title: Mechanisms of sudden cardiac death: oxidants and metabolism.
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.
authors.affiliation: From the Department of Pharmacology (K.-C.Y.) and Division of Cardiology, Department of Internal Medicine (K.-C.Y.), National Taiwan University Hospital, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison (J.W.K., J.C.M.); and Lifespan Cardiovascular Institute, the Providence VA Medical Center, and Brown University, RI (S.C.D.).
authors.forename: Kai-Chien
authors.initials: KC
authors.lastname: Yang
authors.affiliation: From the Department of Pharmacology (K.-C.Y.) and Division of Cardiology, Department of Internal Medicine (K.-C.Y.), National Taiwan University Hospital, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison (J.W.K., J.C.M.); and Lifespan Cardiovascular Institute, the Providence VA Medical Center, and Brown University, RI (S.C.D.).
authors.forename: John W
authors.initials: JW
authors.lastname: Kyle
authors.affiliation: From the Department of Pharmacology (K.-C.Y.) and Division of Cardiology, Department of Internal Medicine (K.-C.Y.), National Taiwan University Hospital, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison (J.W.K., J.C.M.); and Lifespan Cardiovascular Institute, the Providence VA Medical Center, and Brown University, RI (S.C.D.). samuel_dudley@brown.edu jcm@medicine.wisc.edu.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Makielski
authors.affiliation: From the Department of Pharmacology (K.-C.Y.) and Division of Cardiology, Department of Internal Medicine (K.-C.Y.), National Taiwan University Hospital, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison (J.W.K., J.C.M.); and Lifespan Cardiovascular Institute, the Providence VA Medical Center, and Brown University, RI (S.C.D.). samuel_dudley@brown.edu jcm@medicine.wisc.edu.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
mesh_terms: D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D020013:Calcium Signaling; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D017629:Gap Junctions / Q000502:physiology; D006329:Heart Conduction System / Q000503:physiopathology; D006331:Heart Diseases / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials; D008659:Metabolic Diseases / Q000150:complications / Q000503:physiopathology; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011188:Potassium / Q000502:physiology; D017382:Reactive Oxygen Species; D012964:Sodium / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D007473:Ion Channels; D017382:Reactive Oxygen Species; D012964:Sodium; D011188:Potassium
keywords: cardiac arrhythmias; death, sudden, cardiac; metabolism; oxidative stress