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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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
Publication statusPublished - 2015

Fingerprint

Celecoxib
Pulmonary Veins
Anti-Inflammatory Agents
Heart Atria
Pharmaceutical Preparations
Sinoatrial Node
Indomethacin
Action Potentials
Sodium-Calcium Exchanger
Microelectrodes
Cardiac Myocytes
Membrane Potentials
Atrial Fibrillation

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis. / Chang, Chien Jung; Cheng, Chen Chuan; Yang, Ten-Fang; Chen, Yao Chang; Lin, Yung Kuo; Chen, Shih Ann; Chen, Yi Jen.

In: International Journal of Cardiology, Vol. 184, No. 1, 2015, p. 559-567.

Research output: Contribution to journalArticle

Chang, Chien Jung ; Cheng, Chen Chuan ; Yang, Ten-Fang ; Chen, Yao Chang ; Lin, Yung Kuo ; Chen, Shih Ann ; Chen, Yi Jen. / Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis. In: International Journal of Cardiology. 2015 ; Vol. 184, No. 1. pp. 559-567.
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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.",
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T1 - Selective and non-selective non-steroidal anti-inflammatory drugs differentially regulate pulmonary vein and atrial arrhythmogenesis

AU - Chang, Chien Jung

AU - Cheng, Chen Chuan

AU - Yang, Ten-Fang

AU - Chen, Yao Chang

AU - Lin, Yung Kuo

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Atrial fibrillation

KW - Atrium

KW - Celecoxib

KW - Indomethacin

KW - Pulmonary vein

KW - Ranolazine

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