Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

Yang, Kai-Chien; Kyle, John W.; Makielski, Jonathan C.; Dudley, Samuel C.

doi:10.1161/circresaha.116.304691

Cited by 127Cardiac electrophysiology and arrhythmiasCardiac Ischemia and ReperfusionCardiac pacing and defibrillation studies

Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

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Yang, Kai-Chien, Kyle, John W., Makielski, Jonathan C., Dudley, Samuel C.·2015·Circulation Research

DOI 10.1161/circresaha.116.304691PMC PMC4458707

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Abstract

Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. Because conventional antiarrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD.

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Ventricular tachycardia evolving to ventricular fibrillation often precedes sudden cardiac death.
“In general, ventricular tachycardia, evolving to ventricular fibrillation, often precedes sudden cardiac death [2].”
From Modeling of artifacts in the wrist photoplethysmogram: Application to the detection of life-threatening arrhythmias (2021) · cites this paper as [2]

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Calcium Signaling and Reactive Oxygen Species in Mitochondria
Bertero, E., & Maack, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.310082 · Cited by 616 · see citing works
Sudden cardiac death: epidemiology, pathogenesis and management
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Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring
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Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia
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Murine Electrophysiological Models of Cardiac Arrhythmogenesis
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SESN2 protects against doxorubicin-induced cardiomyopathy via rescuing mitophagy and improving mitochondrial function
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Ventricular Arrhythmias in First Acute Myocardial Infarction: Epidemiology, Mechanisms, and Interventions in Large Animal Models
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Mitochondrial energetics and calcium coupling in the heart
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Sestrin 2 protects against LPS-induced acute lung injury by inducing mitophagy in alveolar macrophages
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Arrhythmias as Presentation of Genetic Cardiomyopathy
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Edaravone and cyclosporine A as neuroprotective agents for acute ischemic stroke
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SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond
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Epigenetic Control of Mitochondrial Function in the Vasculature
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Mitochondrial health, the epigenome and healthspan
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Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk
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Left ventricular hypertrophy and sudden cardiac death
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Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart
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Sudden Cardiac Death in Diabetes and Obesity: Mechanisms and Therapeutic Strategies
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IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias
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Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms
van Opbergen, C. J. M., den Braven, L., Delmar, M., & van Veen, T. A. B. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01496 · Cited by 44 · see citing works
Alliin alleviates LPS-induced pyroptosis via promoting mitophagy in THP-1 macrophages and mice
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Proposed pathophysiologic framework to explain some excess cardiovascular death associated with ambient air particle pollution: Insights for public health translation
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Sudden death in epilepsy: the overlap between cardiac and neurological factors
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Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats
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Baseline and long-term gamma-glutamyltransferase, heart failure and cardiac arrhythmias in middle-aged Finnish men: Prospective study and pooled analysis of published evidence
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Cardiac arrhythmogenesis: roles of ion channels and their functional modification
Lei, M., Salvage, S. C., Jackson, A. P., & Huang, C. L.-H. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1342761 · Cited by 36 · see citing works
Metabolic Flexibility and Dysfunction in Cardiovascular Cells
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Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice
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Regulation of energy metabolism by combination therapy attenuates cardiac metabolic remodeling in heart failure
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Differential effects of superoxide and hydrogen peroxide on myogenic signaling, membrane potential, and contractions of mouse renal afferent arterioles
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Cardiomyocyte electrophysiology and its modulation: current views and future prospects
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Pinocembrin mediates antiarrhythmic eﬀects in rats with isoproterenol-induced cardiac remodeling
Chen, X., Wan, W., Ran, Q., Ye, T., Sun, Y., Liu, Z., Liu, X., Shi, S., Qu, C., Zhang, C., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174799 · Cited by 31 · see citing works
Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress
Hang, C., Moawad, M. S., Lin, Z., Guo, H., Xiong, H., Zhang, M., Lu, R., Liu, J., Shi, D., Xie, D., et al. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02383-x · Cited by 33 · see citing works
Sodium–Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism
Tan, Y., Yu, K., Liang, L., Liu, Y., Song, F., Ge, Q., Fang, X., Yu, T., Huang, Z., Jiang, L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.758080 · Cited by 27 · see citing works
