This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 111/7/846    most recent 01.CIR.0000152100.04087.DBv1 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 Dobrzynski, H. Articles by Boyett, M.R. Search for Related Content PubMed PubMed Citation Articles by Dobrzynski, H. Articles by Boyett, M.R. Related Collections Structure Other myocardial biology Pacemaker Ion channels/membrane transport Quantitative modeling

(Circulation. 2005;111:846-854.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Computer Three-Dimensional Reconstruction of the Sinoatrial Node

H. Dobrzynski, PhD^*; J. Li, PhD^*; J. Tellez, BSc; I.D. Greener, BSc; V.P. Nikolski, PhD; S.E. Wright, MD; S.H. Parson, PhD; S.A. Jones, PhD; M.K. Lancaster, PhD; M. Yamamoto, MD; H. Honjo, MD; Y. Takagishi, PhD; I. Kodama, MD; I.R. Efimov, PhD; R. Billeter, PhD; M.R. Boyett, PhD

From the University of Leeds, Leeds, UK (H.D., J.L., J.T., I.D.G., S.E.W., S.H.P., S.A.J., M.K.L., M.Y., R.B., M.R.B.); Washington University, St Louis, Mo (V.P.N., I.R.E.); and Nagoya University, Nagoya, Japan (H.H., Y.T., I.K.).

Correspondence to Dr H. Dobrzynski, University of Leeds, Leeds LS2 9JT, UK. E-mail bmshd{at}leeds.ac.uk

Received August 18, 2004; revision received September 13, 2004; accepted September 29, 2004.

Background— There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features.

Methods and Results— Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An 2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed.

Conclusions— For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.

Key Words: sinoatrial node • pacemakers • imaging, three-dimensional • models, theoretical • computer simulation

This article has been cited by other articles:

				M. R. Boyett \#8216;And the beat goes on' The cardiac conduction system: the wiring system of the heart Exp Physiol, October 1, 2009; 94(10): 1035 - 1049. [Abstract] [Full Text] [PDF]

				V. V. Fedorov, R. B. Schuessler, M. Hemphill, C. M. Ambrosi, R. Chang, A. S. Voloshina, K. Brown, W. J. Hucker, and I. R. Efimov Structural and Functional Evidence for Discrete Exit Pathways That Connect the Canine Sinoatrial Node and Atria Circ. Res., April 10, 2009; 104(7): 915 - 923. [Abstract] [Full Text] [PDF]

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]

				J. Li, I. D. Greener, S. Inada, V. P. Nikolski, M. Yamamoto, J. C. Hancox, H. Zhang, R. Billeter, I. R. Efimov, H. Dobrzynski, et al. Computer Three-Dimensional Reconstruction of the Atrioventricular Node Circ. Res., April 25, 2008; 102(8): 975 - 985. [Abstract] [Full Text] [PDF]

				M. Baruscotti and R. B. Robinson Electrophysiology and pacemaker function of the developing sinoatrial node Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2613 - H2623. [Abstract] [Full Text] [PDF]

				A. E. Lyashkov, M. Juhaszova, H. Dobrzynski, T. M. Vinogradova, V. A. Maltsev, O. Juhasz, H. A. Spurgeon, S. J. Sollott, and E. G. Lakatta Calcium Cycling Protein Density and Functional Importance to Automaticity of Isolated Sinoatrial Nodal Cells Are Independent of Cell Size Circ. Res., June 22, 2007; 100(12): 1723 - 1731. [Abstract] [Full Text] [PDF]

				H. Dobrzynski, M. R. Boyett, and R. H. Anderson New Insights Into Pacemaker Activity: Promoting Understanding of Sick Sinus Syndrome Circulation, April 10, 2007; 115(14): 1921 - 1932. [Full Text] [PDF]

				J. Liu, H. Dobrzynski, J. Yanni, M. R. Boyett, and M. Lei Organisation of the mouse sinoatrial node: structure and expression of HCN channels Cardiovasc Res, March 1, 2007; 73(4): 729 - 738. [Abstract] [Full Text] [PDF]

				J. O. Tellez, H. Dobrzynski, I. D. Greener, G. M. Graham, E. Laing, H. Honjo, S. J. Hubbard, M. R. Boyett, and R. Billeter Differential Expression of Ion Channel Transcripts in Atrial Muscle and Sinoatrial Node in Rabbit Circ. Res., December 8, 2006; 99(12): 1384 - 1393. [Abstract] [Full Text] [PDF]

				M. Yamamoto, H. Dobrzynski, J. Tellez, R. Niwa, R. Billeter, H. Honjo, I. Kodama, and M. R. Boyett Extended atrial conduction system characterised by the expression of the HCN4 channel and connexin45 Cardiovasc Res, November 1, 2006; 72(2): 271 - 281. [Abstract] [Full Text] [PDF]

				V. V. Fedorov, W. J. Hucker, H. Dobrzynski, L. V. Rosenshtraukh, and I. R. Efimov Postganglionic nerve stimulation induces temporal inhibition of excitability in rabbit sinoatrial node Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H612 - H623. [Abstract] [Full Text] [PDF]

				G. Seemann, C. Hoper, F. B Sachse, O. Dossel, A. V Holden, and H. Zhang Heterogeneous three-dimensional anatomical and electrophysiological model of human atria Phil Trans R Soc A, June 15, 2006; 364(1843): 1465 - 1481. [Abstract] [Full Text] [PDF]

				M. L. Trew, B. J. Caldwell, G. B. Sands, D. A. Hooks, D. C.-S. Tai, T. M. Austin, I. J. LeGrice, A. J. Pullan, and B. H. Smaill Cardiac electrophysiology and tissue structure: bridging the scale gap with a joint measurement and modelling paradigm Exp Physiol, March 1, 2006; 91(2): 355 - 370. [Abstract] [Full Text] [PDF]

				M. Lei, C. Goddard, J. Liu, A.-L. Leoni, A. Royer, S. S.-M. Fung, G. Xiao, A. Ma, H. Zhang, F. Charpentier, et al. Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a J. Physiol., September 1, 2005; 567(2): 387 - 400. [Abstract] [Full Text] [PDF]