Histone deacetylase inhibition attenuates atrial arrhythmogenesis in sterile pericarditis

Autor: Shao Jung Li, Yi Jen Chen, Yao Chang Chen, Shih Yu Huang, Chien Jung Chang, Shih Ann Chen
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Indoles
medicine.medical_treatment
Intraperitoneal injection
Action Potentials
030204 cardiovascular system & hematology
Hydroxamic Acids
Electrocardiography
03 medical and health sciences
Pericarditis
0302 clinical medicine
Fibrosis
Physiology (medical)
Internal medicine
Atrial Fibrillation
medicine
Animals
Repolarization
Heart Atria
medicine.diagnostic_test
business.industry
Biochemistry (medical)
Isoproterenol
Public Health
Environmental and Occupational Health
Atrial fibrillation
Hydrogen Peroxide
General Medicine
medicine.disease
Acetylcholine
Histone Deacetylase Inhibitors
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Pulmonary Veins
cardiovascular system
Cardiology
Collagen
Rabbits
Histone deacetylase
business
Microelectrodes
Injections
Intraperitoneal
medicine.drug
Zdroj: Translational Research. 200:54-64
ISSN: 1931-5244
DOI: 10.1016/j.trsl.2018.06.002
Popis: 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.
Databáze: OpenAIRE
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