Abstract 2891: Mechanisms of Atrial Tachyarrhythmias Associated With Chronic Atrial Ischemia
Background: Coronary artery disease (CAD) predisposes to atrial fibrillation (AF). We previously reported that acute atrial ischemia favors AF maintenance. However, the effects of chronic atrial ischemia/infarction on the atrial arrhythmic substrate are unknown.
Methods: Regional right atrial (RA) infarction was created in 18 dogs by ligating the right intermediate atrial artery (RIAA), which specifically supplies the RA free wall and not the ventricles (MI group). In 14 sham dogs, the RIAA was dissected and thread left without ligation. Holter ECGs were obtained on day 2 and 7 post-op. Open-chest EPS with 240 electrode mapping was performed at day 8, after which atrial cells were isolated from the infarct border zone (BZ) region. Action potentials (APs) were recorded with perforated patch methods and [Ca2+]i measured with Indo 1-AM.
Results: MI increased spontaneous ambulatory atrial ectopy: e.g., on day 7, isolated PACs: 662±281 beats/day in MI vs. 34±25 beats/day in sham dogs, p<0.05; atrial tachycardia: 52±21 episodes/day comprising 928±652 beats/day in MI dogs vs. 1±1 episodes/4±4 beats/day in sham dogs, p<0.01 for each. Atrial infarction reduced infarct zone (IZ) conduction velocity (69.7±3.7 vs. 88.6±2.6 cm/s, p<0.01), increased conduction heterogeneity (index, 2.4±0.2 vs. 1.4±0.1, p<0.0001), and prolonged induced AF duration (1146±259 vs. 30±14 s, p<0.01) by promoting IZ conduction block. BZ atrial cells showed delayed after depolarizations and increased triggered activity (9.7±1.1 vs. 5.5±0.8 events/min, p<0.01). Resting potential, AP amplitude, and APD were unchanged in MI dogs. BZ cells showed lower Ca2+-transient amplitudes (137±11 vs. 209±22 nM, 1 Hz, p<0.01) and diastolic Ca2+levels (62±6 vs. 81±7 nM, p<0.05). Caffeine-induced Ca2+transients were decreased by ~21% in BZ cells and had a faster decay (τ1302±74 ms, vs 1588±84 ms in sham, p<0.01), indicating accelerated Na+, Ca2+exchange.
Conclusions: Chronic atrial ischemia/infarction promotes AF maintenance by creating focal conduction abnormalities that anchor reentry, and causes abnormal Ca2+handling along with DAD-related triggered activity that induces atrial ectopic activity. These results provide novel insights into mechanisms of AF in patients with chronic CAD.