Low level tragus nerve stimulation is a non-invasive approach for anti-atrial fibrillation via preventing the loss of connexins

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the mechanism of AF maintenance remains unclear. It has been found that gap junctional remodeling (connexin expression is downregulated and distributed) is closely associated with AF maintenance [ [1] Van der Velden H.M. Ausma J. Rook M.B. Hellemons A.J. van Veen T.A. Allessie M.A. Jongsma H.J. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc. Res. 2000; 46: 476-486 Crossref PubMed Scopus (214) Google Scholar ]. Autonomic nervous system stimulation can exert anti-arrhythmia effects [ 2 Thunsiri K. Shinlapawittayatorn K. Chinda K. Palee S. Surinkaew S. Chattipakorn S.C. KenKnight B.H. Chattipakorn N. Application of vagus nerve stimulation from the onset of ventricular fibrillation to post-shock period improves defibrillation efficacy. Int. J. Cardiol. 2014; 176: 1030-1032 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 3 He B. Lu Z. He W. Huang B. Jiang H. Similar effects of vagus nerve stimulation and atrial ganglionated plexi stimulation on ventricular effective refractory period and action potential duration in canine. Int. J. Cardiol. 2013; 168: 5116-5118 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. Recently, we reported that cervical low level vagal nerve stimulation (LL-VNS) could suppress AF induced high-frequency stimulation [ [4] Yu L. Scherlag B.J. Li S. Sheng X. Lu Z. Nakagawa H. Zhang Y. Jackman W.M. Lazzara R. Jiang H. Po S.S. Low-level vagosympathetic nerve stimulation inhibits atrial fibrillation inducibility: direct evidence by neural recordings from intrinsic cardiac ganglia. J. Cardiovasc. Electrophysiol. 2011; 22: 455-463 Crossref PubMed Scopus (104) Google Scholar ] and then we developed a non-invasive approach, low level tragus nerve stimulation (LL-TS), and found that it had the same effect on suppressing AF [ [5] Yu L. Scherlag B.J. Li S. Fan Y. Dyer J. Male S. Varma V. Sha Y. Stavrakis S. Po S.S. Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve: a noninvasive approach to treat the initial phase of atrial fibrillation. Heart Rhythm. 2013; 10: 428-435 Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar ]. However, whether LL-TS could regulate Cx40 and Cx43 to suppress AF remains unknown. We hypothesized that LL-TS exerted anti-atrial fibrillatory effect via the downregulation of atrial Cx40 and Cx43.