Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model
Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model
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无创立体定向放射治疗猪模型去肾神经
DOI：
10.1016/j.jacc.2019.07.053
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发表时间：
2019-10-01
影响因子：
24
通讯作者：
Li, Yi-Gang
中科院分区：
文献类型：
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作者：
Cai, Xingxing;Yang, Yuli;Li, Yi-Gang
背景：在近期的随机对照试验中，基于导管的肾去神经支配术（RDN）在治疗高血压方面取得了有前景的结果。
目的：本研究旨在评估无创立体定向体部放疗（SBRT）作为一种肾去神经支配术方法的可行性、有效性和安全性。
方法：对12只正常血压猪的24条肾动脉进行SBRT，剂量分别为25戈瑞、35戈瑞和45戈瑞（每组各4条），另外4只猪作为对照。在基线时以及SBRT后7天、1个月和3个月获取血压（BP）、肾功能和血清去甲肾上腺素（NE）值。在安乐死前3个月进行腹部增强计算机断层扫描（CT）。测定肾NE浓度，并进行组织学分析以及针对酪氨酸羟化酶的免疫组化。
结果：SBRT操作在所有12只猪中均成功。各组间血压具有可比性。与对照组相比，治疗组在3个月时的血清和肾NE水平显著降低。此外，与对照组相比，SBRT导致神经损伤评分显著更高，酪氨酸羟化酶评分显著更低，而SBRT各剂量组之间无统计学差异。35戈瑞和45戈瑞产生的环形损伤明显大于25戈瑞。CT和组织学分析显示，接受35戈瑞和45戈瑞的动物出现更多的附带损伤，而25戈瑞组的附带损伤极小。
结论：在猪模型中，无创SBRT对于完全的环形肾去神经支配是可行且有效的，25戈瑞的剂量在短期内安全性最佳。（C）2019美国心脏病学会基金会
BACKGROUND Catheter-based renal denervation (RDN) has achieved promising outcomes to treat hypertension in recent randomized controlled trials.OBJECTIVES The purpose of this study was to assess the feasibility, efficacy, and safety of noninvasive stereotactic body radiotherapy (SBRT) as an approach for RDN.METHODS SBRT was performed in 24 renal arteries from 12 normotensive swine at doses of 25, 35, and 45 Gy (n = 4 each), and an additional 4 swine served as controls. Blood pressure (BP), renal function, and serum norepinephrine (NE) values were obtained at baseline and at 7 days, 1 month, and 3 months after SBRT. Abdominal contrast-enhanced computed tomography (CT) was performed after 3 months before euthanasia. Renal NE concentration was determined, and histological analysis and immunohistochemistry against tyrosine hydroxylase were performed.RESULTS SBRT procedure was successful in all 12 swine. BP was comparable among groups. Serum and renal NE levels at 3 months were significantly lower in treatment groups compared with control group. Furthermore, SBRT resulted in significantly greater nerve injury score and lower tyrosine hydroxylase score compared with control subjects, whereas there were no statistical differences between SBRT groups. Circumferential lesions created with 35 and 45 Gy were significantly greater than with 25 Gy. CT and histology analysis revealed that animals receiving 35 and 45 Gy experienced more collateral damage, which was minimal in the 25-Gy group.CONCLUSIONS Noninvasive SBRT was feasible and effective for complete, circumferential RDN in a swine model, with dosage at 25 Gy providing the safest short-term profile. (C) 2019 by the American College of Cardiology Foundation.