Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation

Heart Rhythm. 2015 Jun;12(6):1352-61. doi: 10.1016/j.hrthm.2015.03.003. Epub 2015 Mar 5.

Abstract

Background: Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block.

Objective: The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation.

Methods: We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts.

Results: H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade.

Conclusion: Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation.

Keywords: Atrial fibrillation; Vagal stimulation; Vasoactive intestinal polypeptide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Atrial Fibrillation / etiology*
  • Atrial Function / physiology*
  • Atropine / pharmacology
  • Dogs
  • Muscarine / pharmacology
  • Refractory Period, Electrophysiological / drug effects
  • Vagus Nerve Stimulation*
  • Vasoactive Intestinal Peptide / antagonists & inhibitors
  • Vasoactive Intestinal Peptide / metabolism*
  • Vasoactive Intestinal Peptide / physiology*

Substances

  • Vasoactive Intestinal Peptide
  • Atropine
  • Muscarine