Testosterone replacement increases aged pulmonary vein and left atrium arrhythmogenesis with enhanced adrenergic activity

Wen Chin Tsai, Ting-I Lee, Yao Chang Chen, Yu-Hsun Kao, Yen Yu Lu, Yung-Kuo Lin, Shih A. Chen, Yi-Jen Chen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Aging and testosterone deficiency contribute to the pathogenesis of atrial fibrillation (AF). We determine the effects of testosterone replacement on the electrophysiology and arrhythmogenesis of pulmonary vein (PV) and left atrium (LA) in aged rabbits. Methods Electrocardiography, heart rate variability, echocardiography, Western blot and conventional microelectrodes were used in aged rabbits (age, > 2 years) with and without (control) testosterone treatment (10 mg/kg, 12 weeks). Results Testosterone-treated aged rabbits had longer corrected QT interval, higher low frequency/high frequency, greater left ventricle (LV) mass but lower LA total emptying fraction and LV ejection fraction than control rabbits. In tissue preparations, the spontaneous rate was faster for testosterone-treated PVs than for control PVs. Angiotensin II concentration-dependently increased the amplitude of delayed afterdepolarizations (DADs) in testosterone-treated PVs but only did so at the highest angiotensin II concentration (100 nM) in control PVs. Isoproterenol increased the incidence of early afterdepolarizations (EADs) and DADs in testosterone-treated PVs but not in control PVs. Testosterone-treated PVs had more H2O2-induced burst firing and EADs than control PVs. Testosterone-treated LAs had more isoproterenol-induced DADs and spontaneous activity than did control LAs. However, acetylcholine infusion and rapid atrial pacing (10-20 Hz) induced AF in control LAs but not in testosterone-treated LAs. In addition, as compared with control LAs, testosterone-treated LAs expressed more androgen receptor, β1-adrenergic receptor, and Cav 1.2 and less G protein-coupled receptor kinase-2 and Kv 4.2. Conclusions Testosterone replacement increased arrhythmogenesis in PV and LA by enhancing adrenergic activity in aged rabbits.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalInternational Journal of Cardiology
Volume176
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Pulmonary Veins
Heart Atria
Adrenergic Agents
Testosterone
Rabbits
Isoproterenol
Angiotensin II
Atrial Fibrillation
Heart Ventricles
G-Protein-Coupled Receptor Kinase 2
Electrophysiology
Androgen Receptors
Microelectrodes
Adrenergic Receptors
Acetylcholine
Echocardiography
Electrocardiography
Heart Rate
Western Blotting

Keywords

  • Adrenergic activity
  • Atrial fibrillation
  • Pulmonary vein
  • Testosterone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Testosterone replacement increases aged pulmonary vein and left atrium arrhythmogenesis with enhanced adrenergic activity. / Tsai, Wen Chin; Lee, Ting-I; Chen, Yao Chang; Kao, Yu-Hsun; Lu, Yen Yu; Lin, Yung-Kuo; Chen, Shih A.; Chen, Yi-Jen.

In: International Journal of Cardiology, Vol. 176, No. 1, 2014, p. 110-118.

Research output: Contribution to journalArticle

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abstract = "Background Aging and testosterone deficiency contribute to the pathogenesis of atrial fibrillation (AF). We determine the effects of testosterone replacement on the electrophysiology and arrhythmogenesis of pulmonary vein (PV) and left atrium (LA) in aged rabbits. Methods Electrocardiography, heart rate variability, echocardiography, Western blot and conventional microelectrodes were used in aged rabbits (age, > 2 years) with and without (control) testosterone treatment (10 mg/kg, 12 weeks). Results Testosterone-treated aged rabbits had longer corrected QT interval, higher low frequency/high frequency, greater left ventricle (LV) mass but lower LA total emptying fraction and LV ejection fraction than control rabbits. In tissue preparations, the spontaneous rate was faster for testosterone-treated PVs than for control PVs. Angiotensin II concentration-dependently increased the amplitude of delayed afterdepolarizations (DADs) in testosterone-treated PVs but only did so at the highest angiotensin II concentration (100 nM) in control PVs. Isoproterenol increased the incidence of early afterdepolarizations (EADs) and DADs in testosterone-treated PVs but not in control PVs. Testosterone-treated PVs had more H2O2-induced burst firing and EADs than control PVs. Testosterone-treated LAs had more isoproterenol-induced DADs and spontaneous activity than did control LAs. However, acetylcholine infusion and rapid atrial pacing (10-20 Hz) induced AF in control LAs but not in testosterone-treated LAs. In addition, as compared with control LAs, testosterone-treated LAs expressed more androgen receptor, β1-adrenergic receptor, and Cav 1.2 and less G protein-coupled receptor kinase-2 and Kv 4.2. Conclusions Testosterone replacement increased arrhythmogenesis in PV and LA by enhancing adrenergic activity in aged rabbits.",
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AB - Background Aging and testosterone deficiency contribute to the pathogenesis of atrial fibrillation (AF). We determine the effects of testosterone replacement on the electrophysiology and arrhythmogenesis of pulmonary vein (PV) and left atrium (LA) in aged rabbits. Methods Electrocardiography, heart rate variability, echocardiography, Western blot and conventional microelectrodes were used in aged rabbits (age, > 2 years) with and without (control) testosterone treatment (10 mg/kg, 12 weeks). Results Testosterone-treated aged rabbits had longer corrected QT interval, higher low frequency/high frequency, greater left ventricle (LV) mass but lower LA total emptying fraction and LV ejection fraction than control rabbits. In tissue preparations, the spontaneous rate was faster for testosterone-treated PVs than for control PVs. Angiotensin II concentration-dependently increased the amplitude of delayed afterdepolarizations (DADs) in testosterone-treated PVs but only did so at the highest angiotensin II concentration (100 nM) in control PVs. Isoproterenol increased the incidence of early afterdepolarizations (EADs) and DADs in testosterone-treated PVs but not in control PVs. Testosterone-treated PVs had more H2O2-induced burst firing and EADs than control PVs. Testosterone-treated LAs had more isoproterenol-induced DADs and spontaneous activity than did control LAs. However, acetylcholine infusion and rapid atrial pacing (10-20 Hz) induced AF in control LAs but not in testosterone-treated LAs. In addition, as compared with control LAs, testosterone-treated LAs expressed more androgen receptor, β1-adrenergic receptor, and Cav 1.2 and less G protein-coupled receptor kinase-2 and Kv 4.2. Conclusions Testosterone replacement increased arrhythmogenesis in PV and LA by enhancing adrenergic activity in aged rabbits.

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