Renal denervation decreases susceptibility of the heart to ventricular fibrillation in a canine model of chronic kidney disease

Abstract

What is the central question of this study? Renal denervation (RDN) has been shown to be effective and safe, resulting in better control of blood pressure and an improvement in left ventricular hypertrophy in chronic kidney disease (CKD) patients. Ventricular arrhythmias and sudden cardiac death are common causes of death in CKD patients, but previous studies pay almost no attention to the effects of RDN on the risk of ventricular fibrillation associated with CKD. What is the main finding and its importance? Renal denervation could decrease susceptibility of the heart to ventricular fibrillation in a canine CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects. Renal denervation (RDN) has been shown to have therapeutic value in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether RDN could decrease the susceptibility of the heart to ventricular fibrillation in a canine model of CKD. Twenty-one dogs were used. Chronic kidney disease was produced by subtotal nephrectomy in 16 dogs with RDN treatment (CKD + RDN group, n = 8) or sham RDN (CKD group, n = 8). Another five dogs underwent sham operation and sham RDN to serve as controls (CTR group). Parameters of renal function, blood pressure, echocardiography, ECG, noradrenaline and inflammation were measured at baseline and 6 weeks after the surgical procedure. The ventricular fibrillation threshold (VFT) was determined at the end of the study. Subtotal nephrectomy successfully induced a canine CKD model. When compared with the CTR group, subtotal nephrectomy in the CKD group significantly elevated blood pressure; increased the left ventricular mass, end-diastolic left ventricular internal dimension, left ventricular end-diastolic posterior wall thickness and end-diastolic interventricular septum thickness; prolonged the QT interval, corrected QT interval, the interval from the peak to the end of the T wave (Tp-e) and the corrected Tp-e interval; and increased the QT dispersion and the Tp-e/QT ratio; decreased the VFT; and increased the serum concentrations of noradrenaline, C-reactive protein and interleukin-6. Renal denervation significantly attenuated these changes induced by CKD. The study demonstrated that RDN could decrease the susceptibility of the heart to ventricular fibrillation in this CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects.

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“…33,34 Additionally, animal experiments reported that CKD could lead to increasing vulnerability to lethal ventricular arrhythmia. 35,36 Similarly, the results for Group 3, who had a higher eGFR value than that in other groups, found that the proportion of ROSC at hospital arrival was high. Therefore, it might be reasoned that the patients in Groups 1 or 2 would have a high possibility of reoccurrence or sustaining of the VF, even if defibrillation were performed, and that they would have poor neurological outcomes.…”

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“…Of course, there are also models for electrical heart disease without induction of heart failure. Dogs with drug‐induced long QT syndrome (LQTS) and kidney disease achieved by renal infarction are highly inducible for ventricular arrhythmias by pacing protocols or sympathetic challenge (Gallacher et al, 2007 ; Levine et al, 1985 ; Tang et al, 2017 ). LQTS and kidney disease are also well‐known clinical conditions that predispose the occurrence of ventricular arrhythmias.…”

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“…Similar findings were reported with experimental hypertension in mice [ 52 ]. In addition, Tang and co-workers recently reported an increased risk of ventricular fibrillation in dogs with CKD, which was attenuated by renal denervation [ 53 ]. These results were attributed to reduced left ventricle (LV) hypertrophy, sympathetic activation, and inflammation.…”