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J Am Coll Cardiol, 2001; 38:1757-1765
© 2001 by the American College of Cardiology Foundation
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EXPERIMENTAL STUDY

Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium

Tsu-Juey Wu, MD*,* {dagger}, Young-Hoon Kim, MD, FACC{dagger}, Masaaki Yashima, MD{dagger}, Charles A. Athill, MD{dagger}, Chih-Tai Ting, MD, PhD*, Hrayr S. Karagueuzian, PhD, FACC{dagger} and Peng-Sheng Chen, MD, FACC{dagger}

* 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
{dagger} Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and University of California at Los Angeles School of Medicine, Los Angeles, California, USA

Manuscript received December 27, 2000; revised manuscript received May 25, 2001, accepted August 10, 2001.

* Reprint requests and correspondence: Dr. Tsu-Juey Wu, Division of Cardiology, Department of Medicine, Taichung Veterans General Hospital, 160, Section 3, Chung-Kang Road, Taichung, Taiwan
tjwu{at}vghtc.vghtc.gov.tw

OBJECTIVES

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 µmol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD90 was measured during regular pacing (S1) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S2).

RESULTS

At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD90 from 124 ± 15 ms to 72 ± 9 ms (p < 0.01) with 1 to 2.5 µmol/l of ACh, S2 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 µmol/l, the APD90 was further shortened to 40 ± 12 ms (p < 0.01); S2 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 APD90 <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.

Abbreviations and Acronyms
  ACh = acetylcholine
  AF = atrial fibrillation
  APD = action potential duration
  CV = conduction velocity
  ECG = electrocardiogram
  RCA = right coronary artery
  TMP = transmembrane potential




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