Properties of China-made peripheral artery sirolimus-heparin eluting stent and its inhibition against in-stent restenosis

Objective To evaluate the physical properties, biocompatibility, and pharmacokinetics of the China-made sirolimus-heparin elnting stent (SHES) as well as its inhibition effect on the in-stent restenosis in vitro and in vivo. Methods Polylactide coglycotide (PLGA)-heparin complex was sprayed to the surface of sirolimus-coated nitinol stent to make the sirolimus-heparin eluting stent (SHES). The physical and degrading efficiency, blood compatibility, and pharmacokinetics of this stent were studied in vitro.Fifteen dogs were implanted with SHES + bare-metal stent (BMS) into the bilateral iliac arteries (n=4),sirolimus-eluting stentt (SES) + BMS into the bilateral iliac arteries (n=4), SHES+SES into the bilateral iliac arteries (n=4), and with 2 SHESs into the bilateral iliac arteries (n=2), and 2 SHESs into the abdominal aorta (n=1). Based on the condition of strict anticoagulation, 30, 60, and 240 days after the implantation angiography of the peripheral arteries where the stents were placed was performed in 7, 7, and 1 dog respectively. Then all of the dogs were killed. The compliance, radial force, and visibility of stentt,in-stent thrombosis, in-stent diameter, reference segment diameter, late loss of diameter, and restenosis rate were observed. Results The SHES had even surface coating, and good compliance and radial extension.Blood compatibility test showed only few platelets adhered to the stent surface without deformity or obvious aggregation, and the clotting time was prolonged because of the blood coagulation factors to be activated in a low level. Degrading test and pharmacokinetics in vitro showed that sirolimus could be continuously released in a period of 3 months and heparin in a period of 50 day. The whole 30 stents were successfully implanted into the dog peripheral arteries without complication. The SHES showed satisfactory compliance and good visibility , and its blood concentration of sirolimus was 1.79-2.22 ng/ml immediately after stent implantation, 0.4 ng/ml 7 d later, and its release could be continuous about 3 months. Angiography 30 days after the implantation showed no thrombosis and intimal hyperplasia. Angiography 60 days after the implantation showed 2 cases of SES obstruction due to in-stent thrombosis, 1 case of SHES stricture and 3 cases of BMS stricture resulted from intimal hyperplasia, and 1 case of mild sinking of the arterial lumen proximate to the SHES. There were significant differences in the in-stent diameter and its late loss value between the SHES, SES, and bare stent (F:0.049, P＜0.05 ; F: 0.047, P＜0.05 ). 240 days after the implantation two SHESs placed in bilateral iliac arteries of a dog were un-obstructed. Concluslon The China-made peripheral arterial SHES not only has good physical properties and biocompatibility, but also reduces the restenosis rate resulted thanks to its effective anticoagulation and the inhibitory effect on the intimal hyperplasia simultaneously. Key words: Stent;  Sirolimus;  Heparin;  Biocompatibile materials