B-Type Natriuretic Peptide Modulates Pulmonary Vein Arrhythmogenesis

A Novel Potential Contributor to the Genesis of Atrial Tachyarrhythmia in Heart Failure

Yung-Kuo Lin, Yao Chang Chen, Yi Ann Chen, Yung Hsin Yeh, Shih Ann Chen, Yi-Jen Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Heart failure (HF) plays a critical role in the genesis of atrial fibrillation (AF). A high B-type natriuretic peptide (BNP) level occurs in patients with HF and in patients with AF. However, the role of BNP in the pathophysiology of AF is not clear. The purposes of this study were to evaluate the effects of BNP on pulmonary vein (PV) arrhythmogenesis. Methods and Results: Whole-cell patch clamp and fluorescence were used to study the action potential, ionic currents, and calcium homeostasis in isolated single rabbit PV cardiomyocytes before and after a BNP infusion, with or without ODQ (10 μM), milrinone (50 μM), or ouabain (1 μM). BNP increased PV spontaneous activity by 28.2 ± 7.5% at 100 nM and by 23.8 ± 9.1% at 300 nM. Similar to those with BNP, milrinone 50 μM increased the PV beating rate from 3.0 ± 0.2 to 3.6 ± 0.3 Hz (P < 0.0005, n = 7). In the presence of ODQ application, BNP didn't change PV spontaneous activity. BNP (100 nM) increased calcium transients (F/F0 from 1.6 ± 0.1 to 1.9 ± 0.2, n = 20, P < 0.05) and increased the pacemaker current (0.4 ± 0.1 to 1.0 ± 0.2 pA/pF, n = 17, P < 0.0005) in PV cardiomyocytes. Moreover, BNP (100 nM) increased the transient inward current, sodium currents, sodium-calcium exchanger currents, and L-type calcium current; but reduced late sodium currents and the Na-K pump in PV cardiomyocytes. Conclusion: BNP increases PV arrhythmogenesis, which may contribute to the genesis of atrial tachyarrhythmogenesis in HF. Cyclic GMP activation, phosphodiesterase 3 inhibition and Na+/K+-ATPase inhibition might participate in the BNP modulation of PV electrophysiology.

Original languageEnglish
Pages (from-to)1462-1471
Number of pages10
JournalJournal of Cardiovascular Electrophysiology
Volume27
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Pulmonary Veins
Brain Natriuretic Peptide
Tachycardia
Heart Failure
Cardiac Myocytes
Milrinone
Atrial Fibrillation
Calcium
Sodium
Sodium-Calcium Exchanger
Electrophysiology
Cyclic GMP
Phosphoric Diester Hydrolases
Ouabain
Action Potentials
Homeostasis
Fluorescence
Rabbits

Keywords

  • atrial fibrillation
  • B-type natriuretic peptide
  • heart failure
  • pulmonary vein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

B-Type Natriuretic Peptide Modulates Pulmonary Vein Arrhythmogenesis : A Novel Potential Contributor to the Genesis of Atrial Tachyarrhythmia in Heart Failure. / Lin, Yung-Kuo; Chen, Yao Chang; Chen, Yi Ann; Yeh, Yung Hsin; Chen, Shih Ann; Chen, Yi-Jen.

In: Journal of Cardiovascular Electrophysiology, Vol. 27, No. 12, 01.12.2016, p. 1462-1471.

Research output: Contribution to journalArticle

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abstract = "Background: Heart failure (HF) plays a critical role in the genesis of atrial fibrillation (AF). A high B-type natriuretic peptide (BNP) level occurs in patients with HF and in patients with AF. However, the role of BNP in the pathophysiology of AF is not clear. The purposes of this study were to evaluate the effects of BNP on pulmonary vein (PV) arrhythmogenesis. Methods and Results: Whole-cell patch clamp and fluorescence were used to study the action potential, ionic currents, and calcium homeostasis in isolated single rabbit PV cardiomyocytes before and after a BNP infusion, with or without ODQ (10 μM), milrinone (50 μM), or ouabain (1 μM). BNP increased PV spontaneous activity by 28.2 ± 7.5{\%} at 100 nM and by 23.8 ± 9.1{\%} at 300 nM. Similar to those with BNP, milrinone 50 μM increased the PV beating rate from 3.0 ± 0.2 to 3.6 ± 0.3 Hz (P < 0.0005, n = 7). In the presence of ODQ application, BNP didn't change PV spontaneous activity. BNP (100 nM) increased calcium transients (F/F0 from 1.6 ± 0.1 to 1.9 ± 0.2, n = 20, P < 0.05) and increased the pacemaker current (0.4 ± 0.1 to 1.0 ± 0.2 pA/pF, n = 17, P < 0.0005) in PV cardiomyocytes. Moreover, BNP (100 nM) increased the transient inward current, sodium currents, sodium-calcium exchanger currents, and L-type calcium current; but reduced late sodium currents and the Na-K pump in PV cardiomyocytes. Conclusion: BNP increases PV arrhythmogenesis, which may contribute to the genesis of atrial tachyarrhythmogenesis in HF. Cyclic GMP activation, phosphodiesterase 3 inhibition and Na+/K+-ATPase inhibition might participate in the BNP modulation of PV electrophysiology.",
keywords = "atrial fibrillation, B-type natriuretic peptide, heart failure, pulmonary vein",
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T2 - A Novel Potential Contributor to the Genesis of Atrial Tachyarrhythmia in Heart Failure

