Heart Failure Differentially Modulates the Effects of Ivabradine on the Electrical Activity of the Sinoatrial Node and Pulmonary Veins

Chao Shun Chan, Yao Chang Chen, Shih Lin Chang, Yung Kuo Lin, Yu Hsun Kao, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Ivabradine increases the risk of atrial fibrillation (AF). Heart failure (HF) or sinoatrial node (SAN) dysfunction increases the risk of AF, and pulmonary veins (PVs) play a critical role in the pathophysiology of AF. This study investigated the electrophysiologic effects of ivabradine on SANs and PVs in a rabbit model of HF. Methods and Results: Conventional microelectrodes were used to simultaneously record the electrical activities and conduction properties of control and HF rabbit SAN-PV preparations before and after perfusion with ivabradine (0.1, 1, or 10 μmol/L), either alone or with isoproterenol (1 μmol/L). HF SANs exhibited a lower beating rate than the control SANs. SAN automaticity exit blocks and SAN-PV conduction blocks were observed in 25% and 50% of samples, respectively, with P <.05 for HF SANs (n = 8) but not for control SANs (n = 6). Delayed afterdepolarization (DAD) was observed in 37.5% of HF PVs but not in control PVs. HF PVs exhibited a faster beating rate and more severe fibrosis than control PVs. Ivabradine reduced the SAN beating rates and increased the occurrences of SAN-PV conduction blocks and PV DADs in control and HF preparations. However, ivabradine induced SAN automaticity exit blocks only in HF preparations. Isoproterenol induced PV burst firing and shifting electrical conduction in control and HF preparations. A combination of isoproterenol and ivabradine (10 μmol/L) in HF preparations resulted in the highest incidences of PV burst firing and SAN-PV electrical shifting. Conclusions: HF differentially modulates the effects of ivabradine on the electrical activities of SAN and PVs, which may increase PV arrhythmogenesis and contribute to the risk of AF in HF patients.

Original languageEnglish
Pages (from-to)763-772
Number of pages10
JournalJournal of Cardiac Failure
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Atrial fibrillation
  • heart failure
  • ivabradine
  • pulmonary veins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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