Tetramethylpyrazine-eluting stents prevented in-stent restenosis in a porcine model

Objective: Tetramethylpyrazine, a drug originally isolated from the rbizorne of Ligusticum walliichi, is an inhibitor of phosphodiesterase and inhibits platelet aggregation and smooth muscle cell proliferation. The effect of the tetramethylpyrazine-eluting stent (TES) on preventing in-stent restenosis was investigated in comparison with control bare metal stents in a porcine coronary stent restenosis model. Methods: The TES was prepared by spray-coating the 2.5 to 3.0 mm X 15 to 20 mm bare metal stents with Tetramethylpyrazine monomer, methyl methacrylate copolymer, and polyglycolic acid. Stent overdilation injury (stent:artery = 1.1 to 1.2:1.0) was made with control bare stents (n = 5) and TES (n = 5) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) and histopathological assessments of stented coronary arteries were performed 4 weeks after stenting. Results: Quantitative coronary angiography showed the late lumen loss (0.28 +/- 0.08 mm versus 1.70 +/- 0.52 mm; P = 0.004) and percentage diameter stenosis (10.0 +/- 2.1% versus 60.2 +/- 23.5%; P = 0.01) were significantly lower in the TES group than that in the control group. Histopathological assessments of stented coronary arteries showed that the injury score and the in-stent area were similar between the groups (P > 0.05), whereas the lumen area was significantly larger (4.34 +/- 0.93 mm(2) versus 1.29 +/- 1.02 mm(2); p = 0.0 11) in the TES group than that in the control group. The number of proliferating cell nuclear antigen-positive cells was also significantly decreased in the TES group compared with the control group (14.7 +/- 12.5% versus 23.6 +/- 3.2%; P = 0.008). Moreover, apoptosis was enhanced in TES group while regrowth of endothelium was similar between the groups. Conclusions: TES inhibited the neointimal hyperplasia and reduced in-stent restenosis in a porcine coronary artery restenosis model.