AUTHOR=Xue Genlong , Yang Xiaolei , Zhan Ge , Wang Xin , Gao Jinghan , Zhao Yong , Wang Xinying , Li Jiatian , Pan Zhenwei , Xia Yunlong 

TITLE=Sodium–Glucose cotransporter 2 inhibitor empagliflozin decreases ventricular arrhythmia susceptibility by alleviating electrophysiological remodeling post-myocardial-infarction in mice

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.988408

DOI=10.3389/fphar.2022.988408

ISSN=1663-9812

ABSTRACT=BACKGROUND Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in myocardial infarction (MI) patients, but the underlying mechanisms remain unknown. As arrhythmia is often occurred during myocardial infarction and is the main cause of death. 
OBJECTIVE The purpose of this study was to investigated the infulence of empagliflozin (Empa), an SGLT2 inhibitor, on cardiac electrophysiological remodeling and arrhythmia susceptibility of MI mice.
METHODS ECG was obtained from mice 1 week after MI to determine the QT interval. Electrophysiological study, optical mapping were performed to evaluate the function of Empa and underlying mechanism on post-myocardial infarction in mice.
RESULTS Empa treatment significantly reduced QT interval of MI mice. The membrane potential and intracellular Ca [Cai] were mapped from 13 MI hearts and 5 normal hearts by optical mapping technique. A dynamic pacing protocol was used to determine APD and [Cai] at baseline and after Empa (10 umol/L) infusion. Empa perfusion did not change APD80 and CaT80 in normal ventricles, while shortened them in infarct zone (IZ), bordering zone (BZ), remote zone (RZ) of MI hearts at 200 ms, 150 ms,120 ms,100 ms pacing cycle length. The conduction velocity of infarcted ventricles was 0.278 m/s and 0.533 m/s in normal ventricles at baseline. After Empa administration, the conduction velocity of infarcted ventricles increased to 0.363 m/s, whereas no significant changes were observed in normal ventricles. The AP rise time, CaT rise time and CaT tau time were improve after Empa perfusion in infarcted ventricles, whereas no significant changes were observed in normal ventricles. Empa decrease early afterdepolarizations (EADs), premature ventricular beats (PVBs) and ventricular fibrillation (VF) in infarcted ventricles. The number of phase singularities (baseline versus Empa, 6.26 versus 3.25), dominant frequency (20.52 versus 10.675 Hz), and ventricular fibrillation duration (1.072 versus 0.361s) during ventricular fibrillation in infarcted ventricles were all significantly decreased by Empa.
CONCLUSIONS Treatment with Empa improved post-MI electrophysiological remodeling and decreased substrate for VF of MI mice. The inhibitors of SGLT2 may be a new class of agents for the prevention of ventricles arrhythmia after chronic MI.