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Seefeldt 2021 Sci Rep

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Seefeldt JM, Lassen TR, Vognstoft Hjortbak M, Jespersen NR, Kvist F, Hansen J, Boetker HE (2021) Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats. Sci Rep 11:9544.

» PMID: 33953281 Open Access

Seefeldt Jacob Marthinsen, Lassen Thomas Ravn, Vognstoft Hjortbak Marie, Jespersen Nichlas Riise, Kvist Frederikke, Hansen Jakob, Boetker Hans Erik (2021) Sci Rep

Abstract: The Sodium Glucose Co-Transporter-2 inhibitor, empagliflozin (EMPA), reduces mortality and hospitalisation for heart failure following myocardial infarction irrespective of diabetes status. While the findings suggest an inherent cardioprotective capacity, the mechanism remains unknown. We studied infarct size (IS) ex vivo in isolated hearts exposed to global IR injury and in vivo in rats subjected to regional myocardial ischemia reperfusion (IR) injury, in whom we followed left ventricular dysfunction for 28 days. We compared rats that were given EMPA orally for 7 days before, EMPA 1.5 h before IR injury and at onset of reperfusion and continued orally during the follow-up period. We used echocardiography, high resolution respirometry, microdialysis and plasma levels of β-hydroxybutyrate to assess myocardial performance, mitochondrial respiration and intermediary metabolism, respectively. Pretreatment with EMPA for 7 days reduced IS in vivo (65 ± 7% vs. 46 ± 8%, p < 0.0001 while administration 1.5 h before IR, at onset of reperfusion or ex vivo did not. EMPA alleviated LV dysfunction irrespective of the reduction in IS. EMPA improved mitochondrial respiration and modulated myocardial interstitial metabolism while the concentration of β-hydroxybutyric acid was only transiently increased without any association with IS reduction. EMPA reduces infarct size and yields cardioprotection in non-diabetic rats with ischemic LV dysfunction by an indirect, delayed intrinsic mechanism that also improves systolic function beyond infarct size reduction. The mechanism involves enhanced mitochondrial respiratory capacity and modulated myocardial metabolism but not hyperketonemia.

Bioblast editor: Plangger M O2k-Network Lab: DK Aarhus Boetker HE


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cardiovascular  Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2021-07