Anatomic Assessment of Sympathetic Peri-Arterial Renal Nerves in Man

doi:10.1016/j.jacc.2014.03.059

Journal of the American College of Cardiology

Volume 64, Issue 7, 19 August 2014, Pages 635-643

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Abstract

Background

Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood.

Objectives

The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries.

Methods

Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti–tyrosine hydroxylase and anti–calcitonin gene–related peptide.

Results

A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p < 0.001). The mean number of nerves in the ventral region (11.0 ± 3.5 per section) was greater compared with the dorsal region (6.2 ± 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene–related peptide ratio 25.1 ± 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients.

Conclusions

The density of peri-arterial renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures.

Key Words

anatomy

pathology

renal denervation

sympathetic nerve

Abbreviations and Acronyms

blood pressure

CGRP

calcitonin gene–related peptide

H&E

hematoxylin and eosin

NFP

neurofilament protein

tyrosine hydroxylase

Cited by (0)

: This work was supported in part by Medtronic Cardiovascular (Santa Rosa, California), but the manuscript was prepared independently by CVPath Institute, Inc., a private nonprofit research organization. Dr. Sakakura is supported by a research fellowship from the Banyu Life Science Foundation International; and has received speaking honoraria from Abbott Vascular, Boston Scientific, and Medtronic Cardiovascular. Dr. Virmani has received research support from 480 Biomedical, Abbott Vascular, Atrium, Biosensors International, Biotronik, Boston Scientific, Cordis J&J, GlaxoSmithKline, Kona, Medtronic, Microport Medical, OrbusNeich Medical, ReCor, SINO Medical Technology, Terumo Corporation, and W.L. Gore; has speaking engagements with Merck; receives honoraria from 480 Biomedical, Abbott Vascular, Biosensors International, Boston Scientific, CeloNova, Claret Medical, Cordis J&J, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Joner is a consultant for Biotronik and Cardionovum; and has received speaking honoraria from Abbott Vascular, Biotronik, Cordis J&J, Medtronic, and St. Jude. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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