术后心房颤动发病机制的研究进展

betway必威登陆网址（betway.com ）学报››2022,Vol. 43››Issue (12): 891-896.DOI:10.3969/j.issn.2097-0005.2022.12.003

术后心房颤动发病机制的研究进展

廖杰¹(), 杜以梅²()

^1.四川省医学科学院/四川省人民医院心内科, 四川成都 610072
^2.华中科技大学同济医学院附属协和医院心内科, 湖北武汉 430022

收稿日期:2022-10-16出版日期:2022-12-25发布日期:2023-02-08
通讯作者:杜以梅
作者简介:廖杰，博士，住院医师，研究方向：心脏电生理、心律失常临床及基础，E-mail：1337053260@qq.com。
杜以梅，理学博士，美国博士后，博士生导师，华中科技大学同济医学院附属协和医院心内科教授，协和医院离子通道病研究中心副主任。湖北省暨武汉生理学会副理事长，中国生理学会委员，国际生物物理学会会员。国家自然科学基金、省自然科学基金、英国Welcome Trust基金评审专家。先后担任《临床心血管病杂志》常务编委， Scientific Reports、 Cardiovascular Diagnosis and Therapy、 Frontiers in Cell and Developmental Biology等杂志学术编辑，多个SCI杂志特约审稿人。主要从事心脏电生理和心血管免疫学研究，主持国家自然科学基金面上项目5项，作为主要骨干参加国家973项目子课题1项及国家自然科学基金重点项目1项，以第一或通讯作者发表论文60余篇。
基金资助:
国家自然科学基金(82170326);四川省自然科学基金(2022NSFSC1589)

Advances in the pathogenesis of postoperative atrial fibrillation

Jie LIAO¹(), Yimei DU²()

^1.Department of Cardiology，Sichuan Provincial People's Hospital，University of Electronic Science and Technology of China； Department of Cardiology，Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital，Chengdu 610072，China
^2.Department of Cardiology，Union Hospital，Tongji Medical College，Huazhong University of Science and Technology，Wuhan 430022，China

Received:2022-10-16Online:2022-12-25Published:2023-02-08
Contact:Yimei DU

摘要/Abstract

摘要：

术后心房颤动（postoperative atrial fibrillation， POAF）是心脏外科手术后常见的并发症，发病率为20% ~ 40%，术后第2 ~ 4天高发，以短暂发作和自限性为疾病特征。POAF可能导致血流动力学不稳定及增加中风风险，从而增加患者住院时间和费用；且近期的观察性队列研究表明，心脏瓣膜手术后发生POAF的患者远期血栓栓塞风险仍然很大。大量的研究表明，心房炎症是POAF发病的中心环节，与其相关的电重构、钙稳态失衡、纤维化、氧化应激和/或自主神经激活共同参与并促进POAF的发作。结合本课题组的一系列研究成果，本文对POAF的发病机制进行综述。

关键词:术后心房颤动,发病机制,心房炎症

Abstract:

Postoperative atrial fibrillation （POAF） is a common complication of cardiac surgery， with an incidence of 20% ~ 40%. Typical features include onset mostly at 2 ~ 4 days after surgery， fleeting episode， and self-limitation. POAF may cause hemodynamic instability and increase the risk of stroke， thus increasing the length and cost of stay in hospital. In addition， a recent observational cohort study has suggested that patients who developed POAF after cardiac valve surgery still has a great long-term risk of thromboembolism. A series of studies have shown that atrial inflammation is the central link in the pathogenesis of POAF， and its related electrical remodeling， calcium handling abnormalities， fibrosis， oxidative stress， and/orautonomic nervous system activation jointly promote the onset of POAF. Combined with a series of results of our research group， the proarrhythmic mechanisms of POAF are discussed in this review.

Key words:POAF,mechanisms,atrial inflammation

廖杰, 杜以梅. 术后心房颤动发病机制的研究进展[J]. betway必威登陆网址（betway.com ）学报, 2022, 43(12): 891-896.

Jie LIAO, Yimei DU. Advances in the pathogenesis of postoperative atrial fibrillation[J]. Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences, 2022, 43(12): 891-896.

