Nicolaj Støttrup

Sodium Glucose Transporter 2 (SGLT2) Inhibition does not Protect the Myocardium from Acute Ischemic Reperfusion Injury but Modulates Post- Ischemic Mitochondrial Function

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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.
TidsskriftCardiovascular Pharmacology: Open Access
StatusUdgivet - 2017

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