ArticleCardiovascular diabetology2021
Empagliflozin protects the heart against ischemia/reperfusion-induced sudden cardiac death.
Article in Cardiovascular diabetology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Empagliflozin modulates microRNA expression in human primary cardiomyocytes under CoClInternational journal of cardiology. Cardiovascular risk and prevention · 2026Article
- Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.Cardiovascular drugs and therapy · 2025Article
- S100A4-shRNA mitigates autophagy, reduces inflammation, and improves cardiac functionality in MIRI.International journal of cardiology. Cardiovascular risk and prevention · 2025Article
- Aloperine Alleviates Myocardial Injury Induced by Myocardial Ischemia and Reperfusion by Activating the ERK1/2/β-catenin Signaling Pathway.Cardiovascular drugs and therapy · 2025Article
- The Influence of Empagliflozin on the Expression of Mitochondrial Regulatory Proteins in Human Myocardium in an Ex Vivo Model of Short-Term Atrial Tachypacing.International journal of molecular sciences · 2025Article
- Protective Mechanisms of SGLTi in Ischemic Heart Disease.Journal of cardiovascular translational research · 2024Review
- The Off-Target Cardioprotective Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors: An Overview.International journal of molecular sciences · 2024Review
- Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.Cardiovascular diabetology · 2024Article
- Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction.International journal of molecular medicine · 2024Article
- Dapagliflozin prevents ERK activation and SGLT2-dependent endoglin upregulation in a mechanically provoked cardiac injury model.Physiological reports · 2024Article
- Canagliflozin Pretreatment Attenuates Myocardial Dysfunction and Improves Postcardiac Arrest Outcomes After Cardiac Arrest and Cardiopulmonary Resuscitation in Mice.Cardiovascular drugs and therapy · 2024Article
- Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Review
- Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil (5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB signaling pathway in rats.Toxicological research · 2024Article
- Article
- Divergent electrophysiologic action of dapagliflozin and empagliflozin on ventricular and atrial tachyarrhythmias in isolated rabbit hearts.Frontiers in cardiovascular medicine · 2024Article
- Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection.ImmunoHorizons · 2023Article
- Diabetes Mellitus in Acute Coronary Syndrome.Life (Basel, Switzerland) · 2023Review
- Article
- Molecular therapy of cardiac ischemia-reperfusion injury based on mitochondria and ferroptosis.Journal of molecular medicine (Berlin, Germany) · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEmpagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor used to lower blood sugar in adults with type 2 diabetes. Empagliflozin also exerts cardioprotective effects independent from glucose control, but its benefits on arrhythmogenesis and sudden cardiac death are not known. The purpose of this study was to examine the effect of empagliflozin on myocardial ischemia/reperfusion-provoked cardiac arrhythmia and sudden cardiac death in vivo.
methodsMale Sprague Dawley rats were randomly assigned to sham-operated, control or empagliflozin groups. All except for the sham-operated rats were subjected to 5-min left main coronary artery ligation followed by 20-min reperfusion. A standard limb lead II electrocardiogram was continuously measured throughout the experiment. Coronary artery reperfusion-induced ventricular arrhythmogenesis and empagliflozin therapy were evaluated. The hearts were used for protein phosphorylation analysis and immunohistological assessment.
resultsEmpagliflozin did not alter baseline cardiac normal conduction activity. However, empagliflozin eliminated myocardial vulnerability to sudden cardiac death (from 69.2% mortality rate in the control group to 0% in the empagliflozin group) and reduced the susceptibility to reperfusion-induced arrhythmias post I/R injury. Empagliflozin increased phosphorylation of cardiac ERK1/2 after reperfusion injury. Furthermore, inhibition of ERK1/2 using U0126 abolished the anti-arrhythmic action of empagliflozin and ERK1/2 phosphorylation.
conclusionsPretreatment with empagliflozin protects the heart from subsequent severe lethal ventricular arrhythmia induced by myocardial ischemia and reperfusion injury. These protective benefits may occur as a consequence of activation of the ERK1/2-dependent cell-survival signaling pathway in a glucose-independent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.