Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity.
BACKGROUND
Atrial fibrillation (AF) at times recurs immediately after termination of the arrhythmia. The mechanism(s) responsible for the extrasystole that reinduces AF is largely unknown. We hypothesized that abbreviation of action potential duration (APD) would permit very rapid rates of excitation, known to induce intracellular calcium loading, which in turn could promote delayed and/or early afterdepolarizations (EADs).


RESULTS
Acetylcholine (ACh, 1 micromol/L) was used to abbreviate atrial APD and permit rapid-pacing induction of AF in isolated coronary-perfused canine right atria. Transmembrane action potentials, pseudo-ECG, and tension development were recorded. AF or rapid pacing was associated with an increase in tonic tension. Termination of AF or rapid pacing (cycle length, 150 to 80 ms) resulted in a dramatic rise of phasic tension, prolongation of repolarization of the initial beats at the regular rate (cycle length, 700 ms), and the development of late phase 3 EADs and extrasystoles. These extrasystoles initiated AF in 15 cases (involving 9 right atria) within the first 11 seconds after termination of AF or rapid pacing. This novel EAD mechanism is observed only in association with marked APD abbreviation. The calcium channel blocker nifedipine reduced, and the sarcoplasmic reticulum calcium release blocker ryanodine eliminated, the post-rapid pacing-induced increase in phasic tension, late phase 3 EADs, and extrasystoles that initiate AF.


CONCLUSIONS
These data suggest that calcium overload conditions present after termination of vagally mediated AF contribute to the development of late phase 3 EAD-induced triggered activity and that this mechanism may be responsible for the extrasystolic activity that reinitiates AF.
Burashnikov
Alexander
A
Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501, USA. sasha@mmrl.edu
Antzelevitch
Charles
C
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology; D016275:Atrial Function; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D046508:Culture Techniques; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects; D007700:Kinetics; D008955:Models, Cardiovascular; D009543:Nifedipine / Q000494:pharmacology; D012008:Recurrence; D012433:Ryanodine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D012433:Ryanodine; D009543:Nifedipine; D000109:Acetylcholine