Background: The Sodium Glucose Transporter 2 (SGLT2)-inhibitor, empagliflozin, reduces death from cardiovascular causes. We hypothesized that the mechanism involved direct protection against Ischemia- Reperfusion (IR) injury and improved post-ischemic mitochondrial function.
Methods: We examined infarct size (series I) and mitochondrial respiration (series II) in four groups of isolated perfused hearts from male Wistar rats: Sham-operated hearts (Sham group), IR-injured hearts (IR group), hearts treated with ischemic preconditioning (IPC) by 2 × 5 min. cycles of IR prior to sustained ischemia (IPC group), and hearts co-perfused with 2.14 mg/l of empagliflozin 10 min. prior to sustained ischemia (EMPA group).
Results: In contrast to IPC, empagliflozin did not reduce infarct size compared to the IR group, when given 10 min prior to the acute myocardial infarction. Empagliflozin improved post-ischemic complex I+II respiration compared to the IR group. This improvement was similar to IPC. In contrast to the improved complex I respiration by IPC, empagliflozin mainly improved complex II respiration. Empagliflozin hearts had significantly higher respiration in oligomycin induced state 4 than the sham and IR group, indicating that empagliflozin modulates the inner mitochondrial membrane.
Conclusion: In conclusion, empagliflozin yielded no acute cardioprotection in the isolated perfused non-diabetic rat heart. Empagliflozin mainly improved complex II respiration and increased permeability of the inner membrane, providing a potential explanation for the positive long-term effects observed in post infarction myocardial dysfunction.