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AU - Chen, Yao Chang

AU - Chen, Yi Ann

AU - Yeh, Yung Hsin

AU - Chen, Shih Ann

AU - Chen, Yi-Jen

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N2 - Background: Heart failure (HF) plays a critical role in the genesis of atrial fibrillation (AF). A high B-type natriuretic peptide (BNP) level occurs in patients with HF and in patients with AF. However, the role of BNP in the pathophysiology of AF is not clear. The purposes of this study were to evaluate the effects of BNP on pulmonary vein (PV) arrhythmogenesis. Methods and Results: Whole-cell patch clamp and fluorescence were used to study the action potential, ionic currents, and calcium homeostasis in isolated single rabbit PV cardiomyocytes before and after a BNP infusion, with or without ODQ (10 μM), milrinone (50 μM), or ouabain (1 μM). BNP increased PV spontaneous activity by 28.2 ± 7.5% at 100 nM and by 23.8 ± 9.1% at 300 nM. Similar to those with BNP, milrinone 50 μM increased the PV beating rate from 3.0 ± 0.2 to 3.6 ± 0.3 Hz (P < 0.0005, n = 7). In the presence of ODQ application, BNP didn't change PV spontaneous activity. BNP (100 nM) increased calcium transients (F/F0 from 1.6 ± 0.1 to 1.9 ± 0.2, n = 20, P < 0.05) and increased the pacemaker current (0.4 ± 0.1 to 1.0 ± 0.2 pA/pF, n = 17, P < 0.0005) in PV cardiomyocytes. Moreover, BNP (100 nM) increased the transient inward current, sodium currents, sodium-calcium exchanger currents, and L-type calcium current; but reduced late sodium currents and the Na-K pump in PV cardiomyocytes. Conclusion: BNP increases PV arrhythmogenesis, which may contribute to the genesis of atrial tachyarrhythmogenesis in HF. Cyclic GMP activation, phosphodiesterase 3 inhibition and Na+/K+-ATPase inhibition might participate in the BNP modulation of PV electrophysiology.

AB - Background: Heart failure (HF) plays a critical role in the genesis of atrial fibrillation (AF). A high B-type natriuretic peptide (BNP) level occurs in patients with HF and in patients with AF. However, the role of BNP in the pathophysiology of AF is not clear. The purposes of this study were to evaluate the effects of BNP on pulmonary vein (PV) arrhythmogenesis. Methods and Results: Whole-cell patch clamp and fluorescence were used to study the action potential, ionic currents, and calcium homeostasis in isolated single rabbit PV cardiomyocytes before and after a BNP infusion, with or without ODQ (10 μM), milrinone (50 μM), or ouabain (1 μM). BNP increased PV spontaneous activity by 28.2 ± 7.5% at 100 nM and by 23.8 ± 9.1% at 300 nM. Similar to those with BNP, milrinone 50 μM increased the PV beating rate from 3.0 ± 0.2 to 3.6 ± 0.3 Hz (P < 0.0005, n = 7). In the presence of ODQ application, BNP didn't change PV spontaneous activity. BNP (100 nM) increased calcium transients (F/F0 from 1.6 ± 0.1 to 1.9 ± 0.2, n = 20, P < 0.05) and increased the pacemaker current (0.4 ± 0.1 to 1.0 ± 0.2 pA/pF, n = 17, P < 0.0005) in PV cardiomyocytes. Moreover, BNP (100 nM) increased the transient inward current, sodium currents, sodium-calcium exchanger currents, and L-type calcium current; but reduced late sodium currents and the Na-K pump in PV cardiomyocytes. Conclusion: BNP increases PV arrhythmogenesis, which may contribute to the genesis of atrial tachyarrhythmogenesis in HF. Cyclic GMP activation, phosphodiesterase 3 inhibition and Na+/K+-ATPase inhibition might participate in the BNP modulation of PV electrophysiology.

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