Atrial fibrillation (AF) is a critical health problem that promotes stroke and heart failure, and is associated with increased risk of mortality. The global incidence of AF is increasing, as a result of shifts in diet, lifestyle and mean age of the population. Oxidant stress has numerous cellular origins and can result from mitochondrial dysfunction (uncoupling of the electron transport chain), upregulation of the activity of NADPH oxidase isoforms (NOXs), upregulation and/or uncoupling of nitric oxide synthases; and altered expression or distribution of myeloperoxidase. Oxidant stress and inflammatory mechanisms are often interrelated, as inflammatory cell activation frequently leads to oxidant generation to target perceived threats. Oxidant stress can promote autonomic changes, and is typically associated with sympathetic activation and vagal withdrawal.
As antiarrhythmic therapies focused on ion channel blockade have proved largely ineffective, upstream therapies that target pathways leading to the onset of AF have attracted increased attention. Although oxidant stress has been documented in human atrial specimens and in several experimental AF models, the therapeutic potential of non-specific antioxidants seems rather limited. Nominally pleiotropic agents including statins, ACE-inhibitors and aldosterone antagonists have been associated with an attenuation of systemic and atrial oxidant generation. The hypothesis that agents which more specifically target oxidant generation will contribute to a reduction in the burden of AF, reduce the incidence of stroke or limit the associated risk of heart failure and mortality is attractive but unproven. Efforts to identify and more selectively target the most significant sources of oxidant stress in AF may have great clinical benefit.
Atrial fibrillation (AF) is a critical health problem that promotes stroke and heart failure, and is associated with increased risk of mortality. The global incidence of AF is increasing, as a result of shifts in diet, lifestyle and mean age of the population. Oxidant stress has numerous cellular origins and can result from mitochondrial dysfunction (uncoupling of the electron transport chain), upregulation of the activity of NADPH oxidase isoforms (NOXs), upregulation and/or uncoupling of nitric oxide synthases; and altered expression or distribution of myeloperoxidase. Oxidant stress and inflammatory mechanisms are often interrelated, as inflammatory cell activation frequently leads to oxidant generation to target perceived threats. Oxidant stress can promote autonomic changes, and is typically associated with sympathetic activation and vagal withdrawal.
As antiarrhythmic therapies focused on ion channel blockade have proved largely ineffective, upstream therapies that target pathways leading to the onset of AF have attracted increased attention. Although oxidant stress has been documented in human atrial specimens and in several experimental AF models, the therapeutic potential of non-specific antioxidants seems rather limited. Nominally pleiotropic agents including statins, ACE-inhibitors and aldosterone antagonists have been associated with an attenuation of systemic and atrial oxidant generation. The hypothesis that agents which more specifically target oxidant generation will contribute to a reduction in the burden of AF, reduce the incidence of stroke or limit the associated risk of heart failure and mortality is attractive but unproven. Efforts to identify and more selectively target the most significant sources of oxidant stress in AF may have great clinical benefit.