Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation.
Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation.
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DOI：
10.1093/cvr/cvaa162
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发表时间：
2021-06-16
影响因子：
10.8
通讯作者：
Voigt N
中科院分区：
文献类型：
--
作者：
Fakuade FE;Steckmeister V;Seibertz F;Gronwald J;Kestel S;Menzel J;Pronto JRD;Taha K;Haghighi F;Kensah G;Pearman CM;Wiedmann F;Teske AJ;Schmidt C;Dibb KM;El-Essawi A;Danner BC;Baraki H;Schwappach B;Kutschka I;Mason FE;Voigt N
心房颤动 (AF) 是心脏手术后常见的心律失常（术后 AF，poAF），与较差的预后相关。考虑到心房收缩功能降低是 poAF 的预测因子，并且 Ca2+ 在兴奋-收缩耦合和房性心律失常发生中发挥重要作用，本研究旨在测试细胞内 Ca2+ 处理的改变是否会导致心房收缩力受损以及导致患者易患 poAF 的心律失常底物。右心耳取自接受心脏直视手术的窦性心律患者。通过同时测量 [Ca2+]i 和动作电位（AP、膜片钳）来研究心肌细胞。对患者进行 6 天的随访，以确定患有或不患有 poAF 的患者。术前超声心动图斑点追踪分析显示 POAF 患者左心房收缩应变减少。手术时，poAF 组的细胞 Ca2+ 瞬变 (CaTs) 和肌浆网 (SR) Ca2+ 含量较小。 poAF 中的 CaT 衰减较慢，但咖啡因诱导的 Ca2+ 瞬变的衰减没有改变，表明钠钙交换功能得以保留。与此一致的是，蛋白质印迹显示 POAF 患者 SERCA2a 表达减少，但受磷蛋白表达/磷酸化未改变。计算模型表明 SERCA 活性降低会促进 CaT 和 AP 交替的发生。事实上，POAF 患者的心房肌细胞中 CaT 和 AP 的交替发生更频繁且刺激频率更低。两组在不同起搏频率（0.25–8Hz）下的静息膜电位和 AP 持续时间相当。生化、功能和建模数据表明，SERCA 介导的 SR 中 Ca2+ 再摄取减少是导致术前心房收缩功能受损以及发生 poAF 的患者预先存在的致心律失常底物的主要原因。
Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation–contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF. Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25–8 Hz). Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF.
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影响因子：
64.8
作者：
Kho, Changwon;Lee, Ahyoung;Jeong, Dongtak;Oh, Jae Gyun;Chaanine, Antoine H.;Kizana, Eddy;Park, Woo Jin;Hajjar, Roger J.
通讯作者：
Hajjar, Roger J.
影响因子：
9
作者：
LOWE, JE;HENDRY, PJ;WELLS, R
通讯作者：
WELLS, R
DOI：
10.1016/j.bbrc.2007.03.124
发表时间：
2007-05-25
影响因子：
3.1
作者：
Lezoualc'h, Frank;Steplewski, Klaudia;Bril, Antoine
通讯作者：
Bril, Antoine
DOI：
10.1093/europace/eur208
发表时间：
2012-02
期刊：
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
影响因子：
--
作者：
Maesen B;Nijs J;Maessen J;Allessie M;Schotten U
通讯作者：
Schotten U
DOI：
10.1152/ajpheart.00384.2012
发表时间：
2012-10-01
影响因子：
4.8
作者：
Florea, Stela M.;Blatter, Lothar A.
通讯作者：
Blatter, Lothar A.