Inducibility of atrial fibrillation after GP ablations and "autonomic blockade": Evidence for the pathophysiological role of the nonadrenergic and noncholinergic neurotransmitters

Yu Liu, Benjamin J. Scherlag, Youqi Fan, Vandana Varma, Shailesh Male, Muhammad A. Chaudhry, Congxin Huang, Sunny S. Po

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Autonomic Blockade and Atrial Fibrillation. 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.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalJournal of cardiovascular electrophysiology
Volume24
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • atrial fibrillation
  • autonomic nervous system
  • ganglionic plexus
  • neurotransmittors
  • sympathetic nervous system
  • vagus

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