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. 2017 Mar 2;6(3):e004479.
doi: 10.1161/JAHA.116.004479.

Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy

Shinya Yamada  1   2 , Li-Wei Lo  3   4 , Yu-Hui Chou  1 , Wei-Lun Lin  1   4 , Shih-Lin Chang  1   4 , Yenn-Jiang Lin  1   4 , Shin-Huei Liu  1   4 , Wen-Han Cheng  1   4 , Tsung-Ying Tsai  1   4 , Shih-Ann Chen  3   4
Affiliations

Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy

Shinya Yamada et al. J Am Heart Assoc. .

Abstract

Background: Frequent ventricular premature complexes (VPCs) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (RDN) may protect the heart from remodeling. This study aimed to investigate the effect of frequent VPCs on structural and electrical properties and whether RDN can protect the heart from remodeling.

Methods and results: Eighteen rabbits were randomized to control (n=6), VPC (n=6), and VPC-RDN (n=6) groups. Surgical and chemical RDNs were approached through bilateral retroperitoneal flank incisions in the VPC-RDN group. Pacemakers were implanted to the left ventricular apex to produce 50% VPC burden for 5 weeks in the VPC and VPC-RDN groups. In addition, ventricular myocardium was harvested for western blot and trichrome stain. Echocardiographic results showed left ventricular enlargement after 5-week pacing in the VPC group, but not in the VPC-RDN group, when compared to baseline. In biventricles, ion channel protein expressions of Nav1.5, Cav1.2, Kir2.1, and SERCA2 were similar among 3 groups. However, the degree of biventricular fibrosis was extensive in the VPC group, compared to the control and VPC-RDN groups. Importantly, ventricular fibrillation inducibility was higher in the VPC group (41%) when comparing to the control (13%; P<0.05) and VPC-RDN groups (13%; P<0.05), respectively.

Conclusions: Frequent VPCs are associated with the development of cardiac structural remodeling and high ventricular fibrillation inducibility. RDN prevents cardiac remodeling and the occurrence of ventricular arrhythmia through antifibrosis.

Keywords: antifibrosis; remodeling; renal denervation; ventricular arrhythmia.

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Figures

Figure 1
Figure 1
Renal artery sympathetic denervation procedure. Renal vessels were exposed (A) and renal artery is dissected (B) with removal of peripheral fat (C) and then application of gauge with phenol solution for 10 to 15 minutes (D).
Figure 2
Figure 2
Left ventricular function from echocardiographic examination during a 5‐week follow‐up. A, LVEF at baseline and the end of a 5‐week pacing in VPC rabbits and VPC‐RDN rabbits. B, LVEDD at baseline and the end of a 5‐week pacing in VPC rabbits and VPC‐RDN rabbits. C, LVESD at baseline and the end of a 5‐week pacing in VPC rabbits and VPC‐RDN rabbits. LVEDD indicates left ventricular end‐diastolic diameter; LVEF, left ventricular ejection fraction; LVESD, left ventricular end‐systolic diameter; RDN, renal artery sympathetic denervation; VPC, ventricular premature complex.
Figure 3
Figure 3
Ion channel protein expressions of NaV1.5, CaV1.2, Kir2.1, and SERCA2 in right ventricle (RV) and left ventricle (LV). A, Protein expression of NaV1.5, CaV1.2, Kir2.1, and SERCA2 among 3 groups in LV (left panel). Right panel shows the representative western blots of the protein sample extracts from the LV. B, Protein expression of NaV1.5, CaV1.2, Kir2.1, and SERCA2 among 3 groups in RV (left panel). Right panel shows the representative western blots of the protein sample extracts from the RV. RDN indicates renal artery sympathetic denervation; VPC, ventricular premature complex.
Figure 4
Figure 4
Quantitative analysis of fibrotic area in the ventricle and atrium among all groups. The collagen area was calculated as a percentage of the total ventricular or atrial myocardial area. A, Trichrome stain results of the left and right ventricle. B, Trichrome stain results of the left and right atrium. RDN indicates renal artery sympathetic denervation; VPC, ventricular premature complex.
Figure 5
Figure 5
Ventricular and atrial tissue fibrosis detected with Masson's trichrome staining among all groups. A, Control rabbits left ventricle; (B) VPC rabbits left ventricle; (C) VPC‐RDN rabbits left ventricle; (D) control rabbits right ventricle; (E) VPC rabbits right ventricle; (F) VPC‐RDN rabbits right ventricle; (G) control rabbits left atrium; (H) VPC rabbits left atrium; (I) VPC‐RDN rabbits left atrium; (J) control rabbits right atrium; (K) VPC rabbits right atrium; and (L) VPC‐RDN rabbits right atrium. Blue color represents the collagen component, whereas the red color is the normal ventricular or atrial myocardium. RDN indicates renal artery sympathetic denervation; VPC, ventricular premature complex.
Figure 6
Figure 6
Immunohistochemistry staining in the ventricle. A, control rabbits left ventricle; (B) VPC rabbits left ventricle; (C) VPC‐RDN rabbits left ventricle; (D) control rabbits right ventricle; (E) VPC rabbits right ventricle; and (F) VPC‐RDN rabbits right ventricle. Tyrosine hydroxylase staining in biventricle showing increased sympathetic innervation in VPC rabbits compared with control rabbits and VPC‐RDN rabbits. RDN indicates renal artery sympathetic denervation; VPC, ventricular premature complex.
Figure 7
Figure 7
Cardiac sympathetic activity in the ventricle from 3 groups. Sympathetic neuron marker densities in left ventricle and right ventricle were significantly higher in VPC rabbits compared with those of control and VPC‐RDN rabbits, respectively. RDN indicates renal artery sympathetic denervation; VPC, ventricular premature complex.
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