Aging-related increase to inducible atrial fibrillation in the rat model

Hideki Hayashi, Charles Wang, Yasushi Miyauchi, Chikaya Omichi, Hui Nam Pak, Shengmei Zhou, Toshihiko Ohara, William J. Mandel, Shien Fong Lin, Michael C. Fishbein, Peng Sheng Chen, Hrayr S. Karagueuzian

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127 Citations (Scopus)


Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. Methods and Results: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (> 30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 μM were studied in both groups. Heptanol 2 to 5 μM promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 μM, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 μM. In the old rats, AF could still be induced during perfusion of 2 μM heptanol. However, when its concentration was raised to 5 and 10 μM, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. Conclusion: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model.

Original languageEnglish
Pages (from-to)801-808
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Issue number8
Publication statusPublished - 2002 Aug

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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