Electrophysiological characteristics of complex fractionated electrograms and high frequency activity in atrial fibrillation

Background It is unclear whether atrial substrate with complex fractionated electrograms (CFAEs) is related to arrhythmogenesis. This study aimed to investigate the electrophysiology in CFAE and high dominant frequency (DF) areas. Methods and results Atrial fibrillation (AF) was induced by rapid atrial pacing in heart failure (HF) rabbits (4 weeks after coronary artery ligation). Real-time substrate mapping, multielectrode array, and monophasic action potential recordings were used to study areas of CFAE and DF. Conventional microelectrode and western blot were used to record the action potentials (APs) and protein expression in isolated tissue preparations. CFAE site with high DF had the most depolarized resting membrane potential, highest incidence of early and delayed afterdepolarizations, and steepest maxima slope of 90% of AP duration (APD₉₀) restitution curve (RC) compared to CFAE site with low DF or non-CFAE sites. CFAE site with high DF exhibited the slowest conduction velocity and shortest wavelength than the other areas. Upregulation of the Na⁺-Ca^{2 +} exchanger (NCX), apamin-sensitive small-conductance Ca^{2 +}-activated K⁺ channel type 2 (SK2) and sarcoplasmic reticulum Ca^{2 +}-ATPase, and downregulation of the Kir2.1 were found at CFAE site with high DF compared to that observed in the 3 other areas. Inhibition of the NCX and SK channels prolonged the APD ₉₀, flattened the maximum slope of RC, and suppressed AF. Conclusions CFAE site with high DF had an arrhythmogenic property differing significantly from the other areas of LA in an HF rabbit model, which may contribute to the genesis of AF.