Spontaneous atrial fibrillation initiated by tyramine in canine atria with increased sympathetic nerve sprouting.
BACKGROUND
Chronic left ventricular myocardial infarction (LVMI) promotes atrial and pulmonary veins (PV) sympathetic nerve sprouting.


OBJECTIVE
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.
Division of Cardiovascular Medicine, Ohashi Medical Center, Toho University, Tokyo, Japan.
Ayaka
A
Numata
Yasushi
Y
Miyauchi
Norihiko
N
Ono
Michael C
MC
Fishbein
William J
WJ
Mandel
Shien-Fong
SF
Lin
James N
JN
Weiss
Peng-Sheng
PS
Chen
Hrayr S
HS
Karagueuzian
D000200:Action Potentials; D000818:Animals; D020517:Atrial Appendage / Q000294:innervation; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000503:physiopathology; D016279:Atrial Function, Left; D020013:Calcium Signaling; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D006325:Heart Atria / Q000294:innervation; D008297:Male; D012849:Sinoatrial Node / Q000294:innervation; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors; D014439:Tyramine; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D056969:Voltage-Sensitive Dye Imaging
D019922:GAP-43 Protein; D014446:Tyrosine 3-Monooxygenase; D014439:Tyramine