Inducibility of atrial fibrillation after GP ablations and "autonomic blockade": evidence for the pathophysiological role of the nonadrenergic and noncholinergic neurotransmitters.
BACKGROUND
Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility.


METHODS
In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac-Tyr1,D-phe2]-VIP).


RESULTS
GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist.


CONCLUSIONS
Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and "autonomic blockade," which may further define the substrate for AF outside the pulmonary vein-atrial junctions.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Yu
Y
Liu
Benjamin J
BJ
Scherlag
Youqi
Y
Fan
Vandana
V
Varma
Shailesh
S
Male
Muhammad A
MA
Chaudhry
Congxin
C
Huang
Sunny S
SS
Po
D059331:Adrenergic Neurons / Q000378:metabolism; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D001341:Autonomic Nervous System / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000378:metabolism; D004285:Dogs; D045888:Ganglion Cysts / Q000378:metabolism*; D006329:Heart Conduction System / Q000378:metabolism*; D009415:Nerve Net / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*
D018377:Neurotransmitter Agents