Mitochondrial Dysfunction in Atrial Fibrillation: The Need for a Strong Pharmacological Approach

Abstract

Despite great progress in treating atrial fibrillation (AF), especially with the development of increasingly effective invasive techniques for AF ablation, many unanswered questions remain regarding the pathogenic mechanism of the arrhythmia and its prevention methods. The development of AF is based on anatomical and functional alterations in the cardiomyocyte resulting from altered ionic fluxes and cardiomyocyte electrophysiology. Electric instability and electrical remodeling underlying the arrhythmia may result from oxidative stress, also caused by possible mitochondrial dysfunction. The role of mitochondrial dysfunction in the pathogenesis of AF is not yet fully elucidated; however, the reduction in AF burden after therapeutic interventions that improve mitochondrial fitness tends to support this concept. This selected review aims to summarize the mechanisms of mitochondrial dysfunction related to AF and the current pharmacological treatment options that target mitochondria to prevent or improve the outcome of AF.

Keywords: arrhythmia; atrial fibrillation; mitochondrial dysfunction; oxidative stress.

Figure 1

Mitochondrial alterations in endothelial dysfunction. LDL-C, lipoprotein low density-concentration; Mt, mitochondrial; ROS, reactive oxygen species.

Figure 2

Electrogenesis of AF in mitochondrial dysfunction. ADP: adenosine diphosphate; ATP: adenosine triphosphate; ROS: radical oxidative species; SERCA: Sarco-Endoplasmic Reticulum Calcium ATPase; ↑: increase; ↓: reduction.