心肌缺血基础上的室性心律失常造成冠心病患者病死率增高。在缺血心肌，抑制峰钠电流的抗心律失常药物可减慢电活动的传导，发生致心律失常作用。我们前期研究证明晚钠电流抑制剂雷诺嗪可减少低灌注心脏中心室肌内外膜间的复极不均一性，减少跨壁复极离散度和心律失常的发生率，不影响室内传导的时间和模式，但延长复极时间。新型高选择性晚钠电流抑制剂在治疗心肌缺血相关心律失常方面可能有其独特性，需要明确其作用机制和与钙信号相关信号通路。本研究建立全心缺血的整体心脏模型，观察高选择性晚钠电流抑制剂eleclazine在缺血心脏对动作电位时程和QT间期、心室肌复极离散度、室内传导时间及模式、室性心律失常发生率及相关信号通路CaMKII磷酸化和Nav1.5表达水平的变化，证明晚钠电流与缺血相关室性心律失常之间的关系及选择性针对晚钠电流的干预措施在电生理和分子层面的优势，证明其在缺血心脏病患者的优势与应用前景。

Myocardial ischemia induced by coronary heart disease greatly increases the mortality due to the increased risk of ventricular arrhythmias. In the ischemic myocardium, antiarrhythmic drugs that inhibit peak sodium current can slow the intraventricular conduction of electrical activity and induce arrhythmias. In our previous studies, we found that the late sodium current inhibitor ranolazine reduced the dispersion of repolarization between the epicardium and endocardium of ventricular (transmural dispersion of repolarization, TDR), diminished ventricular arrhythmia and did not affect the intra ventricular conduction time and pattern. However, ranolazine prolonged repolarizaion duration. It is suggested that the late sodium current blocker was unique in the treatment of ischemia-related ventricular arrhythmias with incomplete understanding in the mechanisms related to sodium-calcium signal pathway. In this study, we will further determine the relationship between late sodium current and ischemia-related ventricular arrhythmias by studying QT interval, TDR, incidence of ventricular arrhythmias, single cell action potential and expression level of CaMKII and phosphorylated Nav1.5 in low-flow induced global ischemic heart model using high selective late sodium current inhibitor eleclazine (GS-6615). The results will further clarify the relationship between late sodium current and ischemia-related ventricular arrhythmias, and the possible therapeutic value and safety of late sodium current inhibitor in both electrophysiology and molecular levels. This study will help us to prove the advantages of late sodium inhibitor and application prospects in patients with ischemic heart disease.