Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition

Norihiko Ono, Hideki Hayashi, Ayaka Kawase, Shien Fong Lin, Hongmei Li, James N. Weiss, Peng Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Aging and glycolytic inhibition (GI) are known to alter intracellular calcium ion (Cai2+) handling in cardiac myocytes, causing early afterpotentials (EADs) and delayed afterpotentials. We hypothesized that aging and GI interact synergistically in intact hearts to generate EADs and triggered activity leading to atrial fibrillation (AF). We studied isolated and Langendorff-perfused hearts of young (age 3-5 mo, N = 8) and old (age 27-29 mo, N = 14) rats subjected to GI (0 glucose + 10 mmol/l pyruvate). Epicardial atrial activation maps were constructed using optical action potentials, while simultaneously monitoring Cai2+ by means of dual-voltage and calcium-sensitive fluorescent dyes. During GI, spontaneous AF occurred in 13 of 14 old but in no young rats. AF was initiated by EAD-induced triggered activity at the left atrial pulmonary vein junction (LA-PVJ). The triggered activity initially propagated as single wave front, but within 1 s degenerated into multiple wavelets. The EADs and triggered activity in the old atria were associated with significantly elevated diastolic Cai2+ levels at the LA-PVJ, where the time constant τ of the Cai 2+ transient decline and action potential duration were significantly (P < 0.01) prolonged compared with atrial sites 5 mm away from LA-PVJ. During GI and rapid atrial pacing, spatially discordant APD and Ca i2+ transient alternans developed in the old but not young atria, leading to AF. Atria in old rats had significantly more fibrotic tissue than atria in young rats. We conclude that GI interacts with the aged and fibrotic atria to amplify Cai2+ handling abnormalities that facilitate EAD-mediated triggered activity and AF.

Original languageEnglish (US)
Pages (from-to)H639-H648
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • Action potential
  • Atrial fibrillation
  • Calcium transient
  • Early afterdepolarization
  • Interstitial fibrosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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