Role of oxidative stress in ventricular arrhythmias

Oxidative stress facilitates ventricular arrhythmia by increasing the intracellular calcium current, the late sodium current, and gap junctional remodeling. Oxidative stress also promotes other pathologic processes, such as inflammation and myocardial fibrosis that are arrhythmogenic. Numerous studies link oxidative stress to arrhythmia and other cardiovascular disorders, and clinical trials have shown that treatment with antioxidants such as vitamin E produces only a modest benefit. The main sources of cardiac oxidative stress are mitochondria, nicotinamide adenine dinucleotide phosphate oxidase, and endothelial nitric oxide synthase uncoupling, all of which produce a variety of reactive oxygen species (ROS). ROS are highly reactive molecules that interact with proteins and lipids, and they exert their arrhythmic effect via those lipid and protein modifications. Antioxidant therapy may target the sources of ROS production or scavenging oxygen radicals or they may work by preventing the key activation and modifications occurring downstream from ROS production that result in arrhythmia. In this chapter, the above-mentioned concepts are discussed.