Salu Koen J, Huang Yanming, Bosmans Johan M, Liu Xiaoshun, Li Shengqiao, Wang Lan, Verbeken Eric, Bult Hidde, Vrints Chris J, De Scheerder Ivan K
Division of Cardiology, University of Antwerp, Wilrijk, Belgium.
Coron Artery Dis. 2003 Dec;14(8):545-55. doi: 10.1097/00019501-200312000-00005.
Polymer-based, drug-eluting stents, are currently under extensive investigation in the conquest against in-stent restenosis. Concern remains, however, about potential long-term lack of biocompatibility of the polymers used in these studies. Therefore, this study aimed to evaluate in porcine coronary arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid oil stent-coating and (2) the efficacy of this coating in preventing in-stent restenosis when cytochalasin D--an inhibitor of actin filament formation, that interferes with cell proliferation and migration--was added.
To assess in vivo biocompatibility of the oil coating, 15 bare and 15 oil-coated stents were randomly deployed in coronary arteries of 15 pigs. No difference in tissue response, regarding inflammation or proliferation, was seen between both groups at five days or at four weeks follow-up. To evaluate the efficacy of the coating in preventing in-stent restenosis by adding a potential anti-restenotic drug, stents were dip-coated in 20 mg cytochalasin D/ml oil solution, resulting in 93 +/- 18 microg cytochalasin D/stent load (n = 3). In vitro drug release studies showed sustained release up to four weeks. Next, 11 oil-coated and 11 cytochalasin D-loaded stents were randomly implanted in coronary arteries of 11 pigs. At four weeks, a 39% decrease in neointimal hyperplasia (p < 0.05, ANCOVA, with injury as covariate) was found in cytochalasin D-loaded stents compared to oil-coated stents.
This new natural oil stent-coating shows excellent biocompatibility to vascular tissue. Local cytochalasin D delivery from this stent-platform significantly inhibits neointimal hyperplasia in a porcine coronary model.
基于聚合物的药物洗脱支架目前正在针对支架内再狭窄的攻克方面进行广泛研究。然而，对于这些研究中所使用聚合物潜在的长期生物相容性问题，人们仍存担忧。因此，本研究旨在评估一种新型天然二十碳五烯酸油支架涂层在猪冠状动脉中的（1）体内生物相容性，以及（2）当添加细胞松弛素D（一种肌动蛋白丝形成抑制剂，可干扰细胞增殖和迁移）时该涂层预防支架内再狭窄的效果。
为评估油涂层的体内生物相容性，将15个裸支架和15个油涂层支架随机植入15头猪的冠状动脉中。在五天或四周随访时，两组在组织反应（炎症或增殖方面）上未见差异。为通过添加一种潜在的抗再狭窄药物来评估涂层预防支架内再狭窄的效果，将支架浸涂于20mg细胞松弛素D/ ml油溶液中，每个支架的负载量为93±18μg细胞松弛素D（n = 3）。体外药物释放研究显示可持续释放长达四周。接下来，将11个油涂层支架和11个负载细胞松弛素D的支架随机植入11头猪的冠状动脉中。四周时，与油涂层支架相比，负载细胞松弛素D的支架内膜增生减少了39%（p < 0.05，协方差分析，以损伤作为协变量）。
这种新型天然油支架涂层对血管组织显示出优异的生物相容性。从该支架平台局部递送细胞松弛素D可显著抑制猪冠状动脉模型中的内膜增生。
