Spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic nerve sprouting

Ayaka Numata, Yasushi Miyauchi, Norihiko Ono, Michael C. Fishbein, William J. Mandel, Shien Fong Lin, James N. Weiss, Peng Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticle

12 Scopus citations


Sympathetic Activation and Atrial Fibrillation. Background: Chronic left ventricular myocardial infarction (LVMI) promotes atrial and pulmonary veins (PV) sympathetic nerve sprouting. Objectives: To test the hypothesis that sympathetic stimulation with tyramine initiates atrial fibrillation (AF) by early afterdepolarization (EAD)-mediated triggered activity at the left atrial PV (LAPV) junction. Methods: LVMI was created in 6 dogs and 6 dogs served as controls. Six to 8 weeks later the activation pattern of the isolated LAPV was optically mapped using dual voltage and intracellular Ca +2 (Ca i 2+)-sensitive epifluorescent dyes before and after tyramine (5 μM) perfusion. Results: Tyramine initiated spontaneous AF in 5 of 6 atria but none in the control group (P < 0.01). The AF was initiated by late phase 3 EAD-mediated triggered activity that arose from the LAPV junction causing functional conduction block in LA, reentry, and AF. The AF was subsequently maintained by mixed reentrant and focal mechanisms. The EADs arose during the late phase 3, when the Ca i 2+ level was 64 ± 12% of the peak systolic Ca i 2+ transient amplitude, a property caused by tyramine's simultaneous shortening of the action potential duration and lengthening of the Ca i 2+ transient duration in the LVMI group but not in the control. Tyrosine hydroxylase and growth associated protein 43 positive nerve sprouts were significantly increased in the sinus node, LAA, and the LSPV in the LVMI group compared to control (P < 0.01). Conclusions: Increased atrial sympathetic nerve sprouts after LVMI makes the LAPV junction susceptible to late phase 3 EAD-mediated triggered and AF during sympathetic stimulation with tyramine.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalJournal of cardiovascular electrophysiology
Issue number4
StatePublished - Apr 1 2012



  • atrial fibrillation
  • calcium transients
  • early afterdepolarization
  • myocardial infarction
  • optical mapping
  • pulmonary veins
  • sympathetic nerve sprouting
  • triggered activity
  • tyramine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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