Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis

Chien Jung Chang, Shao Jung Li, Yao Chang Chen, Shih Yu Huang, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

Abstract

Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4%), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7%) than in control PVs (11.1%), MPT0E014-treated PVs (16.7%), and MPT0E014-treated opPVs (12.5%). The AP duration at a repolarization extent of 90% (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 μM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90%) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3%) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.

Original languageEnglish
JournalTranslational Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Histone Deacetylases
Pericarditis
Pulmonary Veins
Heart Atria
Atrial Fibrillation
Electrocardiography
Action Potentials
Histone Deacetylase Inhibitors
Fibrosis
Microelectrodes
Atrial Premature Complexes
Pericardiectomy
Rabbits
Isoproterenol
Surgery
Acetylcholine
3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide
Incidence
Collagen
Intraperitoneal Injections

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical

Cite this

Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis. / Chang, Chien Jung; Li, Shao Jung; Chen, Yao Chang; Huang, Shih Yu; Chen, Shih Ann; Chen, Yi Jen.

In: Translational Research, 01.01.2018.

Research output: Contribution to journalArticle

Chang, Chien Jung ; Li, Shao Jung ; Chen, Yao Chang ; Huang, Shih Yu ; Chen, Shih Ann ; Chen, Yi Jen. / Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis. In: Translational Research. 2018.
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abstract = "Cardiac surgery is complicated with atrial fibrillation (AF). Histone deacetylase (HDAC) inhibition reduces AF occurrence. In pericarditis, HDAC inhibition may modulate AF trigger and substrate. We recorded electrocardiograms in control and pericardiotomic (op) rabbits without and with an intraperitoneal injection of MPT0E014 (HDAC inhibitor). Conventional microelectrodes recorded action potentials (APs) in pulmonary veins (PVs), the right and left atrium (LA). Masson's trichrome was used to identify collagen fibers in PVs and the LA. Electrocardiograms showed frequent atrial premature contractions in op rabbits, but not in the other 3 groups. The beating rates in PVs and opPVs were decreased by MPT0E014 treatment. Spontaneous burst firings occurred in opPVs (36.4{\%}), but not in control PVs. H2O2 induced greater burst firings in opPVs (72.7{\%}) than in control PVs (11.1{\%}), MPT0E014-treated PVs (16.7{\%}), and MPT0E014-treated opPVs (12.5{\%}). The AP duration at a repolarization extent of 90{\%} (APD90) was shorter in the opLA than that in the control LA. In the presence of isoproterenol (1 μM), rapid atrial pacing (RAP, 20 Hz) induced a higher incidence of burst firings in the opLA (90{\%}) than in the other groups. In contrast, acetylcholine (5 mM) and RAP induced a lower incidence of burst firing in the MPT0E014-treated LA (33.3{\%}) than in the other groups. Fibrosis prevailed in opPVs and the opLA compared to the respective control PVs and LA, which was attenuated in those that received MPT0E014. In conclusion, a pericardiotomy increased fibrosis and arrhythmogenesis in PVs and the LA, which were prevented by HDAC inhibition.",
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