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*

*Corresponding author for this work

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

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
Volume13
Issue number8
DOIs
StatePublished - 1 Jan 2002

Keywords

  • Aging
  • Atrial fibrillation
  • Cellular uncoupling
  • Fibrosis
  • Heptanol
  • Optical mapping
  • Reentry

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