Empagliflozin Reduces Arrhythmias In Mice By Improving Ventricular Remodeling And Electrical Remodeling After Myocardial Infarctio

Aims: To discuss the effects of empagliflozin(EMPA),an SGLT2 inhibitor,on cardiac structural remodeling and electrical remodeling in mice with myocardial infarction.And then further discuss how empagliflozin plays its antiarrhythmic role in mice after myocardial infarction by alleviating the level of structural remodeling and electrical remodeling.Thus achieving its unique cardiovascular protective effect..Methods: Male C57BL/6 mice aged 8 weeks were selected and the myocardial infarction model was established by ligation of LAD to induce myocardial ischemia.Mice were divided into 4 groups(WT,WT+EMPA,MI,MI+EMPA)by intragastric administration empagliflozin(10mg/Kg/day).The echocardiographic data were measured at 3,7 and 14 days after myocardial infarction.Electrocardiogram(ECG)was measured one week after MI to analyze the specific changes of ECG.In addition,real-time quantitative analysis was carried out on the tissues of the four groups of mice by PCR experimental technology,and the changes of each index in the four groups of mice were further analyzed.The effect of empagliflozin on the cardiac protection of mice after myocardial infarction was further investigated by optical mapping.Results: Treatment with Empagliflozin significantly reduced the structural remodeling in mice with myocardial infarction.By optical mapping,we observed that empagliflozin did not change APD80 and Ca T80 in normal mice after acute infusion of empagliflozin(10 μmol/L).However,APD80 and Ca T80 were significantly shortened in mice with MI at all PCL levels(200,150,120 and 100ms).In addition,empagliflozin can significantly increase cardiac conduction velocity in mice with myocardial infarction,but did not significantly alter cardiac conduction velocity in normal mice.On the other hand,acute infusion of empagliflozin improved the AP rise time and Ca T rise time in mice with myocardial infarction to some extent,but did not change in the hearts of normal mice.Using the S1/S2 pacing procedure,we observed that empagliflozin clearly reduced the incidence and susceptibility of ventricular fibrillation in mice with MI.Conclusions: Empagliflozin can play an antiarrhythmic role by improving the structural remodeling and electrical remodeling level of the heart after myocardial infarction in mice.The results showed that empagliflozin could significantly improve the cardiac function of mice with myocardial infarction after administration of empagliflozin,indicating that empagliflozin could clearly improve the structural remodeling of mice after myocardial infarction.On the other hand,empagliflozin exerts its protective ability to reduce the risk of arrhythmia at the acute level by inhibiting the prolongation of APD and reducing the interference of calcium ions.At the chronic level,empagliflozin may further enhance its protective effect by reducing the level of ion channels.