Left-to-right gradient of atrial frequencies during acute atrial fibrillation in the isolated sheep heart

Background - Recent studies demonstrated spatiotemporal organization in atrial fibrillation (AF). We hypothesized that waves emanating from sources in the left atrium (LA) undergo fragmentation, resulting in left-to-right frequency gradient. Our objective was to characterize impulse propagation across Bachmann's bundle (BB) and the inferoposterior pathway (IPP) during AF. Methods and Results - In 13 Langendorff-perfused sheep hearts, AF was induced in the presence of acetylcholine (ACh). Fast Fourier transform of optical and bipolar electrode recordings was performed. Frequency-dependent changes in the left-to-right dominant frequency (DF) gradient were studied by perfusing D600 (2 μmol/L) and by increasing ACh concentration from 0.2 to 0.5 μmol/L. BB and IPP were subsequently ablated. At baseline, a left-to-right decrease in DFs occurred along BB and IPP, resulting in an LA-right atrium (RA) frequency gradient of 5.7±1.4 Hz. Left-to-right impulse propagation was present in 81±5% and 80±10% of cases along BB and IPP, respectively. D600 decreased the highest LA frequency from 19.7±4.4 to 16.2±3.9 Hz (P<0.01) and raised RA DF from 8.6±2.0 to 10.7±1.8 Hz (P<0.05). An increase in ACh concentration increased the LA-RA frequency gradient from 4.9±1.8 to 8.9±1.8 Hz (P<0.05). Ablation of BB and IPP decreased RA DF from 10.9±1.2 to 9.0±1.5 Hz (P<0.01) without affecting LA DF (16.8±1.5 versus 16.9±1.8 Hz, P=NS). Conclusions - Left-to-right impulse propagation and frequency-dependent changes in the LA-RA frequency gradient during AF strongly support the hypothesis that this arrhythmia is the result of high-frequency periodic sources in the LA, with fibrillatory conduction away from such sources.