Levosimendan differentially modulates electrophysiological activities of sinoatrial nodes, pulmonary veins, and the left and right atria

Yung Kuo Lin, Yao Chang Chen, Yi Ann Chen, Jen Hung Huang, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Introduction: Calcium overload increases the risk of atrial fibrillation (AF). Levosimendan, a calcium sensitizer, increases myofilament contractility. Clinical reports suggested that levosimendan might increase AF occurrence, but the electrophysiological effects of levosimendan on AF substrates and triggers (pulmonary veins, PVs) are not clear. Methods and results: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial nodes (SANs), the left atrium (LA), and right atrium (RA) before and after application of different concentrations of levosimendan with or without milrinone (a phosphodiesterase [PDE] III inhibitor), and glibenclamide (an ATP-sensitive potassium channel [KATP] inhibitor). Levosimendan (0.03, 0.1, 0.3, and 1 μM) significantly increased spontaneous rates from 2.1 ± 0.2 to 2.5 ± 0.2, 2.5 ± 0.2, 2.5 ± 0.1, and 2.7 ± 0.2 Hz, respectively, in PVs (n = 10), but had no effects on denudated PVs (n = 9). Additionally, levosimendan significantly induced burst firing and/or triggered beats in intact PVs, but not in denudated PVs. In contrast, levosimendan at 0.3 and 1 μM increased the SAN spontaneous rate. In the presence of milrinone (10 μM), levosimendan (1 μM) did not increase the PV spontaneous activity. Moreover, glibenclamide (100 μM) prevented acceleration of the levosimendan-induced SAN and PV rates. In the LA, levosimendan at 0.3 and 1 μM shortened the AP duration, and increased contractility at 0.03, 0.1, 0.3, and 1 μM. In contrast, levosimendan did not change the RA contractility, and shortened the AP duration only at 1 μM. Conclusions: Levosimendan increased PV arrhythmogenesis through activating endothelial PDE III and the KATP, and modulating PV tension.

Original languageEnglish
Pages (from-to)1150-1158
Number of pages9
JournalJournal of Cardiovascular Electrophysiology
Issue number8
Publication statusPublished - Aug 2018


  • Atrial fibrillation
  • Atrium
  • Levosimendan
  • OR-1896
  • Pulmonary vein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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