异不太可能影响临床前支架安全性评估的方法。
