Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats

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 s...

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Autores principales:	Jacob Marthinsen Seefeldt, Thomas Ravn Lassen, Marie Vognstoft Hjortbak, Nichlas Riise Jespersen, Frederikke Kvist, Jakob Hansen, Hans Erik Bøtker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/164bc43e8fce4007a2d57ed07fec3e33
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spelling	oai:doaj.org-article:164bc43e8fce4007a2d57ed07fec3e332021-12-02T14:49:26ZCardioprotective effects of empagliflozin after ischemia and reperfusion in rats10.1038/s41598-021-89149-92045-2322https://doaj.org/article/164bc43e8fce4007a2d57ed07fec3e332021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89149-9https://doaj.org/toc/2045-2322Abstract 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.Jacob Marthinsen SeefeldtThomas Ravn LassenMarie Vognstoft HjortbakNichlas Riise JespersenFrederikke KvistJakob HansenHans Erik BøtkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacob Marthinsen Seefeldt Thomas Ravn Lassen Marie Vognstoft Hjortbak Nichlas Riise Jespersen Frederikke Kvist Jakob Hansen Hans Erik Bøtker Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
description	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.
format	article
author	Jacob Marthinsen Seefeldt Thomas Ravn Lassen Marie Vognstoft Hjortbak Nichlas Riise Jespersen Frederikke Kvist Jakob Hansen Hans Erik Bøtker
author_facet	Jacob Marthinsen Seefeldt Thomas Ravn Lassen Marie Vognstoft Hjortbak Nichlas Riise Jespersen Frederikke Kvist Jakob Hansen Hans Erik Bøtker
author_sort	Jacob Marthinsen Seefeldt
title	Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
title_short	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_sort	cardioprotective effects of empagliflozin after ischemia and reperfusion in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/164bc43e8fce4007a2d57ed07fec3e33
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Cardioprotective effects of empagliflozin after ischemia and reperfusion in rats

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