图/表1

参考文献42

1	Dobrev D， Aguilar M， Heijman J， et al. Postoperative atrial fibrillation： mechanisms， manifestations and management［J］. Nat Rev Cardiol， 2019， 16（7）： 417.
2	Butt JH， Olesen JB， Gundlund A， et al. Long-term thromboembolic risk in patients with postoperative atrial fibrillation after left-sided heart valve surgery［J］. JAMA Cardiol， 2019， 4（11）： 1139.
3	Butt JH， Xian Y， Peterson ED， et al. Long-term thromboembolic risk in patients with postoperative atrial fibrillation after coronary artery bypass graft surgery and patients with nonvalvular atrial fibrillation［J］. JAMA Cardiol， 2018， 3（5）： 417.
4	Dobrev D， Heijman J， Hiram R， et al. Inflammatory signalling in atrial cardiomyocytes： a novel unifying principle in atrial fibrillation pathophysiology［J/OL］. Nat Rev Cardiol. （2022-09-15）. . DOI：10.1038/s41569-022-00759-w.
5	Nishida K， Michael G， Dobrev D， et al. Animal models for atrial fibrillation： clinical insights and scientific opportunities［J］. Europace， 2010， 12（2）： 160.
6	Fu XX， Zhao N， Dong Q， et al. Interleukin-17a contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis［J］. Int J Mol Med， 2015， 36（1）： 83.
7	Zhang Z， Zhang C， Wang H， et al. n-3 polyunsaturated fatty acids prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model［J］. Int J Cardiol， 2011， 153（1）： 14.
8	Yang S， Zhao Z， Zhao N， et al. Blockage of transient receptor potential vanilloid 4 prevents postoperative atrial fibrillation by inhibiting NLRP3-inflammasome in sterile pericarditis mice［J］. Cell Calcium， 2022， 104： 102590.
9	Gaudino M， Di Franco A， Rong LQ， et al. Pericardial effusion provoking atrial fibrillation after cardiac surgery： JACC review topic of the week［J］. J Am Coll Cardiol， 2022， 79（25）： 2529.
10	Gudbjartsson T， Helgadottir S， Sigurdsson MI， et al. New-onset postoperative atrial fibrillation after heart surgery［J］. Acta Anaesthesiol Scand， 2020， 64（2）： 145.
11	Liao J， Wu Q， Qian C， et al. TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats［J］. JCI Insight， 2020， 5（23）： e137528.
12	Liao J， Zhang S， Yang S， et al. Interleukin-6-mediated-Ca²⁺handling abnormalities contributes to atrial fibrillation in sterile pericarditis rats［J］. Front Immunol， 2021， 12： 758157.
13	Kumagai K， Nakashima H， Saku K. The HMG-CoA reductase inhibitor atorvastatin prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model［J］. Cardiovasc Res， 2004， 62（1）： 105.
14	Ryu K， Li L， Khrestian CM， et al. Effects of sterile pericarditis on connexins 40 and 43 in the atria： correlation with abnormal conduction and atrial arrhythmias［J］. Am J Physiol Heart Circ Physiol， 2007， 293（2）： H1231.
15	Kulkarni K， Merchant FM， Kassab MB， et al. Cardiac alternans： mechanisms and clinical utility in arrhythmia prevention［J］. J Am Heart Assoc， 2019， 8（21）： e013750.
16	Escobar AL， Valdivia HH. Cardiac alternans and ventricular fibrillation： a bad case of ryanodine receptors reneging on their duty［J］. Circ Res， 2014， 114（9）： 1369.
17	Monnerat G， Alarcón ML， Vasconcellos LR， et al. Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice［J］. Nat Commun， 2016， 7： 13344.
18	Mitrokhin VM， Mladenov MI， Kamkin AG. Effects of interleukin-6 on the bio-electric activity of rat atrial tissue under normal conditions and during gradual stretching［J］. Immunobiology， 2015， 220（9）： 1107.
19	Nishida K， Datino T， Macle L， et al. Atrial fibrillation ablation： translating basic mechanistic insights to the patient［J］. J Am Coll Cardiol， 2014， 64（8）： 823.
20	Bers DM. Cardiac excitation-contraction coupling［J］. Nature， 2002， 415（6868）： 198.
21	廖杰，杨帅涛，卢凯，等. 口服TRPV4抑制剂改善无菌性心包炎大鼠心房钙稳态失衡［J］. 生理学报， 2022， 74（2）： 188.
22	Fernández-Sada E， Torres-Quintanilla A， Silva-Platas C， et al. Proinflammatory cytokines are soluble mediators linked with ventricular arrhythmias and contractile dysfunction in a rat model of metabolic syndrome［J］. Oxid Med Cell Longev， 2017， 2017： 7682569.
