Mechanisms of sudden cardiac death: oxidants and metabolism

Circ Res. 2015 Jun 5;116(12):1937-55. doi: 10.1161/CIRCRESAHA.116.304691.

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.

Keywords: cardiac arrhythmias; death, sudden, cardiac; metabolism; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / metabolism
  • Calcium Signaling
  • Cardiovascular Agents / pharmacology
  • Cardiovascular Agents / therapeutic use
  • Death, Sudden, Cardiac / etiology*
  • Death, Sudden, Cardiac / prevention & control
  • Gap Junctions / physiology
  • Heart Conduction System / physiopathology
  • Heart Diseases / metabolism*
  • Homeostasis
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Membrane Potentials
  • Metabolic Diseases / complications
  • Metabolic Diseases / physiopathology
  • Mitochondria, Heart / metabolism
  • Myocardium / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Potassium / physiology
  • Reactive Oxygen Species
  • Sodium / physiology

Substances

  • Cardiovascular Agents
  • Ion Channels
  • Reactive Oxygen Species
  • Sodium
  • Potassium