Modeling of artifacts in the wrist photoplethysmogram: Application to the detection of life-threatening arrhythmias
Paliakaitė, B., Petrėnas, A., Sološenko, A., & Marozas, V. (2021) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2021.102421 · Cited by 24 · see citing works
The complex crosstalk between inflammatory cytokines and ventricular arrhythmias
Kouvas, N., Kontogiannis, C., Georgiopoulos, G. A., Spartalis, Μ., Tsilimigras, D. I., Spartalis, E. D., Kapelouzou, A., Kosmopoulos, M., & Chatzidou, S. (2018) · Cytokine · doi:10.1016/j.cyto.2018.08.007 · Cited by 24 · see citing works
Obesity-associated alterations in cardiac connexin-43 and PKC signaling are attenuated by melatonin and omega-3 fatty acids in female rats
Beňová, T. E., Viczenczová, C., Bačová, B. S., Knezl, V., Dosenko, V., Rauchová, H., Zeman, M., Reiter, R. J., & Tribulová, N. (2018) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-018-3463-0 · Cited by 25 · see citing works
Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia
Salazar‐Ramírez, F., Ramos‐Mondragón, R., & García‐Rivas, G. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.623381 · Cited by 22 · see citing works
Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death
Carew, N. T., Schmidt, H. M., Yuan, S. S., Galley, J. C., Hall, R. M., Altmann, H. M., Hahn, S. A., Miller, M. P., Wood, K. C., Gabris, B. E., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci147120 · Cited by 23 · see citing works
Obesity and sudden cardiac death: Prevalence, pathogenesis, prevention and intervention
Yao, Y., Jia, X., & Li, B. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1044923 · Cited by 25 · see citing works
Iron deficiency as therapeutic target in heart failure: a translational approach
Bakogiannis, C., Briasoulis, Α., Mouselimis, D., Tsarouchas, A., Παπαγεωργίου, Ν., Papadopoulos, C. E., Fragakis, N., & Vassilikos, V. P. (2019) · Heart Failure Reviews · doi:10.1007/s10741-019-09815-z · Cited by 21 · see citing works
Mitochondrial Dysfunction Increases Arrhythmic Triggers and Substrates; Potential Anti-arrhythmic Pharmacological Targets
Saadeh, K., & Fazmin, I. T. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.646932 · Cited by 20 · see citing works
Cardiac Sodium Channel Mutations
Liu, M., Yang, K., & Dudley, S. C. (2016) · Current topics in membranes · doi:10.1016/bs.ctm.2015.12.004 · Cited by 20 · see citing works
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Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients
Zhang, Y., Güallar, E., Blasco‐Colmenares, E., Harms, A. C., Vreeken, R. J., Hankemeier, T., Tomaselli, G. F., & Cheng, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157035 · Cited by 19 · see citing works
Vidarabine, an anti-herpesvirus agent, prevents catecholamine-induced arrhythmias without adverse effect on heart function in mice
Suita, K., Fujita, T., Cai, W., Hidaka, Y., Jin, H., Prajapati, R., Umemura, M., Yokoyama, U., Sato, M., Knollmann, B. C., et al. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2121-4 · Cited by 18 · see citing works
Update on antiarrhythmic drug pharmacology
Huang, C. L.-H., Wu, L., Jeevaratnam, K., & Lei, M. (2020) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.14347 · Cited by 18 · see citing works
Introduction to a Compendium on Sudden Cardiac Death
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Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities
Sequeira, V., Waddingham, M. T., Tsuchimochi, H., Maack, C., & Pearson, J. T. (2023) · Journal of Molecular and Cellular Cardiology Plus · doi:10.1016/j.jmccpl.2023.100036 · Cited by 17 · see citing works
Cardiac Immunology: A New Era for Immune Cells in the Heart
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Anti‐malarial drugs: Mechanisms underlying their proarrhythmic effects
Saadeh, K., Kumar, N. N., Fazmin, I. T., Edling, C. E., & Jeevaratnam, K. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15959 · Cited by 16 · see citing works
Vulnerability for ventricular arrhythmias in patients with chronic coronary total occlusion
Assaf, A., Diletti, R., Hoogendijk, M. G., van der Graaf, M., Zijlstra, F., Szili‐Törok, T., & Yap, S. (2020) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2020.1793671 · Cited by 15 · see citing works
Atypical antipsychotics and oxidative cardiotoxicity: review of literature and future perspectives to prevent sudden cardiac death.
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A Spatiotemporal Ventricular Myocyte Model Incorporating Mitochondrial Calcium Cycling
Song, Z., Xie, L., Weiss, J. N., & Qu, Z. (2019) · Biophysical Journal · doi:10.1016/j.bpj.2019.09.005 · Cited by 15 · see citing works
Mitochondrial Oxidative Stress Mediates Bradyarrhythmia in Leigh Syndrome Mitochondrial Disease Mice
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Authors: Yang, K.-C., Kyle, J. W., Makielski, J. C., & Dudley, S. C.
Affiliations: University of Wisconsin–Madison (US)
ORCID: Yang, Kai-Chien
Dudley, Samuel C.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-06-05
Volume: 116
Issue: 12
Pages: 1937-1955
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.116.304691
PMC: PMC4458707
OpenAlex: W2141265094
Cited by: 127
References: 276
Citations by year: 2026: 6 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 19 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 7 · 2017: 9 · 2016: 13 · 2015: 3 · 2014: 1
FWCI: 7.76
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX000859)
National Heart, Lung, and Blood Institute (R01-HL-57414, R01HL122109, R01HL106592, R01HL104025, R01HL057414, R01HL071092, HL106592)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Keywords: sudden cardiac death, ventricular arrhythmias, myocardial metabolism, oxidative stress, redox imbalance, ion channel dysfunction, ion transporters, arrhythmogenic substrate, antiarrhythmic therapy, metabolic disorders
MeSH terms: Arrhythmias, Cardiac, Cardiovascular Agents, Heart Conduction System, Heart Diseases, Homeostasis, Humans, Ion Channels, Membrane Potentials, Metabolic Diseases, Mitochondria, Heart, Myocardium, Oxidation-Reduction, Potassium, Sodium, Ion Channel Gating, Death, Sudden, Cardiac, Reactive Oxygen Species, Gap Junctions, Oxidative Stress, Calcium Signaling

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Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

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