[Effects of control-releasing arsenic trioxide-eluting stent on intimal smooth muscle cells and type III collagen in canine coronary artery post-stent model].
OBJECTIVE
To study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model.


METHODS
Twenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis.


RESULTS
Subintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05).


CONCLUSIONS
Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.
Zhao
Jun-Li
JL
Department of Cardiology, the First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai. jlzhao2008cn@yahoo.com.cn
Sun
Bao-Gui
BG
Wen
Qin-Zhu
QZ
D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D024061:Collagen Type III / Q000378:metabolism*; D023903:Coronary Restenosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D054855:Drug-Eluting Stents; D005260:Female; D020007:Implants, Experimental; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D001152:Arsenicals; D024061:Collagen Type III; D010087:Oxides; D000077237:Arsenic Trioxide