Oxidative Stress on Pulmonary Vein and Left Atrium Arrhythmogenesis

Background: Oxidative stress and pulmonary veins (PVs) play critical roles in the pathophysiology of atrial fibrillation. The purpose of the present study was to investigate whether oxidative stress and antioxidant agents can change the electrophysiological characteristics of the left atrium (LA) and PVs. Methods and Results: Conventional microelectrodes were used to record the action potentials (APs) in isolated rabbit PV and LA specimens before and after H2O2 administration with or without ascorbic acid or N-mercaptopropionyl-glycine (N-MPG, a free radical OH scavenger). H2O2 (0.02 and 0.2 mmol/L) decreased the PV spontaneous rates from 2.0 0.1 Hz to 1.6 0.1 Hz, and 1.7 0.1 Hz (n=10, P<0.05), but H2O2 (2 mmol/L) increased PV spontaneous rates from 2.0 +/- 0.1 Hz to 2.8 +/- 0.2 Hz. H2O2 easily induced PV burst firing and early afterdepolarizations, but not in the LA. H2O2 shortened the AP duration and increased the contractile force to a greater extent in the LA than in PVs. In addition, the H2O2-induced PV burst firing and increasing spontaneous rates were suppressed or attenuated by pretreatment with ascorbic acid (1 mmol/L) or N-MPG (10 mmol/L). Conclusions: H2O2 significantly changed the electrophysiological characteristics of PV and LA through activation of free radicals and may facilitate the occurrence of atrial fibrillation. (Circ J 2010; 74: 1547-1556)