Impact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis
Impact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis
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DOI：
10.1016/j.jcin.2015.03.020
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发表时间：
2015-07-01
影响因子：
11.3
通讯作者：
Granada, Juan F.
中科院分区：
文献类型：
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作者：
Gongora, Carlos A.;Shibuya, Masahiko;Granada, Juan F.
目的：本研究旨在比较紫杉醇包被球囊（PCB）浓度对组织水平和血管愈合的影响，采用3种不同的PCB技术(In。Pact Pacific = 3 μ g/mm(2), Lutonix = 2 μ g/mm(2), Ranger = 2 μ g/mm(2)。背景：使用多氯联苯的最佳治疗剂量尚未确定。方法在PCB充气后60天内测量紫杉醇组织水平（Ranger和In）。在健康猪的股浅动脉（18头猪，36条血管）。采用家族性高胆固醇血症猪股浅动脉支架内再狭窄模型（6头猪，24根血管）进行疗效研究。裸金属支架植入两周后，每个支架内再狭窄部位随机使用PCB或未涂覆的对照球囊（Sterling）。PCB治疗28天后进行定量血管分析和组织学评价。结果所有PCB技术在球囊充气后4小时显示相当的紫杉醇组织水平。28天时，所有PCB均达到治疗组织水平；然而，In。在所有时间点，Pact多氯联苯导致的组织浓度高于其他多氯联苯组。与对照组相比，所有PCB组的组织学新生内膜抑制都有所下降，其中in的下降幅度更大。协议组。然而，在2 μ g/mm(2) PCB组中，新生内膜更成熟，并且含有较少的支架周围纤维蛋白沉积。结论：与临床确定的多氯联苯剂量相比，低剂量多氯联苯技术的长期组织水平较低，但新内膜抑制程度相当，纤维蛋白沉积较少。这些发现对减少再狭窄和临床结果的影响有待进一步研究。(C) 2015年由美国心脏病学会基金会发布。
OBJECTIVES This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In. Pact Pacific = 3 mu g/mm(2), Lutonix = 2 mu g/mm(2) and Ranger = 2 mu g/mm(2)) in the experimental setting.BACKGROUND The optimal therapeutic dose for PCB use has not been determined yet.METHODS Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In. Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment.RESULTS All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In. Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In. Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-mu g/mm(2) PCB groups.CONCLUSIONS Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated. (C) 2015 by the American College of Cardiology Foundation.