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CT 引导下经动脉外周注射高渗盐水、长春新碱、紫杉醇和胍乙啶在猪模型中的肾去神经支配。

Renal denervation by CT-guided periarterial injection of hyperosmolar saline, vincristine, paclitaxel and guanethidine in a pig model.

机构信息

Department of Radiology, Charité Universitätsmedizin Berlin, Berlin, Germany.

出版信息

EuroIntervention. 2017 Apr 7;12(18):e2262-e2270. doi: 10.4244/EIJ-D-15-00354.

Abstract

AIMS

The aim of the study was to evaluate the feasibility, safety and efficacy of renal sympathetic denervation with CT-guided periarterial injection of potentially neurolytic agents in pigs.

METHODS AND RESULTS

Unilateral injection of formulations containing either 5M hyperosmolar saline, vincristine, paclitaxel or guanethidine around the renal artery was performed in 24 normotensive pigs with six animals per group. Needle placement and injections were performed under CT fluoroscopy guidance. Blood pressure measurements and CT scans were performed immediately before and after the intervention and four weeks after treatment. After euthanasia, norepinephrine (NE) concentrations of both kidneys were determined. The renal arteries and surrounding tissue were examined histologically to evaluate nerve fibre degeneration. Procedures were technically successful with good periarterial distribution of the injectant in all but one pig in the guanethidine group. No major adverse events or post-interventional complications occurred. In the vincristine group, NE concentrations of the renal parenchyma were lower on the treated side in all pigs with a mean decrease of 53% (38%-62%, p<0.01) compared to the contralateral control. Correspondingly, histological examination revealed neural degeneration in all animals treated with vincristine. In the other groups, no significant drop of NE values, or histological signs of nerve fibre degeneration were found.

CONCLUSIONS

CT-guided periarterial injection of the different substances was feasible and safe. Renal sympathetic denervation was achieved with vincristine. In contrast, hyperosmolar saline, paclitaxel and guanethidine do not seem to be appropriate for renal denervation in a pig model at the dosage used.

摘要

目的

本研究旨在评估 CT 引导下经动脉周围注射潜在神经溶解剂行肾去交感神经术的可行性、安全性和疗效。

方法和结果

24 只血压正常的猪被分为 6 组,每组 6 只,分别进行单侧肾动脉周围注射 5M 高渗盐水、长春新碱、紫杉醇或胍乙啶。在 CT 透视引导下进行置针和注射。在干预前和干预后即刻以及治疗 4 周后进行血压测量和 CT 扫描。处死动物后,测定双侧肾脏的去甲肾上腺素(NE)浓度。评估神经纤维退变情况,对肾动脉及其周围组织进行组织学检查。除胍乙啶组有 1 只猪外,其余所有猪的手术均成功完成,且药物均良好地分布于肾动脉周围。没有发生重大不良事件或术后并发症。在长春新碱组,所有猪的治疗侧肾实质 NE 浓度均低于对侧,平均降低 53%(38%-62%,p<0.01)。相应地,组织学检查显示所有长春新碱治疗的动物均存在神经退变。在其他组中,未发现 NE 值显著下降或神经纤维退变的组织学迹象。

结论

CT 引导下经动脉周围注射不同物质是可行且安全的。长春新碱可实现肾交感神经去神经支配。相比之下,高渗盐水、紫杉醇和胍乙啶在所用剂量下似乎不适合用于猪模型的肾去神经支配。

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