The most common cause of morbidity and death worldwide is acute myocardial infarction (AMI), which is typified by severe and deadly arrhythmias resulting from cardiac ischemia and reperfusion (CIR). We chose to investigate the possible cardioprotective activity of epiisopiloturine (EPI), an imidazole alkaloid presents in the leaves of Pilocarpus microphyllus, in an animal model of CIR in rats. Control rats were treated with 0.9% saline solution and then subjected to CIR (SS + CIR); they were compared to rats pretreated with either 10 mg/kg (EPI10 + CIR group) or 15 mg/kg EPI (EPI15 + CIR) before CIR. ECG analysis was used to assess the incidence of ventricular arrhythmias (VAs), atrioventricular block (AVB), and lethality (LET) brought on by CIR in these rats. Serum creatine kinase-MB (CK-MB) was assessed using a colorimetric assay. In comparison to the SS + CIR group, animals treated with EPI15 + CIR had lower AVB incidence, which decreased from 85.7% to 21.4%, while LET incidence decreased from 71.4% to 21.4%. In both EPI10 + CIR and EPI15 + CIR groups, serum CK-MB was lower than in SS + CIR positive controls. These findings suggest that administration of EPI (15 mg/kg) before CIR could reduce the incidences of AVB and LET, as well as cardiac injury markers, which suggests that, likely due to its antioxidant effects, EPI may be a promising drug to reduce LET in patients with severe and fatal arrhythmia due to AMI.