Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation.
BACKGROUND
Rapid firing within pulmonary vein sleeves frequently initiates atrial fibrillation. The role of the autonomic nervous system in facilitating spontaneous firing is unknown.


OBJECTIVE
The purpose of this study was to determine if autonomic nerve stimulation within canine atrium and pulmonary vein sleeves initiates arrhythmia formation.


METHODS
Extracellular bipolar and intracellular microelectrode recordings were obtained from isolated superfused canine pulmonary veins (N = 28) and right atrium (N = 5) during local autonomic nerve stimulation.


RESULTS
Autonomic nerve stimulation decreased pulmonary vein sleeve action potential duration (APD90 = 160 +/- 17 to 92 +/- 24 ms; P < .01) and initiated rapid (782 +/- 158 bpm) firing from early afterdepolarizations in 22 of 28 pulmonary vein preparations. The initial spontaneous beat had a coupling interval of 97 +/- 26 ms. Failure to induce arrhythmia was associated with a failure to shorten APD90 (151 +/- 18 to 142 +/- 8 ms; P = .39). Muscarinic receptor blockade (atropine: 3.2 x 10(-8) M) prevented APD90 shortening in 8 of 8 preparations and suppressed firing in 6 of 8 preparations, whereas beta1-adrenergic receptor blockade (atenolol: 3.2 x 10(-8) M) suppressed firing in 8 of 8 preparations. Suppression of the Ca transient with ryanodine (10(-5) M) completely suppressed firing in 6 of 6 preparations. Inhibition of forward Na/Ca exchange by a transient increase in [Ca+2]o completely suppressed firing in 4 of 6 preparations. The same stimulus trains produce atropine-suppressed APD90 shortening in superfused right atrial free wall but fail to produce triggered arrhythmia.


CONCLUSIONS
The data demonstrate triggered firing within canine pulmonary veins with combined parasympathetic and sympathetic nerve stimulation. Both an enhanced Ca transient and increased Na/Ca exchange may be required for arrhythmia formation.
Patterson
Eugene
E
University of Oklahoma Health Sciences Center and Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA. eugene-patterson@ouhsc.edu
Po
Sunny S
SS
Scherlag
Benjamin J
BJ
Lazzara
Ralph
R
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000503:physiopathology; D008297:Male; D011667:Pulmonary Veins / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D012433:Ryanodine; D013779:Tetrodotoxin; D001262:Atenolol; D001285:Atropine