Ionic mechanisms underlying atrial electrical remodeling after a fontan-style operation in a canine model
Ionic mechanisms underlying atrial electrical remodeling after a fontan-style operation in a canine model
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犬模型中 Fontan 式手术后心房电重塑的离子机制
DOI：
10.1007/s00380-019-01544-5
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发表时间：
2020-05-01
影响因子：
1.5
通讯作者：
Li, Fen
中科院分区：
文献类型：
--
作者：
Wu, Jinjin;Zhou, Wanping;Li, Fen
房性心律失常是方丹式手术后患者晚期死亡的重要原因。然而，fontan后心房的详细电生理特征及其潜在机制在很大程度上是未知的。本研究研究了Fontan手术后犬右心房的电生理特征和离子重构。我们采用RA与肺动脉连接的手术来模拟Fontan手术。我们进行了血流动力学测量、心脏电生理研究和离子电流测量。采用PCR和western-blotting分析离子通道的表达。我们的Fontan模型诱导RA高血压，RA大小增大，心房纤维化增加，代表了Fontan患者的经典特征。方丹组心房有效不应期和活动电位持续时间缩短，诱发心房心动过速的次数增多。电导图显示，方丹组降低了传导速度。Fontan操作显著下调KCND3/Kv4.3、CACNA1C/Cav1.2和SCN5A的表达，上调KCNJ2/Kir2.1的表达。相应地，Fontan操作减少了瞬态外向（I-to）和l型Ca2 （I-Ca,I-L）和I-Na电流，同时增加了内向整流电流（I-K1）。因此，fontan后心房动作电位的净缩短与离子通道表达的改变有关，离子通道的表达破坏了内向和外向电流之间的平衡。综上所述，Fontan手术诱导了离子重构，从而改变了右心房的电生理特征，提高了我们对Fontan患者心房心律失常病理生理的认识。
Atrial arrhythmia is an important cause of late death in patients after the Fontan-Style operation. However, the detailed electrophysiological characteristics of the post-Fontan atrium and its underlying mechanisms are largely unknown. In this study, we investigated electrophysiological characteristics and the ionic remodeling in the right atrium (RA) of a canine model after the Fontan operation. We performed the operation of RA to pulmonary artery connection to mimic the Fontan operation. We undertook hemodynamic measurements, cardiac electrophysiological studies, and ion current measurements. The expression of ionic channels was analyzed by PCR and western-blotting. Our Fontan model induced RA hypertension, enlarged the size of RA, and increased atrial fibrosis, representing the classic characteristic of Fontan patients. In the Fontan group, the atrial effective refractory period and the active potential duration were reduced, and the atrial tachycardia has been more often to be induced. The electrical conduction mapping showed that the Fontan group reduced the conduction velocity. The Fontan operation significantly down-regulated the expression of KCND3/Kv4.3, CACNA1C/Cav1.2 and SCN5A, but up-regulated the expression of KCNJ2/Kir2.1. Correspondingly, The Fontan operation reduced transient-outward (I-to) and L-type Ca2 (I-Ca,I-L) and I-Na currents, while increasing the inward-rectifier current (I-K1). Thus, the net shortening of the action potential in the post-Fontan atrium is associated with the altered expression of ionic channels which disturbed the balance between inward and outward currents. Taken together, the Fontan operation induces the ionic remodeling, and thus altered electrophysiological characteristics of the right atrium, improving our understanding on the pathophysiology of atrial arrhythmias in Fontan patients.