In-stent restenosis limitation with stent-based controlled-release nitric oxide: Initial results in rabbits

In-stent restenosis limitation with stent-based controlled-release nitric oxide: Initial results in rabbits
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DOI:
10.1148/radiol.2302020417
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发表时间:
2004-02-01
期刊:
影响因子:
19.7
通讯作者:
Dake, MD
Dake, MD
中科院分区:
医学1区
文献类型:
--
作者:
Do, YS;Kao, EY;Dake, MD

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目的:评价支架内NO供体控释对兔支架内再狭窄的抑制作用。材料与方法:制备含NO供体或可生物降解聚合物(聚乳酸-乙交酯-聚乙二醇)的生物可吸收微球,并将其植入支架内。体外测定含NO微球每天的NO释放量。新西兰大白兔(n=8)的主动脉内植入无微球支架和含聚合物(对照)微球支架。分别于术后7天(n=5)和28天(n=3)取材,测定环鸟苷(CGMP)水平(7天)、增殖细胞核抗原阳性细胞数(7天)和内膜/中膜比率(7天和28天),采用单因素方差分析进行统计学处理。结果:含NO微球在第1周首次给药后释放NO,随后持续释放3周。与对照组相比,未处理组的cGMP水平在第7天显著升高,增殖细胞核抗原阳性细胞显著减少(P<0.05)。术后7天和28天,未治疗组内膜-中膜比对照组分别减少46%和32%(平均0.14+/-0:01[标准差]vs0,26+/-0.02,28天1.34+/-0.05vs1.98+/-0.08)。结论:支架内NO供体控释显著减少支架内再狭窄,并与血管cGMP增加和增殖抑制有关。((C))RSNA,2003年。
PURPOSE: To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits.MATERIALS AND METHODS: Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance.RESULTS: NO-containing microspheres released NO with an initial bolus in the 1 st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated relative to controls (P < .05). Intima-to-group media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days; respectively (mean, 0.14 +/- 0:01 [standard error] vs 0,26 +/- 0.02 at 7 days P < .01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days P < .01).CONCLUSION: Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation. ((C))RSNA, 2003.