Tetramethylpyrazine-eluting stents prevented in-stent restenosis in a porcine model.
OBJECTIVE
Tetramethylpyrazine, a drug originally isolated from the rhizome 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 mm2 versus 1.29 +/- 1.02 mm2; P = 0.011) 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 +/- 2.5% 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.
Ma
Genshan
G
Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, China. magenshan@seu.edu.cn
Ding
Shu
S
Feng
Yi
Y
Shen
Chengxing
C
Chen
Lijuan
L
Chen
Zhong
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects; D006965:Hyperplasia / Q000473:pathology; D020366:Methylmethacrylate; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D011108:Polymers; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D020099:Coated Materials, Biocompatible; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D018809:Proliferating Cell Nuclear Antigen; D011719:Pyrazines; D020366:Methylmethacrylate; D011100:Polyglycolic Acid; C017953:tetramethylpyrazine