Copyright © 2005, European Society of Cardiology
Region-specific, pacing-induced changes in repolarization in rabbit atrium: An example of sensitivity to the rare
Center for Molecular Therapeutics, Department of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, United States
* Corresponding author. College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 West 168 Street, PH 7West-321, New York, NY 10032, United States. Tel.: +1 212 305 8754. fax: +1 212 305 8351. Email address: mrr1{at}columbia.edu
Objective: In subsets of patients paroxysmal firing of ectopic foci in pulmonary veins or coronary sinus is an important cause of atrial fibrillation. This appears to represent a rare event overriding a dominant sinus mechanism to alter the rhythmic firing of the atrium. Hence, we tested the hypothesis that a rare stimulation pattern might alter the myocardial substrate, making it more susceptible to the initiation of arrhythmias.
Methods: In isolated right and left rabbit atria, a "rare" burst pacing protocol (BPP) was applied as follows: over 3 h, preparations were driven for 4.5 min from sinus node (SN) or Bachmann's bundle (BB) regions at cycle length (CL)=400 ms followed by 30 s of stimulation from coronary sinus (CS) or pulmonary vein (PV) at CL=200 ms. Microelectrodes were used to record action potentials at the end of 4.5 min of pacing at CL=400 ms. We then intervened with 5-min bigeminal pacing to probe atrial vulnerability to arrhythmias: S1 was delivered from SN or BB and S2 from CS or PV, respectively. S1–S2 interval was the shortest eliciting a propagated response.
Results: BPP shortened repolarization in CS and PV regions but not in SN or BB, resulting in increased dispersion of repolarization in right and decreased in left atria. Propranolol, atropine and losartan failed to alter the decrease in repolarization induced by BPP whereas apamin, nifedipine and ryanodine prevented BPP effects. Before BPP, bigeminy did not induce arrhythmias in either atrium, but after BPP, bigeminy significantly increased the incidence of arrhythmias in the right atrium.
Conclusions: BPP from foci outside the regions of dominant activation alters dispersion of atrial repolarization. Modulation of apamin-sensitive channels may contribute to the shortening of repolarization in CS and PV regions. Alterations of atrial repolarization gradient create an arrhythmogenic substrate and may be an early step in atrial electrophysiologic remodeling.
KEYWORDS Arrhythmia (mechanism); Atrial function; Membrane potential; Repolarization
Time for primary review 15 days
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