Yutao Xi1, Zhi-Yang James Chao2, Wen Yan2, Shahrzad Abbasi2, Xiaomeng Yin3, Nilesh Mathuria1, Mehul Patel4, Christopher Fan2, Junping Sun2, Geru Wu2, Suwei Wang2, MacArthur Elayda2, Lianjun Gao3, Xander H T Wehrens5, Shien-Fong Lin6, Jie Cheng7. 1. Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Section of Cardiology, University of Texas School of Medicine at Houston, Houston, Texas. 2. Texas Heart Institute/St. Luke's Hospital, Houston, Texas. 3. Dalian Medical University, Dalian, Liaoning, China. 4. Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas. 5. Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas. 6. Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana. Electronic address: jcheng@heart.thi.tmc.edu. 7. 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.
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.
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.
Authors: K Marron; J Wharton; M N Sheppard; D Fagan; D Royston; D M Kuhn; M R de Leval; B F Whitehead; R H Anderson; J M Polak Journal: Circulation Date: 1995-10-15 Impact factor: 29.690
Authors: T W Moody; F Zia; M Draoui; D E Brenneman; M Fridkin; A Davidson; I Gozes Journal: Proc Natl Acad Sci U S A Date: 1993-05-15 Impact factor: 11.205