Division of Cardiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Transl Res. 2018 Oct;200:54-64. doi: 10.1016/j.trsl.2018.06.002. Epub 2018 Jun 14.
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. HO 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% (APD) 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.
心脏手术伴有心房颤动（AF）。组蛋白去乙酰化酶（HDAC）抑制可减少 AF 的发生。在心包炎中，HDAC 抑制可能调节 AF 触发和底物。我们在对照组和心包切开术（op）兔子中记录心电图，这些兔子没有接受腹腔注射 MPT0E014（HDAC 抑制剂）和接受了腹腔注射 MPT0E014。常规微电极记录肺静脉（PVs）、右心房（LA）和左心房（LA）的动作电位（APs）。Masson 三色法用于识别 PVs 和 LA 中的胶原纤维。心电图显示 op 兔子中频繁出现房性期前收缩，但在其他 3 组中没有。MPT0E014 处理后，PVs 和 opPVs 的搏动率降低。在 opPVs 中发生自发性爆发性放电（36.4%），但在对照 PVs 中没有。HO 在 opPVs 中引起的爆发性放电（72.7%）大于对照 PVs（11.1%）、MPT0E014 处理的 PVs（16.7%）和 MPT0E014 处理的 opPVs（12.5%）。opLA 的复极化程度为 90%时的动作电位时程（APD）短于对照 LA。在存在异丙肾上腺素（1 μM）的情况下，快速心房起搏（RAP，20 Hz）在 opLA 中引起爆发性放电的发生率高于其他组（90%）。相反，乙酰胆碱（5 mM）和 RAP 在 MPT0E014 处理的 LA 中引起爆发性放电的发生率低于其他组（33.3%）。与相应的对照 PVs 和 LA 相比，opPVs 和 opLA 中普遍存在纤维化，而接受 MPT0E014 治疗的纤维化程度减轻。结论：心包切开术增加了 PVs 和 LA 中的纤维化和心律失常发生，而 HDAC 抑制可预防这种情况。
