Prunotto M, Vignolini C, Lolli V, Black A, Gaggianesi S, Santarelli A, Galloni M
Veterinary Morphophysiology Department, University of Turin, Italy - via Leonardo da Vinci 144, Grugliasco, Italy.
J Biomed Mater Res A. 2009 Mar 15;88(4):872-9. doi: 10.1002/jbm.a.31940.
Stent-based delivery of tacrolimus has shown neointimal hyperplasia and restenosis reduction; FK506 is a water insoluble macrolide immunosuppressant. The purpose of this study was to evaluate acute and chronic tissue response to a polymer-free FK506 drug-eluting stent implantation in a porcine coronary artery model. Seventy-eight nonatherosclerotic minipigs underwent successful placement of 134 stents (control n = 56; FK506 (1.5 microg/mm(2)) n = 44; FK506 (2.6 microg/mm(2)) n = 34) at 7, 15, 30, 90, or 180 days. Endothelialisation was almost complete at 7 days, complete at 15 days. At 30 and 90 days, mean neointimal thickness, neointimal area, and % stenosis was significantly less for drug-eluting stents compared with controls. At 180 days, histomorphometric values were similar for eluting and control stents. The FK506-eluting stent allows for a complete re-endothelialisation at 15 days and favorably moderate neointimal hyperplasia at 30 and 90 days in the porcine coronary model. Because of a possible limited bioavailability of FK506, long-term inhibition of neointimal formation was not sustained at the considered follow-up.
基于支架的他克莫司递送已显示出可减少内膜增生和再狭窄；FK506是一种水不溶性大环内酯类免疫抑制剂。本研究的目的是评估在猪冠状动脉模型中植入无聚合物的FK506药物洗脱支架后的急性和慢性组织反应。78只非动脉粥样硬化小型猪在第7、15、30、90或180天成功植入了134个支架（对照组n = 56；FK506（1.5微克/平方毫米）n = 44；FK506（2.6微克/平方毫米）n = 34）。内皮化在7天时几乎完成，在15天时完全完成。在30天和90天时，与对照组相比，药物洗脱支架的平均内膜厚度、内膜面积和狭窄百分比显著更低。在180天时，洗脱支架和对照支架的组织形态计量学值相似。在猪冠状动脉模型中，FK506洗脱支架在15天时可实现完全再内皮化，并在30天和90天时有利于适度抑制内膜增生。由于FK506的生物利用度可能有限，在考虑的随访期内，对内膜形成的长期抑制未能持续。
