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巨大T波电交替(macro-TWA)是指T波振幅、宽度、形态甚至极性在恒定频率下出现逐搏交替变化，且在ECG的全部12导联或大部分导联中均清晰可见，其常发生在有明显QT间期延长的情况下，如先天性或获得性QT综合征，但巨大T波电交替引起心律失常发生的离子和细胞机制尚不清楚。齐大屯等采用肾血管性高血压模型诱导家兔左室肥厚模型。同时记录兔左心室灌注楔形模型的心外膜和心内膜的动作电位、透壁ECG和等长收缩力。用全细胞膜片钳技术记录左室心肌细胞的晚期钠电流(INa-L)。发现：左室肥厚使INa-L密度增加，促进左室心内膜早后除极电交替，表现为macro-TWA和不协调的机械性交替。阻断INa-L消除了macro-TWA、机械性交替、早后除极依赖的R-from-T早搏和尖端扭转型室速。
中国医学科学院阜外医院华中医院齐大屯博士在Circulation （子刊Arrythmia Electrophysiol. 2023;16:e0 11453/CIRCEP.122.011453）发表原创论文：用全细胞膜片钳及楔形组织块技术验证左室心肌肥厚可导致心肌细胞晚期钠电流(INa-L)增加，应用阻滞剂雷诺嗪或美西律可有效阻滞Macro-TWA、机械性交替、R-from-T早搏和TdP的发生，揭示了T波电交替的潜在机制。
既往认为，T波电交替是缓慢激活延迟整流钾电流及钙通道异常介导。在临床工作中，齐大屯等对T波电交替的电生理机制充满好奇。一位73岁肥厚型心肌病女性患者，住院期间发现频发室早合并巨大T波电交替，给予“美西律”药物治疗，患者的早搏及T波电交替消失，再出现类似患者时，同样的治疗方法仍然有效，“美西律”作为抗心律失常药物，可以抑制晚钠电流，是否晚钠电流就是该患者出现巨大T波电交替及早搏的启动因素。经过膜片钳及楔形组织块技术验证，我们团队认为晚钠电流的增强会导致巨大T波电交替，而阻断晚钠电流会抑制该现象，从而证实巨大T波电交替产生的离子流基础可能是晚钠电流增加导致。
Macroscopic T Wave Alternans means that the amplitude, width, shape and even polarity of T wave changes from beat to beat at a constant frequency, and can be clearly seen in all 12 leads or most of the leads of ECG. It often occurs in obvious QT interval extension, such as congenital or acquired QT syndrome. The left ventricular hypertrophy model of rabbits were acquired by renovascular hypertension model. The Action potential, transmural ECG and isometric contractility of epicardium and endocardium of rabbit left ventricular perfusion wedge model was also recorded. The late sodium current (INa-L) of left ventricular myocytes were recorded by whole cell Patch clamp. It was found that left ventricular hypertrophy increased the density of INa-L, and promoted the electrical alternation of early and late depolarization of left ventricular endocardium, which was characterized by macro TWA and uncoordinated mechanical alternation. Blocking INa-L eliminated macro TWA, mechanical alternation, and early post depolarization dependent R-from T premature beats and TDP.
Circulation (arrythmia Electrophysiology)2023; 16: e011453/CIRCEP. 122.011453)published an original paper finished by Dr.Qidatun: using whole cell Patch clamp and wedge tissue technology to verify that left ventricular hypertrophy can lead to the increase of late sodium current (INa-L) in myocardial cells, and the application of the blocker ranolazine or Mexiletine can effectively block the occurrence of Macro-TWA, mechanical alternation, R-from-T premature beat and TdP, Revealed the potential mechanism of T-wave alternation.
It was previously believed that T-wave alternation was mediated by slowly activating delayed rectifier potassium current and abnormal Calcium channel. In clinical work,Dr.Qi Datun are curious about the electrophysiological mechanism of T-wave alternation.Frequent ventricular premature beats combined with Macroscopic T Wave alternations were found in a 73-year-old female patient with hypertrophic cardiomyopathy. Mexiletine was given to treat the patient. The patient's premature beats and T-wave altercations disappeared.The same treatment method remain effective in similar patients. We all know that, as an antiarrhythmic drug, Mexiletine can inhibit the late sodium current (INa-L). Whether the late sodium current is the initiating factor for the occurrence of macro TWA and premature beats in this patient? After Patch clamp and wedge tissue technology verification, our team find that the enhancement of late sodium current will lead to macro TWA, and blocking the late sodium current will inhibit this phenomenon.
Datun Qi, Wei Li, Xiao-Qing Quan, et al.Alternating Early Afterdepolarizations Underlying Bradycardia-Dependent Macroscopic T Wave and Discordant Mechanical Alternans.Circulation: Arrhythmia and Electrophysiology,Volume 16, Issue 11 January 2023
齐大屯，医学博士，副主任医师，硕士研究生导师,河南省医学会心血管病分会青年委员会副主任委员,河南省心电一张网工作委员会委员,2014年美国Lankenau医院访问学者,2019年英国帝国理工学院附属Hammersmith医院访问学者,专业方向：心血管内科,主要从事冠心病的诊断与治疗工作，心律失常的电生理基础及药物治疗工作。主持国家自然科学基金1项，参与国家自然科学基金2项。作为术者，完成了河南省第一例Impella支持下心肌梗死患者的救治。
邮箱：qimedicine@zzu.edu.cn
Datun Qi, doctor of medicine, associate chief physician, supervisor of postgraduate
Deputy chairman of youth committee of cardiovascular branch of Henan medical association
Member of Henan province electrocardiogram net work committee In 2014, the academic visitor of Lankenau hospital, PA, U.S.A
In 2019, the academic visitor of Hammersmith Hospital, Imperial College London, UK Professional direction: cardiovascular disease
Engaged in the diagnosis and treatment of coronary heart disease,and the electrophysiological basis of arrhythmia. Hosted one project of the National Natural Science Foundation of China and participated in two projects of the National Natural Science Foundation of China.
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