Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats

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 in...

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Autores principales: Seefeldt, Jacob Marthinsen, Lassen, Thomas Ravn, Hjortbak, Marie Vognstoft, Jespersen, Nichlas Riise, Kvist, Frederikke, Hansen, Jakob, Bøtker, Hans Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100147/
https://www.ncbi.nlm.nih.gov/pubmed/33953281
http://dx.doi.org/10.1038/s41598-021-89149-9
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author Seefeldt, Jacob Marthinsen
Lassen, Thomas Ravn
Hjortbak, Marie Vognstoft
Jespersen, Nichlas Riise
Kvist, Frederikke
Hansen, Jakob
Bøtker, Hans Erik
author_facet Seefeldt, Jacob Marthinsen
Lassen, Thomas Ravn
Hjortbak, Marie Vognstoft
Jespersen, Nichlas Riise
Kvist, Frederikke
Hansen, Jakob
Bøtker, Hans Erik
author_sort Seefeldt, Jacob Marthinsen
collection PubMed
description 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.
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spelling pubmed-81001472021-05-07 Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats Seefeldt, Jacob Marthinsen Lassen, Thomas Ravn Hjortbak, Marie Vognstoft Jespersen, Nichlas Riise Kvist, Frederikke Hansen, Jakob Bøtker, Hans Erik Sci Rep Article 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. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8100147/ /pubmed/33953281 http://dx.doi.org/10.1038/s41598-021-89149-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Seefeldt, Jacob Marthinsen
Lassen, Thomas Ravn
Hjortbak, Marie Vognstoft
Jespersen, Nichlas Riise
Kvist, Frederikke
Hansen, Jakob
Bøtker, Hans Erik
Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_full Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_fullStr Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_full_unstemmed Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_short Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_sort cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100147/
https://www.ncbi.nlm.nih.gov/pubmed/33953281
http://dx.doi.org/10.1038/s41598-021-89149-9
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