Impact of renal denervation on atrial arrhythmogenic substrate in ischemic model of heart failure

Shinya Yamada, Man Cai Fong, Ya Wen Hsiao, Shih Lin Chang, Yung Nan Tsai, Li Wei Lo, Tze Fan Chao, Yenn Jiang Lin, Yu Feng Hu, Fa Po Chung, Jo Nan Liao, Yao Ting Chang, Hsing Yuan Li, Satoshi Higa, Shih Ann Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Background--Myocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction. Methods and Results--HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF-RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF-RDN. Left anterior descending coronary artery in HF and HF-RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real-time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF-RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF-RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3-kinase, AKT, and endothelial nitric oxide synthase in HF-RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF-RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF-RDN compared with HF (50% versus 100%, P < 0.05). Conclusions--RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase signaling pathway.

Original languageEnglish
Article numbere007312
JournalJournal of the American Heart Association
Volume7
Issue number2
DOIs
StatePublished - 1 Jan 2018

Keywords

  • Apoptosis
  • Atrial arrhythmogenic substrates
  • Atrial fibrillation
  • PI3K/AKT/eNOS signaling
  • Renal denervation

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