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
Texas Heart Institute/St. Luke's Hospital, Houston, Texas; Section of Cardiology, University of Texas School of Medicine at Houston, Houston, Texas.
Texas Heart Institute/St. Luke's Hospital, Houston, Texas.
Heart Rhythm. 2015 Jun;12(6):1352-61. doi: 10.1016/j.hrthm.2015.03.003. Epub 2015 Mar 5.
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.
The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation.
We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts.
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.
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.
迷走神经活动亢进会促进心房颤动（AF），这几乎完全归因于乙酰胆碱。血管活性肠肽（VIP）和乙酰胆碱是迷走神经刺激期间共同释放的神经递质。外源性VIP已被证明可通过缩短动作电位时程（APD）、增加APD空间异质性以及导致心房内传导阻滞来促进AF。
本研究旨在探讨迷走神经刺激期间神经元释放的VIP对心房电生理特性的影响。
我们使用一种特异性VIP拮抗剂（H9935）来揭示犬心脏迷走神经刺激期间内源性VIP释放的作用。
H9935显著减弱了（1）在刺激颈迷走交感干（VCNS）期间迷走神经诱导的心房有效不应期缩短和心房易损窗口增宽，以及（2）通过脂肪垫神经节丛（VGPS）刺激期间迷走神经对APD的影响。阿托品在VCNS和VGPS期间完全消除了这些迷走神经效应。相比之下，VIP拮抗剂或阿托品均可完全消除VGPS诱导的局部传导速度减慢。在VGPS期间起搏诱发的AF中，H9935显著降低了最大主导频率及其空间梯度，阿托品的作用更明显。此外，阿托品抑制了迷走神经刺激期间心房内VIP的释放，这可能解释了毒蕈碱阻断时VIP效应的隐匿性。
神经元释放的VIP有助于迷走神经对心房电生理特性的影响，并影响迷走神经诱发AF的病理生理学。毒蕈碱阻断可抑制心房内神经元释放VIP，这是迷走神经刺激期间阿托品隐匿VIP效应的一种新机制。
