title: Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium.
abstract: OBJECTIVE
  We sought to evaluate the effects of progressive shortening of the action potential duration (APD) on atrial wave front stability.
  
  
  BACKGROUND
  The mechanisms of conversion from atrial flutter to atrial fibrillation (AF) are unclear.
  
  
  METHODS
  Isolated canine right atria were perfused with 1 to 5 micromol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD(90) was measured during regular pacing (S(1)) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S(2)).
  
  
  RESULTS
  At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD(90) from 124 +/- 15 ms to 72 +/- 9 ms (p < 0.01) with 1 to 2.5 micromol/l of ACh, S(2) pacing induced single, stable and stationary re-entrant wave fronts (307 +/- 277 cycles). They either anchored to pectinate muscles (5 tissues) or used pectinate muscles as part of the re-entry (4 tissues). When ACh was raised to 2.5 to 5 micromol/l, the APD(90) was further shortened to 40 +/- 12 ms (p < 0.01); S(2) pacing induced in vitro AF by two different mechanisms. In most episodes (n = 13), AF was characterized by rapid, nonstationary re-entry and multiple wave breaks. In three episodes with APD(90) <30 ms, AF was characterized by rapid, multiple, asynchronous, but stationary wave fronts.
  
  
  CONCLUSIONS
  Progressive APD shortening modulates atrial wave front stability and converts atrial flutter to AF by two mechanisms: 1) detachment of stationary re-entry from the pectinate muscle and the generation of multiple wave breaks; and 2) formation of multiple, isolated, stationary wave fronts with different activation cycle lengths.
authors.affiliation: Division of Cardiology, Department of Medicine, Taichung Veterans General Hospital and Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan. tjwu@vghtc.vghtc.gov.tw
authors.forename: T J
authors.initials: TJ
authors.lastname: Wu
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Yashima
authors.forename: C A
authors.initials: CA
authors.lastname: Athill
authors.forename: C T
authors.initials: CT
authors.lastname: Ting
authors.forename: H S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: P S
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001282:Atrial Flutter / Q000503:physiopathology*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D000109:Acetylcholine