Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model

Shin-Huei Liu; Li-Wei Lo; Yu-Hui Chou; Wei-Lun Lin; Tseng-Ying Tsai; Wen-Han Cheng; Shinya Yamada; Shih-Ann Chen

doi:10.1016/j.hrthm.2021.05.014

Renal denervation prevents myocardial structural remodeling and arrhythmogenicity in a chronic kidney disease rabbit model

Heart Rhythm. 2021 Sep;18(9):1596-1604. doi: 10.1016/j.hrthm.2021.05.014. Epub 2021 May 13.

Authors

Shin-Huei Liu¹, Li-Wei Lo², Yu-Hui Chou¹, Wei-Lun Lin¹, Tseng-Ying Tsai¹, Wen-Han Cheng¹, Shinya Yamada³, Shih-Ann Chen⁴

Affiliations

¹ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Institute, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Institute, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: gyrus@ms65.hinet.net.
³ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Institute of Clinical Medicine and Cardiovascular Research Institute, National Yang Ming Chiao Tung University, Taipei, Taiwan; Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

PMID: 33992732
DOI: 10.1016/j.hrthm.2021.05.014

Abstract

Background: The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear.

Objective: The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD.

Methods: Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated.

Results: The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P <.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (10² μm²/mm²), P <.01; 4.1 ± 1.8 vs 0.9± 0.6 (10² μm²/mm²), P <.01; right ventricle: 3.6 ± 1.0 vs 1.0 ± 0.4 (10² μm²/mm²), P <.01; 3.6 ± 1.0 vs 1.0 ± 0.5 (10² μm²/mm²), P <.01].

Conclusion: Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

Keywords: Autonomic dysfunction; Cardiac remodeling; Chronic kidney disease; Renal artery denervation; Ventricular arrhythmia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arrhythmias, Cardiac / etiology
Arrhythmias, Cardiac / prevention & control
Atrial Remodeling
Autonomic Denervation / methods*
Cardiomyopathies* / etiology
Cardiomyopathies* / prevention & control
Electrophysiologic Techniques, Cardiac / methods
Fibrosis
Heart Ventricles* / pathology
Heart Ventricles* / physiopathology
Kidney / blood supply*
Models, Animal
Rabbits
Renal Artery / innervation*
Renal Insufficiency, Chronic* / complications
Renal Insufficiency, Chronic* / physiopathology
Renal Insufficiency, Chronic* / surgery
Treatment Outcome
Ventricular Remodeling / physiology