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

Yutao Xi, Zhi Yang James Chao, Wen Yan, Shahrzad Abbasi, Xiaomeng Yin, Nilesh Mathuria, Mehul Patel, Christopher Fan, Junping Sun, Geru Wu, Suwei Wang, Macarthur Elayda, Lianjun Gao, Xander H.T. Wehrens, Shien Fong Lin, Jie Cheng

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1352-1361
Number of pages10
JournalHeart Rhythm
Volume12
Issue number6
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Vasoactive Intestinal Peptide
Atrial Fibrillation
Atropine
Action Potentials
Cholinergic Agents
Acetylcholine
Ganglia
Neurotransmitter Agents
Canidae
Adipose Tissue

Keywords

  • Atrial fibrillation
  • Vagal stimulation
  • Vasoactive intestinal polypeptide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation. / Xi, Yutao; James Chao, Zhi Yang; Yan, Wen; Abbasi, Shahrzad; Yin, Xiaomeng; Mathuria, Nilesh; Patel, Mehul; Fan, Christopher; Sun, Junping; Wu, Geru; Wang, Suwei; Elayda, Macarthur; Gao, Lianjun; Wehrens, Xander H.T.; Lin, Shien Fong; Cheng, Jie.

In: Heart Rhythm, Vol. 12, No. 6, 01.01.2015, p. 1352-1361.

Research output: Contribution to journalArticle

Xi, Y, James Chao, ZY, Yan, W, Abbasi, S, Yin, X, Mathuria, N, Patel, M, Fan, C, Sun, J, Wu, G, Wang, S, Elayda, M, Gao, L, Wehrens, XHT, Lin, SF & Cheng, J 2015, 'Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation', Heart Rhythm, vol. 12, no. 6, pp. 1352-1361. https://doi.org/10.1016/j.hrthm.2015.03.003
Xi, Yutao ; James Chao, Zhi Yang ; Yan, Wen ; Abbasi, Shahrzad ; Yin, Xiaomeng ; Mathuria, Nilesh ; Patel, Mehul ; Fan, Christopher ; Sun, Junping ; Wu, Geru ; Wang, Suwei ; Elayda, Macarthur ; Gao, Lianjun ; Wehrens, Xander H.T. ; Lin, Shien Fong ; Cheng, Jie. / Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation. In: Heart Rhythm. 2015 ; Vol. 12, No. 6. pp. 1352-1361.
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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.",
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T1 - Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation

AU - Xi, Yutao

AU - James Chao, Zhi Yang

AU - Yan, Wen

AU - Abbasi, Shahrzad

AU - Yin, Xiaomeng

AU - Mathuria, Nilesh

AU - Patel, Mehul

AU - Fan, Christopher

AU - Sun, Junping

AU - Wu, Geru

AU - Wang, Suwei

AU - Elayda, Macarthur

AU - Gao, Lianjun

AU - Wehrens, Xander H.T.

AU - Lin, Shien Fong

AU - Cheng, Jie

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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