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The Scientific World Journal
Volume 2014, Article ID 540496, 11 pages
Research Article

Isoprenaline: A Potential Contributor in Sick Sinus Syndrome—Insights from a Mathematical Model of the Rabbit Sinoatrial Node

1Department of Physics and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen 361005, China
2College of Physics and Electronic Information, Anhui Normal University, Wuhu 241000, China
3Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester M139PL, UK

Received 24 October 2013; Accepted 3 December 2013; Published 21 January 2014

Academic Editors: C. Carbucicchio and K. W. Lobdell

Copyright © 2014 Xiang Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca2+ transient, and changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase in and which were reduced by the mutation.