Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, 8 Corporate Drive, Orangeburg, NY, USA.
Circ Cardiovasc Interv. 2011 Oct 1;4(5):447-55. doi: 10.1161/CIRCINTERVENTIONS.110.960260. Epub 2011 Sep 27.
Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.
A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm(2), n=16), low-dose (300 μg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups.
The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.
药物涂层球囊在治疗外周血管疾病的介入治疗中迅速成为一种治疗选择。本研究的目的是验证这样一种假设，即在家族性高胆固醇血症猪的新型基于损伤的股浅动脉模型中，用 mTOR 抑制剂依维莫司（ZCB）涂层的血管成形球囊可抑制新生内膜增生。
共纳入 44 头家族性高胆固醇血症猪（12 头用于研究组织药代动力学，32 头用于研究安全性和疗效）。所有股浅动脉段均行 Fogarty 球囊剥脱术，继之行球囊血管成形术。在药代动力学研究中，共使用了 24 个 ZCB（300 μg/cm(2)）。在 ZCB 充气后 5 分钟（组织 162 ng/mg）、24 小时（组织 5.9 ng/mg）和 28 天（组织 0.007 ng/mg）时，动脉组织中检测到依维莫司。在安全性和疗效研究中，股浅动脉段随机分为高剂量（600 μg/cm(2)，n=16）、低剂量（300 μg/cm(2)，n=16）或配对未涂层球囊（高剂量 ZCB 对照组，n=16；低剂量 ZCB 对照组，n=16）。28 天时，所有测试组的血管造影狭窄百分比相似。组织学分析显示，与对照组相比，两组 ZCB 均减少了新生内膜形成（高剂量 ZCB 减少 44%，P=0.007；低剂量 ZCB 减少 22%，P=0.08）。在任何 ZCB 组中均未发现动脉愈合延迟或血管毒性的证据。
单次涂层球囊输送依维莫司是可行的，并且治疗水平可维持长达 28 天。ZCB 技术似乎可有效减少家族性高胆固醇血症猪股浅动脉的新生内膜增殖。
