[Effects of controlled-release arsenic-trioxide-eluting stents on in-stent neointimal hyperplasia in coronary artery: experiment with dog model].
OBJECTIVE
To study the safety and efficacy of controlled-release arsenic-trioxide (As(2)O(3))-eluting stents to reduce in-stent neointimal hyperplasia in coronary artery.


METHODS
As(2)O(3) was sprayed onto the stainless steel coated with polybutyl methacrylate/nano-silica and poly-lactide-co-glycolide so as to make the controlled-release As(2)O(3)-eluting stents with the As(2)O(3) concentrations of 0, 1.6, 2.4, and 3.2 microg/mm(2). Thirty adult dogs were randomly divided into 5 equal groups to undergo deployment of bare stent, coated stent, and As(2)O(3)-eluting stent of low dose (1.6 microg/mm(2)), medium dose (2.4, microg/mm(2)), and high dose (3.2 microg/mm(2)) into the left anterior descending artery or circumflex coronary artery respectively, and aspirin 250 mg/day was given 3 days before operation until 4 weeks after operation. Four weeks after the operation the dogs underwent angiography and then killed. The coronary artery, heart, liver, spleen, lung, kidney, and brain were taken out for pathological examination.


RESULTS
The mean injury scores were similar in all groups. The values of mean neointimal thickness of the high-, medium-, and low-dose groups were (0.14 +/- 0.05) mm, (0.15 +/- 0.04) mm, and (0.27 +/- 0.03 mm) respectively, all significantly lower than those of the coated stent and bare stent groups [(0.39 +/- 0.06) mm and (0.33 +/- 0.02) mm respectively, all P < 0.01], with significant differences between the high and medium groups and low dose group (both P < 0.01). The neointimal areas of the high, medium, and low dose groups were (1.09 +/- 0.11) mm(2), (1.33 +/- 0.10) mm(2), and (1.93 +/- 0.29) mm(2) respectively, all significantly smaller than those of the coated stent and bare stent groups [(2.44 +/- 0.15) mm(2) and (2.40 +/- 0.32) mm(2), all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The stenosis rates of the high, medium, and low dose groups were (19.54 +/- 3.59)%, (22.18 +/- 3.3)%, and (36.22 +/- 5.17)% respectively, all significantly lower than those of the coated stent and bare stent groups [(50.39 +/- 3.03)%, and (46.88 +/- 5.85)% respectively, all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The luminal areas of the high, medium, and low dose groups were (5.14 +/- 0.55) mm(2), (4.97 +/- 0.38) mm(2), and (3.75 +/- 0.39) mm(2) respectively, all significantly larger than those of the coated stent and bare stent groups [(2.62 +/- 0.22) mm(2) and (3.10 +/- 0.66) mm(2) respectively, both P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). Pathological examination did not find intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, and inflammatory cell infiltration in all groups.


CONCLUSIONS
Capable of inhibiting neointimal hyperplasia in the coronary arteries dose-dependently after implantation, controlled-release As(2)O(3)-eluting stents is safe and applicable in treating coronary diseases.
Zhao
Jun-li
JL
Department of Cardiology, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, China.
Sun
Bao-gui
BG
Wen
Qin-zhu
QZ
Zhang
Jian-jun
JJ
Jin
Wei
W
Xue
Ji-xiang
JX
Zhuang
Wen-yan
WY
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D006965:Hyperplasia; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D011184:Postoperative Period; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide