Effective antioxidant therapy for the management of arrhythmia

Abstract

“Reactive oxygen species-mediated reduction in the total sodium current reduces conduction velocity and facilitates re-entry, and other ionic effects of reactive oxygen species cause an increase in the inward current and intracellular calcium level, facilitating early afterdepolarization and delayed afterdepolarization.” Heart failure is the most important clinical condition that is associated with the increased risk of sudden cardiac death (SCD) [1] and with an increased level of reactive oxygen species (ROS) in the heart [2,3]. Numerous clinical risk factors for atrial fibrillation including hyperten sion, pulmonary diseases, surgery and aging, are all associated with oxidative stress [4]. The increased level of ROS associated with all major clinical risk factors for arrhythmia is indirect evidence that oxidative stress may be important in the genesis of both atrial and ventricular arrhythmias. Nevertheless, despite considerable evidence supporting the important role of oxidative stress in arrhythmia, clinical trials have failed to demonstrate the cardiovascular benefit of often-prescribed general antioxidants [5,6]. A greater understanding of the biology of ROS production and mechanisms, by which ROS facilitate arrhythmia, is essential to designing an effective antioxidant therapy for the treatment of arrhythmias. Cardiac sources of ROS Reactive oxygen species such as superoxide (O 2 •- ), hydrogen peroxide (H 2 O 2 ), hydroxyl radical ( • OH) and peroxynitrite (ONOO – )