title: Region-specific, pacing-induced changes in repolarization in rabbit atrium: an example of sensitivity to the rare.
abstract: 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.
authors.affiliation: Center for Molecular Therapeutics, Department of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: David
authors.initials: D
authors.lastname: Hefer
authors.forename: Tove S
authors.initials: TS
authors.lastname: Rosen
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Michiel J
authors.initials: MJ
authors.lastname: Janse
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011667:Pulmonary Veins; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D044140:Receptor, Angiotensin, Type 1; D011976:Receptors, Muscarinic; D012433:Ryanodine; D001030:Apamin; D001285:Atropine; D011433:Propranolol; D009543:Nifedipine; D019808:Losartan