This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olgin, J. E. Articles by Hutchins, G. Search for Related Content PubMed PubMed Citation Articles by Olgin, J. E. Articles by Hutchins, G. Pubmed/NCBI databases Medline Plus Health Information Atrial Fibrillation

(Circulation. 1998;98:2608-2614.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

Jeffrey E. Olgin, MD; Haris J. Sih, PhD; Steven Hanish, MS; J. Vijay Jayachandran, MD; Jiashin Wu, PhD; Qi Huang Zheng, PhD; Wendy Winkle; G. Keith Mulholland, PhD; Douglas P. Zipes, MD; Gary Hutchins, PhD

From the Krannert Institute of Cardiology, Department of Medicine (J.E.O., H.J.S., S.H., J.V.J., J.W., D.P.Z.), and the Department of Radiology (Q.H.Z., W.W., G.K.M., G.H.), Indiana University School of Medicine, Indianapolis.

Correspondence to Jeffrey E. Olgin, MD, Krannert Institute of Cardiology, Indiana University School of Medicine, 1111 W 10th St, Indianapolis, IN 46202-4800. E-mail jolgin{at}iupui.edu

Background—Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF.

Methods and Results—After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation. Dogs then underwent PET imaging with either a sympathetic ([¹¹C]hydroxyephedrine, HED) or parasympathetic (5-[¹¹C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (>60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136±17.6 ms) than those same sites in the sham controls (156±19.1 ms) (P=0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17±8%) than in the nonphenol sites (9±9%) (P=0.01). There was a significantly increased dispersion of refractoriness (21±6.4 ms in the sham versus 58±14 ms in the phenol dogs, P=0.01) as well as dispersion of AF cycle length (49±10 ms in the sham versus 105±12 ms in the phenol dogs, P=0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake.

Conclusions—Heterogeneous sympathetic atrial denervation with phenol facilitates sustained AF.

Key Words: fibrillation • nervous system, autonomic • phenol • tomography • hydroxyephedrine

This article has been cited by other articles:

				A. Y. Tan, S. Zhou, M. Ogawa, J. Song, M. Chu, H. Li, M. C. Fishbein, S.-F. Lin, L. S. Chen, and P.-S. Chen Neural Mechanisms of Paroxysmal Atrial Fibrillation and Paroxysmal Atrial Tachycardia in Ambulatory Canines Circulation, August 26, 2008; 118(9): 916 - 925. [Abstract] [Full Text] [PDF]

				R. Arora, J. S. Ulphani, R. Villuendas, J. Ng, L. Harvey, S. Thordson, F. Inderyas, Y. Lu, D. Gordon, P. Denes, et al. Neural substrate for atrial fibrillation: implications for targeted parasympathetic blockade in the posterior left atrium Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H134 - H144. [Abstract] [Full Text] [PDF]

				M. Scanavacca, C. F. Pisani, D. Hachul, S. Lara, C. Hardy, F. Darrieux, I. Trombetta, C. E. Negrao, and E. Sosa Selective Atrial Vagal Denervation Guided by Evoked Vagal Reflex to Treat Patients With Paroxysmal Atrial Fibrillation Circulation, August 29, 2006; 114(9): 876 - 885. [Abstract] [Full Text] [PDF]

				Y. Takahashi, P. Jais, M. Hocini, P. Sanders, M. Rotter, T. Rostock, L.-F. Hsu, F. Sacher, J. Clementy, and M. Haissaguerre Shortening of Fibrillatory Cycle Length in the Pulmonary Vein During Vagal Excitation J. Am. Coll. Cardiol., February 21, 2006; 47(4): 774 - 780. [Abstract] [Full Text] [PDF]

				K. Matsuura, H. Ogino, H. Matsuda, K. Minatoya, H. Sasaki, A. Kada, T. Yagihara, and S. Kitamura Prediction and Incidence of Atrial Fibrillation After Aortic Arch Repair Ann. Thorac. Surg., February 1, 2006; 81(2): 514 - 518. [Abstract] [Full Text] [PDF]

				S. Vikman, K. Lindgren, T. H. Makikallio, S. Yli-Mayry, K.E. J. Airaksinen, and H. V. Huikuri Heart rate turbulence after atrial premature beats before spontaneous onset of atrial fibrillation J. Am. Coll. Cardiol., January 18, 2005; 45(2): 278 - 284. [Abstract] [Full Text] [PDF]

				W. H. Maisel Autonomic modulation preceding the onset of atrial fibrillation J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1269 - 1270. [Full Text] [PDF]

				Y. Miyauchi, S. Zhou, Y. Okuyama, M. Miyauchi, H. Hayashi, A. Hamabe, M. C. Fishbein, W. J. Mandel, L. S. Chen, P.-S. Chen, et al. Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction: Implications for Atrial Fibrillation Circulation, July 22, 2003; 108(3): 360 - 366. [Abstract] [Full Text] [PDF]

				I. R. Efimov Fibrillation or Neurillation: Back to the Future in Our Concepts of Sudden Cardiac Death? Circ. Res., May 30, 2003; 92(10): 1062 - 1064. [Full Text] [PDF]

				C. Dimmer, T. Szili-Torok, R. Tavernier, T. Verstraten, and L. J. Jordaens Initiating mechanisms of paroxysmal atrial fibrillation Europace, January 1, 2003; 5(1): 1 - 9. [Abstract] [PDF]

				M. Rubart and D. P. Zipes NO Hope for Patients With Atrial Fibrillation Circulation, November 26, 2002; 106(22): 2764 - 2766. [Full Text] [PDF]

				J. E. Olgin and S. Verheule Transgenic and knockout mouse models of atrial arrhythmias Cardiovasc Res, May 1, 2002; 54(2): 280 - 286. [Abstract] [Full Text] [PDF]

				P. Kovoor, K. Wickman, C. T. Maguire, W. Pu, J. Gehrmann, C. I. Berul, and D. E. Clapham Evaluation of the role of IKACh in atrial fibrillation using a mouse knockout model J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2136 - 2143. [Abstract] [Full Text] [PDF]

				C.-M. Chang, T.-J. Wu, S. Zhou, R. N. Doshi, M.-H. Lee, T. Ohara, M. C. Fishbein, H. S. Karagueuzian, P.-S. Chen, and L. S. Chen Nerve Sprouting and Sympathetic Hyperinnervation in a Canine Model of Atrial Fibrillation Produced by Prolonged Right Atrial Pacing Circulation, January 2, 2001; 103(1): 22 - 25. [Abstract] [Full Text] [PDF]

				D. Amar, N. Roistacher, V. W. Rusch, D. H. Y. Leung, I. Ginsburg, H. Zhang, M. S. Bains, R. J. Downey, R. J. Korst, and R. J. Ginsberg Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 790 - 798. [Abstract] [Full Text] [PDF]

				J. V. Jayachandran, H. J. Sih, W. Winkle, D. P. Zipes, G. D. Hutchins, and J. E. Olgin Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation Circulation, March 14, 2000; 101(10): 1185 - 1191. [Abstract] [Full Text] [PDF]

				H. Ramanna, R. N. W. Hauer, F. H. M. Wittkampf, J. M. T. de Bakker, E. F. D. Wever, A. Elvan, and E. O. Robles de Medina Identification of the Substrate of Atrial Vulnerability in Patients With Idiopathic Atrial Fibrillation Circulation, March 7, 2000; 101(9): 995 - 1001. [Abstract] [Full Text] [PDF]