In the current study, using a 5-min period of ischemia followed by 20-min of reperfusion protocol, we were able to demonstrate that pretreatment with empagliflozin prior to myocardial ischemia reduced the incidence and severity of reperfusion-induced arrhythmogenesis and increased ERK1/2 phosphorylation (activation) post-I/R. This evidence concerns the gene MAPK3 and ischemia.