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Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism
Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empa...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546214/ https://www.ncbi.nlm.nih.gov/pubmed/34712142 http://dx.doi.org/10.3389/fphar.2021.758080 |
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author | Tan, Yunke Yu, Kai Liang, Lian Liu, Yuanshan Song, Fengqing Ge, Qiulin Fang, Xiangshao Yu, Tao Huang, Zitong Jiang, Longyuan Wang, Peng |
author_facet | Tan, Yunke Yu, Kai Liang, Lian Liu, Yuanshan Song, Fengqing Ge, Qiulin Fang, Xiangshao Yu, Tao Huang, Zitong Jiang, Longyuan Wang, Peng |
author_sort | Tan, Yunke |
collection | PubMed |
description | Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA. |
format | Online Article Text |
id | pubmed-8546214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85462142021-10-27 Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism Tan, Yunke Yu, Kai Liang, Lian Liu, Yuanshan Song, Fengqing Ge, Qiulin Fang, Xiangshao Yu, Tao Huang, Zitong Jiang, Longyuan Wang, Peng Front Pharmacol Pharmacology Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8546214/ /pubmed/34712142 http://dx.doi.org/10.3389/fphar.2021.758080 Text en Copyright © 2021 Tan, Yu, Liang, Liu, Song, Ge, Fang, Yu, Huang, Jiang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Tan, Yunke Yu, Kai Liang, Lian Liu, Yuanshan Song, Fengqing Ge, Qiulin Fang, Xiangshao Yu, Tao Huang, Zitong Jiang, Longyuan Wang, Peng Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title | Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title_full | Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title_fullStr | Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title_full_unstemmed | Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title_short | Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism |
title_sort | sodium–glucose co-transporter 2 inhibition with empagliflozin improves cardiac function after cardiac arrest in rats by enhancing mitochondrial energy metabolism |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546214/ https://www.ncbi.nlm.nih.gov/pubmed/34712142 http://dx.doi.org/10.3389/fphar.2021.758080 |
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