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


CONCLUSIONS
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.
Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Section of Cardiology, University of Texas School of Medicine at Houston, Houston, Texas.
Yutao
Y
Xi
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Zhi-Yang
ZY
James Chao
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Wen
W
Yan
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Shahrzad
S
Abbasi
Dalian Medical University, Dalian, Liaoning, China.
Xiaomeng
X
Yin
Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Section of Cardiology, University of Texas School of Medicine at Houston, Houston, Texas.
Nilesh
N
Mathuria
Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas.
Mehul
M
Patel
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Christopher
C
Fan
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Junping
J
Sun
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Geru
G
Wu
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Suwei
S
Wang
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
MacArthur
M
Elayda
Dalian Medical University, Dalian, Liaoning, China.
Lianjun
L
Gao
Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas.
Xander H T
XH
Wehrens
Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana. Electronic address: jcheng@heart.thi.tmc.edu.
Shien-Fong
SF
Lin
Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Section of Cardiology, University of Texas School of Medicine at Houston, Houston, Texas. Electronic address: linsf@iupui.edu.
Jie
J
Cheng
D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology*; D016275:Atrial Function / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D009116:Muscarine / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D055536:Vagus Nerve Stimulation; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*
D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D009116:Muscarine
Atrial fibrillation; Vagal stimulation; Vasoactive intestinal polypeptide