Anatomic assessment of sympathetic peri-arterial renal nerves in man

Kenichi Sakakura; Elena Ladich; Qi Cheng; Fumiyuki Otsuka; Kazuyuki Yahagi; David R. Fowler; Frank D. Kolodgie; Renu Virmani; Michael Joner

doi:10.1016/j.jacc.2014.03.059

Anatomic assessment of sympathetic peri-arterial renal nerves in man

Kenichi Sakakura, Elena Ladich, Qi Cheng, Fumiyuki Otsuka, Kazuyuki Yahagi, David R. Fowler, Frank D. Kolodgie, Renu Virmani, Michael Joner

Research output: Contribution to journal › Article › peer-review

327 Scopus citations

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.

Original language	English
Pages (from-to)	635-643
Number of pages	9
Journal	Journal of the American College of Cardiology
Volume	64
Issue number	7
DOIs	https://doi.org/10.1016/j.jacc.2014.03.059
State	Published - 19 Aug 2014
Externally published	Yes

Keywords

anatomy
pathology
renal denervation
sympathetic nerve

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10.1016/j.jacc.2014.03.059

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@article{4088deff6ed441bab21ca2abff8c66f3,

title = "Anatomic assessment of sympathetic peri-arterial renal nerves in man",

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.",

keywords = "anatomy, pathology, renal denervation, sympathetic nerve",

author = "Kenichi Sakakura and Elena Ladich and Qi Cheng and Fumiyuki Otsuka and Kazuyuki Yahagi and Fowler, {David R.} and Kolodgie, {Frank D.} and Renu Virmani and Michael Joner",

note = "Funding Information: 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. ",

year = "2014",

month = aug,

day = "19",

doi = "10.1016/j.jacc.2014.03.059",

language = "English",

volume = "64",

pages = "635--643",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Anatomic assessment of sympathetic peri-arterial renal nerves in man

AU - Sakakura, Kenichi

AU - Ladich, Elena

AU - Cheng, Qi

AU - Otsuka, Fumiyuki

AU - Yahagi, Kazuyuki

AU - Fowler, David R.

AU - Kolodgie, Frank D.

AU - Virmani, Renu

AU - Joner, Michael

N1 - Funding Information: 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.

PY - 2014/8/19

Y1 - 2014/8/19

N2 - 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.

AB - 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.

KW - anatomy

KW - pathology

KW - renal denervation

KW - sympathetic nerve

UR - http://www.scopus.com/inward/record.url?scp=84905981330&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2014.03.059

DO - 10.1016/j.jacc.2014.03.059

M3 - Article

C2 - 25125292

AN - SCOPUS:84905981330

SN - 0735-1097

VL - 64

SP - 635

EP - 643

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 7

ER -

Anatomic assessment of sympathetic peri-arterial renal nerves in man

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Keywords

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