23	El Khoury N， Mathieu S， Fiset C. Interleukin-1β reduces L-type Ca²⁺current through protein kinase Cϵ activation in mouse heart［J］. J Biol Chem， 2014， 289（32）： 21896.
24	De Jesus NM， Wang L， Lai J， et al. Antiarrhythmic effects of interleukin 1 inhibition after myocardial infarction［J］. Heart Rhythm， 2017， 14（5）： 727.
25	Heijman J， Muna AP， Veleva T， et al. Atrial myocyte NLRP3/CaMKII nexus forms a substrate for postoperative atrial fibrillation［J］. Circ Res， 2020， 127（8）： 1036.
26	Huang Z， Chen XJ， Qian C， et al. Signal transducer and activator of transcription 3/MicroRNA-21 feedback loop contributes to atrial fibrillation by promoting atrial fibrosis in a rat sterile pericarditis model［J］. Circ Arrhythm Electrophysiol， 2016， 9（7）： e003396.
27	Liu Y， Wu F， Wu Y， et al. Mechanism of IL-6-related spontaneous atrial fibrillation after coronary artery grafting surgery： IL-6 knockout mouse study and human observation［J］. Transl Res， 2021， 233： 16.
28	Wu Q， Liu H， Liao J， et al. Colchicine prevents atrial fibrillation promotion by inhibiting IL-1β-induced IL-6 release and atrial fibrosis in the rat sterile pericarditis model［J］. Biomed Pharmacother， 2020， 129： 110384.
29	Simon JN， Ziberna K， Casadei B. Compromised redox homeostasis， altered nitroso-redox balance， and therapeutic possibilities in atrial fibrillation［J］. Cardiovasc Res， 2016， 109（4）： 510.
30	Purohit A， Rokita AG， Guan X， et al. Oxidized Ca²⁺/calmodulin-dependent protein kinase Ⅱ triggers atrial fibrillation［J］. Circulation， 2013， 128（16）： 1748.
31	Yeh YH， Hsu LA， Chen YH， et al. Protective role of heme oxygenase-1 in atrial remodeling［J］. Basic Res Cardiol， 2016， 111（5）： 58.
32	McCauley MD， Hong L， Sridhar A， et al. Ion channel and structural remodeling in obesity-mediated atrial fibrillation［J］. Circ Arrhythm Electrophysiol， 2020， 13（8）： e008296.
33	Yang X， An N， Zhong C， et al. Enhanced cardiomyocyte reactive oxygen species signaling promotes ibrutinib-induced atrial fibrillation［J］. Redox Biol， 2020， 30： 101432.
34	Anderson EJ， Efird JT， Davies SW， et al. Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation［J］. J Am Heart Assoc， 2014， 3（1）： e000713.
35	Reilly SN， Jayaram R， Nahar K， et al. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation： implications for the antiarrhythmic effect of statins［J］. Circulation， 2011， 124（10）： 1107.
36	Zuo S， Li LL， Ruan YF， et al. Acute administration of tumour necrosis factor-α induces spontaneous calcium release via the reactive oxygen species pathway in atrial myocytes［J］. Europace， 2018， 20（8）： 1367.
37	Rudolph V， Andrié RP， Rudolph TK， et al. Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation［J］. Nat Med， 2010， 16（4）： 470.
38	Chen PS， Chen LS， Fishbein MC， et al. Role of the autonomic nervous system in atrial fibrillation： pathophysiology and therapy［J］. Circ Res， 2014， 114（9）： 1500.
39	Anderson EJ， Efird JT， Kiser AC， et al. Plasma catecholamine levels on the morning of surgery predict post-operative atrial fibrillation［J］. JACC Clin Electrophysiol， 2017， 3（12）： 1456.
40	O'Quinn MP， Dormer KJ， Huizar JF， et al. Epicardial injection of nanoformulated calcium into cardiac ganglionic plexi suppresses autonomic nerve activity and postoperative atrial fibrillation［J］. Heart Rhythm， 2019， 16（4）： 597.
41	Stavrakis S， Humphrey MB， Scherlag B， et al. Low-level vagus nerve stimulation suppresses post-operative atrial fibrillation and inflammation： a randomized study［J］. JACC Clin Electrophysiol， 2017， 3（9）： 929.
42	Andreas M， Arzl P， Mitterbauer A， et al. Electrical stimulation of the greater auricular nerve to reduce postoperative atrial fibrillation［J］. Circ Arrhythm Electrophysiol， 2019， 12（10）： e007711.

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