Role of Oxidative Stress in Mediating Elevated Atrial Fibrillation by Tumor Necrosis Factor-Alpha.

摘要

Atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice, is a major source of morbidity and mortality, and is highly associated with inflammation and oxidative stress. In the present study, we show that acute exposure of mice atrial tissue to tumor necrosis factor-alpha (TNF-alpha) increases susceptibility to AF. We further show that acute exposure to TNF-alpha led to increased spontaneous sarcoplasmic reticulum (SR) calcium release and generated triggered activities in isolated mice atrial myocytes. This increase in spontaneous SR calcium activity was found to be due to elevated reactive oxygen species production from mitochondria and NADPH oxidase sources triggered by TNF-alpha. Hence we concluded that acute exposure to TNF-alpha leads to elevated oxidative stress that increases spontaneous SR Ca 2+ release and triggered activity through which it can lead to AF induction and maintenance.