缺血性心脏病是严重危害人类健康的主要疾病之一。急性心肌缺血时心电图上新出现的J波是室速/室颤及心源性猝死的高危预警信号。J波的产生与心脏离子通道功能改变引起的净外向电流增加有关。单倍体不足基因突变是基因突变改变离子通道功能的主要原因之一，也是携带基因突变的隐匿性患者发生获得性心律失常的一个重要危险因素。课题组前期研究显示，携带突变基因是获得性长QT综合征及心源性猝死发生的危险因素。然而，单倍体不足基因突变是否为急性缺血性J波的危险因素，尚未报道。本研究拟采用SCN5A基因敲除的杂合子小鼠动物模型，模拟单倍体不足基因突变，通过建立该小鼠冠状动脉灌注楔形组织块的缺血模型，利用浮置玻璃微电极和心电图同步记录及全细胞膜片钳技术，观察组织块和分离的心肌细胞的电生理特性，探索单倍体不足基因突变是否为缺血性J波的危险因素；并进行药物干预研究，为缺血性J波综合征的临床管理提供实验依据。

Ischemic heart disease (IHD) is a major cause of death both in China and worldwide. As well as heart failure, the main symptoms of IHD are chest pain and ventricular tachycardia especially torsades de pointes (TdP), the main cause of sudden cardiac death (SCD). The J wave is a distinctive deflection occurring at the QRS-ST junction on 12 lead electrogram, and it was regarded as one of most crucial risk factors of SCD in patients with acute myocardial infarction. It is reported that the mechanisms of J wave are linked to abnormalities in the manifestation of the transient outward current (Ito). Besides, Haploinsufficiency gene, which is one of the mechanisms cause cardiac ion channel dysfunction, is considered as a major cause of secondary cardiac arrhythmia. Based on our previous research and observation, A561V‑hERG gene mutation result in decreased hERG currents and impairment of hERG membrane localization, showing a prolonged QT interval and tendency of TdP clinically. However, the potential of haploinsufficiency SCN5A gene mutation on ischemic induced J wave has not been reported. Therefore, in the present study, we design to investigate heterozygous SCN5A-knockout mice as a model for induced J wave syndrome and observe the effects of haploinsufficiency SCN5A gene mutation on ischemic induced J wave, by using coronary arterial infusion of wedge shaped tissue of the mice ventricle, the recording of floating glass microelectrode, synchronized ECG, and whole cell patch clamp on these cardiac cells as well as the medication intervention study. The results may clarify the possible mechanisms why the patients with haploinsufficiency SCN5A gene mutation are predisposed to TdP, providing theoretical and experimental basis for the clinical diagnosis and treatment of ischemic induced J wave syndrome in IHD patients.