Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep
Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep
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DOI：
10.1161/hypertensionaha.114.04176
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发表时间：
2015-02-01
期刊：
影响因子：
8.3
通讯作者：
May, Clive N.
中科院分区：
文献类型：
--
作者：
Booth, Lindsea C.;Nishi, Erika E.;May, Clive N.
以往的研究表明，基于导管的肾脏去神经支配降低了人类顽固性高血压的血压和肾脏去甲肾上腺素溢出。该手术对传入感觉和传出交感肾神经的影响以及随后的神经再支配程度尚未研究。因此，我们使用Symplicity Flex导管检查了肾脏去神经后5.5个月和11个月的功能和解剖神经再支配水平。在血压正常的麻醉绵羊（n=6）中，电刺激完整的肾神经使动脉压从99 +/- 3 mmHg增加到107 +/- 3 mmHg（传入反应），并使肾血流量从198 +/- 16 mL/min减少到85 +/- 20 mL/min（传出反应）。在另一组（n=6），立即失神经支配后，肾交感神经活动的情况下，对电刺激的反应被取消。失神经后11个月（n=5），肾交感神经活动和对电刺激的反应处于正常水平。去神经后11个月，肾传出神经（酪氨酸羟化酶）和肾传入神经（降钙素基因相关肽）的免疫组织化学染色以及肾去甲肾上腺素水平均正常。去神经后5.5个月的结果相似（n=5）。总之，基于导管的肾去神经术有效地消融了血压正常绵羊的肾传入和传出神经。失神经支配后11个月，对电刺激的功能性传入和传出反应正常。在去神经后11个月的神经再支配支持的传入和传出肾神经的正常解剖分布。鉴于这一证据，需要重新评估基于导管的肾脏去神经支配在人类顽固性高血压中的长期抑制作用的机制。
Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99 +/- 3 to 107 +/- 3 mm Hg (afferent response) and reduced renal blood flow from 198 +/- 16 to 85 +/- 20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed.