Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 2005;111:846-854
Published online before print February 7, 2005, doi: 10.1161/01.CIR.0000152100.04087.DB
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
111/7/846    most recent
01.CIR.0000152100.04087.DBv1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dobrzynski, H.
Right arrow Articles by Boyett, M.R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dobrzynski, H.
Right arrow Articles by Boyett, M.R.
Related Collections
Right arrow Structure
Right arrow Other myocardial biology
Right arrow Pacemaker
Right arrow Ion channels/membrane transport
Right arrow 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 {approx}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:


Home page
Physiol. Rev.Home page
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]


Home page
Circ. Res.Home page
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]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
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]


Home page
Circ. Res.Home page
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]


Home page
CirculationHome page
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]


Home page
Cardiovasc ResHome page
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]


Home page
Circ. Res.Home page
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]


Home page
Cardiovasc ResHome page
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]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
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]


Home page
Exp PhysiolHome page
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]


Home page
J. Physiol.Home page
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]