Experimental Study Of Tetramethylpyrazine- Eluting Stent To Prevent In-Stent Restenosis In A Porcine Model

Objective: To develop an experimental porcine restenosis model of coronary artery, and to evaluate the short-term effect of Tetramethylpyrazine-eluting stent to prevent in-stent restenosis.Methods: Bare metal stents were uniformly sprayed painting with Tetramethylpyrazine monomer(200μg),methyl methacrylate copolymer and polyglycolic acid,and prepared Tetramethylpyrazine-eluting stents.Fourteen healthy mini-swines were choosed, and a bare metal stent or Tetramethylpyrazine-eluting stent(TES) was randomly implanted into LAD in each swine (stent/vessel=1.1-1.2/1.0) by coronary angiography. No stent malapposition,local artery dissection,aneurysm,hematoma in vessel wall,angiorrhexis and major fresh thrombogenesis formed by IVUS.QCA and IVUS were detected 28 days later, then swines were sacrificed and the in-stent restenosis were measured by histomorphology and PCNA index.Results: Stents were implanted into LADs of fourteen swines successfully, but four swines were dead within two hours after stenting. Five BMSs(the control group) and five TESs were implanted respectively in ten swines which survived and re-examinations were completed 28 day later.QCA showed the follow-up vessel diameter was diminished markedly compared with the post-stenting vessel diameter in both groups(P<0.01), and the late lumen loss in the TES group was lower compared with the control group(0.28±0.08mm vs 1.70±0.52mm, P=0.004), the percentage of diameter stenosis was significantly decreased (10.0±2.1% vs 60.2±23.5%, P=0.01).The in-stent restenosis rate was 60% in the control group, compared with 0 in the TES group.IVUS analysis showed the average percent area of stenosis was significantly reduced by 73% in the TES group compared with the control group(19.1±10.5% vs 71.0±23.3%, P=0.007). Histomorphometry of the TES group compared with the control group showed that the injury score and the in-stent area were similar(P>0.05),but the lumen area was increased visibly (4.34±0.93mm2 vs 1.29±1.02mm2, P=0.011), the neointimal area was decreased markedly (1.51±0.45mm2 vs 4.60±1.39mm2, P=0.004), resulting in a 67% reduction of the average percent area of stenosis(25.6±5.0 % vs 77.9±19.7%, P=0.003). As compared with 23.6±3.2% in the control group,the PCNA index was reduced to 14.7±2.5% in the TES group(P=0.008). The in-stent area,lumen area,neointimal area and average percent area of stenosis were similar by IVUS analysis in comparison to histomorphometric results in both groups(P>0.05).