Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1β-induced coronary artery in-stent restenosis in pigs.

Background: Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.

Methods: Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR).

Results: QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.

Conclusion: SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.