TY - JOUR
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
N1 - Funding Information:
This work was supported in part by American Heart Association Grants 11GRNT8000093 to Dr. Cheng and 13EIA14560061 to Dr. Wehrens; and National Institute of Health Grants R01-HL089598 and R01-HL117641 to Dr. Wehrens. This work was presented in part at the 34th Annual Scientific Sessions of the Heart Rhythm Society, May 8–11, 2013, Denver, Colorado.
Publisher Copyright:
© 2015 Heart Rhythm Society.
PY - 2015/6/1
Y1 - 2015/6/1
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.
KW - Atrial fibrillation
KW - Vagal stimulation
KW - Vasoactive intestinal polypeptide
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U2 - 10.1016/j.hrthm.2015.03.003
DO - 10.1016/j.hrthm.2015.03.003
M3 - Article
C2 - 25748673
AN - SCOPUS:84930361968
VL - 12
SP - 1352
EP - 1361
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 6
ER -