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优化利福平涂层于覆膜涤纶血管内移植物治疗感染性主动脉瘤。

Optimization of rifampin coating on covered Dacron endovascular stent grafts for infected aortic aneurysms.

机构信息

Division of Interventional Radiology, Department of Medical Imaging, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Biointerfaces Institute, McMaster University, Hamilton, Ontario, Canada.

出版信息

J Vasc Surg. 2019 Jan;69(1):242-248.e1. doi: 10.1016/j.jvs.2017.10.069. Epub 2018 Mar 1.

Abstract

OBJECTIVE

In the treatment of an infected aorta, open repair and replacement with a rifampin-impregnated Dacron vascular graft decrease the risk of prosthetic graft infections, with several protocols available in the literature. We hypothesize that the same holds true for endovascular aneurysm repair, and after studying and optimizing rifampin solution concentration and incubation period to maximize the coating process of rifampin on Dacron endovascular stent grafts (ESGs), we propose a rapid real-time perioperative protocol.

METHODS

Several prepared rifampin solutions, including a negative control solution, were used to coat multiple triplicate sets of Dacron endovascular aortic stent grafts at different but set incubation periods. Rifampin elution from the grafts was studied by spectroscopic analysis. Once an optimized solution concentration and incubation time were determined, the elution of rifampin over time from the graft and the graft's surface characteristics were studied by ultraviolet-visible spectroscopy and atomic force microscopy.

RESULTS

All coated ESGs with any concentration of prepared rifampin solution, regardless of incubation time, immediately demonstrated a visible bright orange discoloration and subsequently after elution procedures returned to the original noncolored state. At the 25-minute incubation time (standard flush), there was no statistical difference in the amount of rifampin coated to the ESGs with 10-mg/mL, 30-mg/mL, and 60-mg/mL solutions (0.06 ± 0.01, 0.07 ± 0.05, and 0.044 ± 0.01, respectively; P > .05). This was also true for a 10-minute incubation time (express flush) of 10-mg/mL and 60-mg/mL rifampin solution concentrations (0.04 ± 0.007 and 0.066 ± 0.014, respectively; P = .22). The elution-over-time of coated rifampin ESG, although not statistically significant, did seem to plateau and to reach a steady state by 50 hours and was confirmed by surface characteristics using atomic force microscopy.

CONCLUSIONS

Having studied two variables of rifampin coating techniques to Dacron ESGs, the authors propose a rapid real-time perioperative coating protocol by using a 10-mg/mL rifampin solution for a 10-minute incubation period. As rifampin loosely binds to Dacron ESGs by weak intermolecular forces, a rifampin-coated ESG would need to be inserted in a timely fashion to treat the diseased aorta and to deliver its antibiotic affect. A rapid perioperative coating protocol followed by immediate deployment makes our proposed technique especially useful in an urgent and unstable clinical scenario.

摘要

目的

在感染性主动脉的治疗中,使用利福平浸渍的涤纶血管移植物进行开放修复和置换可降低人工移植物感染的风险,文献中有多种方案可供选择。我们假设血管内动脉瘤修复也同样如此,在研究并优化利福平溶液浓度和孵育时间以最大限度地提高利福平在涤纶血管内支架移植物(ESG)上的涂层过程后,我们提出了一种快速实时围手术期方案。

方法

使用几种已制备的利福平溶液(包括阴性对照溶液),在不同但设定的孵育期内对多组重复的涤纶血管内主动脉支架移植物进行涂层。通过光谱分析研究利福平从移植物中的洗脱情况。一旦确定了优化的溶液浓度和孵育时间,就通过紫外可见光谱和原子力显微镜研究利福平随时间从移植物中的洗脱情况以及移植物的表面特性。

结果

所有用任何浓度的已制备利福平溶液进行涂层的 ESG,无论孵育时间如何,都会立即显示出明显的亮橙色变色,随后在洗脱过程后恢复到原始非着色状态。在 25 分钟的孵育时间(标准冲洗)下,用 10mg/ml、30mg/ml 和 60mg/ml 溶液涂层的 ESG 中利福平的量没有统计学差异(分别为 0.06±0.01、0.07±0.05 和 0.044±0.01;P>.05)。在 10 分钟孵育时间(快速冲洗)下,10mg/ml 和 60mg/ml 利福平溶液浓度的结果也是如此(分别为 0.04±0.007 和 0.066±0.014;P=0.22)。尽管涂层利福平 ESG 的洗脱时间没有统计学意义,但似乎在 50 小时时达到了稳定状态,并通过原子力显微镜的表面特性得到了证实。

结论

在对涤纶 ESG 的两种利福平涂层技术变量进行研究后,作者提出了一种快速实时的围手术期涂层方案,即使用 10mg/ml 的利福平溶液进行 10 分钟的孵育。由于利福平通过弱分子间力松散地结合在涤纶 ESG 上,因此需要及时插入利福平涂层的 ESG 来治疗患病的主动脉并发挥其抗生素作用。快速的围手术期涂层方案随后立即进行部署,这使得我们提出的技术在紧急和不稳定的临床情况下特别有用。

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