Background: Oxidative Stress (OS) is thought to be an important mechanism underlying atrial fibrillation (AF). However, the precise role of OS in electrical remodeling in AF is not known. We hypothesize that reactive oxygen species (ROS) are dynamically involved in the creation of a vulnerable AF substrate.
Objective: To determine the effect of acute ROS scavenging on atrial electrophysiological characteristics during AF and sinus rhythm.
Methods: AF was induced in 10 dogs by rapid atrial pacing for 3-6 weeks. Epicardial high-density mapping was performed (130 electrodes, inter-elec. distance 2.5mm) before and 30 min after administration of N-acetylcysteine (NAC), a ROS scavenger. AF electrogram (EGM) characteristics were analyzed in 6 regions of the left and right atrium. The following AF characteristics were determined: Dominant Frequency (DF), Organization Index (OI), Fractionation Interval (FI), Shannon’s Entropy (ShEn). Effective refractory period (ERP) was also measured.
Results: NAC led to a modest but significant decrease in DF in nearly all atrial regions (example in figure A). OI and FI preferentially increased and ShEn decreased significantly in the PLA (figure B). NAC significantly prolonged ERP (68.7 ± 24.5, median 70.0 vs 92.5 ± 25.3, median 100.0, p = 0.027). Figure C shows an example of reduced fractionation and complexity of AF in response to NAC.
Conclusion: Acute scavenging of ROS significantly reduces the frequency and complexity of AF and appears to do so in a region-dependent manner. This slowing of AF appears to be at least partially driven by a prolongation of ERP. OS may be an important, dynamic mechanism underlying the formation and maintenance of the AF disease state.$$graphic_{8A0B7EBE-1A4F-4753-B1EC-971D0C7AC1B2}$$