Document Detail

Spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic nerve sprouting.
MedLine Citation:
PMID:  22034958     Owner:  NLM     Status:  MEDLINE    
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 after depolarization (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.
Ayaka Numata; Yasushi Miyauchi; Norihiko Ono; Michael C Fishbein; William J Mandel; Shien-Fong Lin; James N Weiss; Peng-Sheng Chen; Hrayr S Karagueuzian
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-28
Journal Detail:
Title:  Journal of cardiovascular electrophysiology     Volume:  23     ISSN:  1540-8167     ISO Abbreviation:  J. Cardiovasc. Electrophysiol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-08-13     Revised Date:  2013-04-12    
Medline Journal Info:
Nlm Unique ID:  9010756     Medline TA:  J Cardiovasc Electrophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-22     Citation Subset:  IM    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
Division of Cardiovascular Medicine, Ohashi Medical Center, Toho University, Tokyo, Japan.
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MeSH Terms
Action Potentials
Atrial Appendage / innervation
Atrial Fibrillation / chemically induced*,  physiopathology
Atrial Function, Left*
Calcium Signaling
Disease Models, Animal
GAP-43 Protein / metabolism
Heart / innervation*
Heart Atria / innervation
Sinoatrial Node / innervation
Sympathetic Nervous System / physiopathology*
Time Factors
Tyrosine 3-Monooxygenase / metabolism
Voltage-Sensitive Dye Imaging
Grant Support
Reg. No./Substance:
0/GAP-43 Protein; 51-67-2/Tyramine; EC 3-Monooxygenase

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