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- Title
Spontaneous Atrial Fibrillation Initiated by Tyramine in Canine Atria with Increased Sympathetic Nerve Sprouting.
- Authors
NUMATA, AYAKA; MIYAUCHI, YASUSHI; ONO, NORIHIKO; FISHBEIN, MICHAEL C.; MANDEL, WILLIAM J.; LIN, SHIEN‐FONG; WEISS, JAMES N.; CHEN, PENG‐SHENG; KARAGUEUZIAN, HRAYR S.
- Abstract
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 (Cai2+)-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 Cai2+ level was 64 ± 12% of the peak systolic Cai2+ transient amplitude, a property caused by tyramine's simultaneous shortening of the action potential duration and lengthening of the Cai2+ 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.
- Subjects
ANALYSIS of variance; ANIMAL experimentation; ATRIAL fibrillation; BIOPHYSICS; CALCIUM; DOGS; FISHER exact test; LEFT heart ventricle; HEART atrium; IMMUNOHISTOCHEMISTRY; RESEARCH methodology; MYOCARDIAL infarction; NEUROPHYSIOLOGY; RESEARCH funding; STATISTICAL hypothesis testing; SYMPATHETIC nervous system; SYMPATHOMIMETIC agents; T-test (Statistics); TISSUE culture; DESCRIPTIVE statistics
- Publication
Journal of Cardiovascular Electrophysiology, 2012, Vol 23, Issue 4, p415
- ISSN
1045-3873
- Publication type
Article
- DOI
10.1111/j.1540-8167.2011.02197.x