Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

Abstract

Atrial fibrillation (AF) is the most common arrhythmia that requires medical attention, and its incidence is increasing. Current ion channel blockade therapies and catheter ablation have significant limitations in treatment of AF, mainly because they do not address the underlying pathophysiology of the disease. Oxidative stress has been implicated as a major underlying pathology that promotes AF; however, conventional antioxidants have not shown impressive therapeutic effects. A more careful design of antioxidant therapies and better selection of patients likely are required to treat effectively AF with antioxidant agents. Current evidence suggest inhibition of prominent cardiac sources of reactive oxygen species (ROS) such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and targeting subcellular compartments with the highest levels of ROS may prove to be effective therapies for AF. Increased serum markers of oxidative stress may be an important guide in selecting the AF patients who will most likely respond to antioxidant therapy.

Antioxidant Therapies in the Prevention and Treatment of Atrial Fibrillation

“…In the past few years experimental data and clinical evidence have tested the concept of antioxidant interventions to prevent AF. Besides statins, ACEIs and/or ARBs, several other interventions with antioxidant properties, such as Vitamin C and E, thiazolidinediones, N-acetylcysteine, probucol, nitric oxide donors or precursors, NADPH oxidase inhibitors, Xanthine oxidase inhibitors have emerged as novel strategies in the prevention and treatment of AF [6][7][8][9][10]. In this chapter, we aim to summarize recent evidence regarding antioxidant therapies in the prevention and treatment of atrial fibrillation…”

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

“…The major sources of ROS in the atria are: NADPH oxidases (NOX 1, 2 and 4), the electron transport chain (ETC), uncoupled NO synthase (NOS), and in some extent myeloperoxidase (MPO) [31,32]. Interestingly, the participation of ROS sources varies with the progression of the disease, an observation with important therapeutic implications.…”

“…ROS elevation aggravates AF evolution by affecting ionic currents, gap junctions, inflammation and fibrosis (see [32] for a recent review); therefore, targeting oxidative stress is nowadays regarded as a potential "upstream therapy" [34], especially when considering the fact that many of the current pharmacologic therapies lack atrial specificity or/and are proarrhythmic. Indeed, as recently suggested, primary prevention of AF and postoperative AF may benefit from NADPH oxidases inhibitors, whereas in persistent AF mitochondria-targeted antioxidants may prove to be most effective [32].…”

Selenium and oxidative stress modulation during extracorporeal circulation

“…134,140 Current data suggests that the development of POAF is multi-factorial involving both electrical and structural remodelling. Within this context, inflammation and oxidative stress are two key triggers [132][133][134][135] identified as being important components in its development; (although this study will not be examining the role of inflammation).…”

“…131,132 It is thought to be closely associated with the oxidative stress response and inflammation, [132][133][134][135] and while it can be self-limiting, there are numerous post-operative complications associated with AF including; hypotension and shock; thromboembolic events; renal failure; prolonged ICU stay 136 and higher long-term health care costs. 137,138 The standard course of treatment for AF in general includes rate and rhythm control and/or anti-coagulation.…”