Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis

Chien Jung Chang, Chen Chuan Cheng, Ten-Fang Yang, Yao Chang Chen, Yung Kuo Lin, Shih Ann Chen, Yi Jen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of atrial fibrillation (AF). This study investigated whether selective and non-selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins and atria. Methods: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA), and right atrium (RA) preparations before and after celecoxib or indomethacin administration. A whole-cell patch clamp was used to record the sodium-calcium exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current (INa-late) before and after celecoxib administration in isolated PV cardiomyocytes. Results: Celecoxib (0.3, 1, and 3 μM) reduced PV spontaneous beating rates, and induced delayed afterdepolarizations and burst firings in four of eight PV preparations (50%, p b 0.05). Celecoxib also reduced SAN beating rates and decreased AP durations (APDs) in RA and LA, but did not change the resting membrane potential. Indomethacin (0.3, 1, 3, and 10 μM) changed neither the PV or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 μM) significantly increased the NCX current and decreased the ICa-L, but did not change the INa-late. Ranolazine (10 μM) suppressed celecoxib (3 μM)-induced PV burst firings in 6 (86%, p b 0.05) of 7 PVs. KB-R7943 (10 μM) suppressed celecoxib (3 μM)-induced PV burst firings in 5 (71%, p b 0.05) of 7 PVs. Conclusions: Selective and non-selective NSAIDs differentially modulate PV and atrial electrophysiological characteristics. Celecoxib increased PV triggered activity through enhancement of the NCX current, which contributed to its arrhythmogenesis.

Original languageEnglish
Pages (from-to)559-567
Number of pages9
JournalInternational Journal of Cardiology
Volume184
Issue number1
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Atrial fibrillation
  • Atrium
  • Celecoxib
  • Indomethacin
  • Pulmonary vein
  • Ranolazine

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