Rivaroxaban modulates electrical and mechanical characteristics of left atrium

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD§ssub§ 90§esub§) from 76 ± 2 to 79 ± 3, 67 ± 4 (P <0.05, vs. control), 59 ± 5, (P <0.01, vs. control), and 56 ± 4 ms (P <0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P <0.05, vs. control), 563 ± 136 (P <0.05, vs. control), 582 ± 119 (P <0.05, vs. control), and 603 ± 108 mg (P <0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD§ssub§90§esub§ from 73 ± 2 to 60 ± 6 ms (P <0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.

Original languageEnglish
Article number17
JournalJournal of Biomedical Science
Volume20
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

Heart Atria
Potassium
Cardiac Myocytes
Atrial Fibrillation
Action Potentials
Rivaroxaban
Microelectrodes
NG-Nitroarginine Methyl Ester
Clamping devices
Indomethacin
Calcium
Stroke
Rabbits

Keywords

  • Atrial fibrillation
  • Cyclooxygenase
  • Factor Xa
  • Nitric oxide synthase
  • Rivaroxaban

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Rivaroxaban modulates electrical and mechanical characteristics of left atrium. / Chang, Chien Jung; Chen, Yao Chang; Lin, Yung Kuo; Huang, Jen Hung; Chen, Shih Ann; Chen, Yi Jen.

In: Journal of Biomedical Science, Vol. 20, No. 1, 17, 2013.

Research output: Contribution to journalArticle

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abstract = "Background: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90{\%} repolarization (APD§ssub§ 90§esub§) from 76 ± 2 to 79 ± 3, 67 ± 4 (P <0.05, vs. control), 59 ± 5, (P <0.01, vs. control), and 56 ± 4 ms (P <0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P <0.05, vs. control), 563 ± 136 (P <0.05, vs. control), 582 ± 119 (P <0.05, vs. control), and 603 ± 108 mg (P <0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD§ssub§90§esub§ from 73 ± 2 to 60 ± 6 ms (P <0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.",
keywords = "Atrial fibrillation, Cyclooxygenase, Factor Xa, Nitric oxide synthase, Rivaroxaban",
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T1 - Rivaroxaban modulates electrical and mechanical characteristics of left atrium

AU - Chang, Chien Jung

AU - Chen, Yao Chang

AU - Lin, Yung Kuo

AU - Huang, Jen Hung

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2013

Y1 - 2013

N2 - Background: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD§ssub§ 90§esub§) from 76 ± 2 to 79 ± 3, 67 ± 4 (P <0.05, vs. control), 59 ± 5, (P <0.01, vs. control), and 56 ± 4 ms (P <0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P <0.05, vs. control), 563 ± 136 (P <0.05, vs. control), 582 ± 119 (P <0.05, vs. control), and 603 ± 108 mg (P <0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD§ssub§90§esub§ from 73 ± 2 to 60 ± 6 ms (P <0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.

AB - Background: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. Results: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD§ssub§ 90§esub§) from 76 ± 2 to 79 ± 3, 67 ± 4 (P <0.05, vs. control), 59 ± 5, (P <0.01, vs. control), and 56 ± 4 ms (P <0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P <0.05, vs. control), 563 ± 136 (P <0.05, vs. control), 582 ± 119 (P <0.05, vs. control), and 603 ± 108 mg (P <0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD§ssub§90§esub§ from 73 ± 2 to 60 ± 6 ms (P <0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. Conclusions: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.

KW - Atrial fibrillation

KW - Cyclooxygenase

KW - Factor Xa

KW - Nitric oxide synthase

KW - Rivaroxaban

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