<?xml version='1.0' encoding='utf-8'?>
<!--
This CellML file was generated on 25/02/2008 at 13:56:30 using:
COR (0.9.31.873)
Copyright 2002-2008 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="bueno_2007" name="bueno_2007">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model is known to run in both COR and PCEnv to recreate the results of the original model.
</para>
<para>
ValidateCellML verifies this model as valid CellML with fully consistent units.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Modeling the dynamics of electrical wave propagation in cardiac tissue requires the use of appropriate ionic models capable to reproduce the key characteristics of this type of systems, suitable fitted for the specie under study. In the current study Alfonso Bueno presents a new minimal model for human ventricular action potentials which is able to accurately reproduce a range of experimentally measured characteristics of cardiac tissue, including threshold for excitation, action potential morphology, rate of rise, and rate dependence properties (action potential duration and conduction velocity) for epicardial, endocardial and midmyocardial cells. Since the number of parameters involved is significantly smaller than in other models, it is easier to understand the role that each parameter plays in each of the above mentioned characteristics, therefore making substantially easier to obtain fittings for different data. Besides, in terms of computational efficiency the new model can be simulated several orders of magnitude faster than other human ventricular models, which makes the new model especially suitable for large scale and whole organ simulations.
</para>
<para>
The applicability and usefulness of the new model have been proved by addressing the study of the Brugada syndrome, an important hereditary genetic disease able to cause sudden cardiac death in human patients even without identifiable structural abnormalities. Despite not incorporating independent descriptions for each of the known currents measured through the cell membrane, the model is however capable to correctly reproduce both the healthy and pathological conditions of the epicardial tissue layer, the latter being characterized by the presence of a much deeper notch in the cardiac action potential as a result of a loss of functionality of sodium channels which leaves unopposed the transient outward potassium current.
</para>
<para>
Despite being able of reproducing a great amount of available experimental data, one important limitation of the proposed minimal model is that it lacks of a complete description of intracellular calcium dynamics. Hence, the model cannot be used to study particular conditions of importance in the generation and development of arrhythmias, such as calcium overload, spontaneous calcium release or calcium-induced alternans. This limitation could be overcome however by coupling our simplified model of the cardiac transmembrane potential to a reduced model of the intracellular calcium cycling of the ventricular myocyte, such as the one suggested by Shiferaw et al. (2003), therefore yielding the first implementation of a second-generation simplified ionic model of the cardiac myocyte.
</para>
<!--
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<title>model diagram</title>
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<caption>A schematic diagram of ...</caption>
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-->
<para>
This model was taken from the PhD thesis of Alfonso Bueno:
</para>
<para>
Mathematical modeling and spectral simulation of genetic diseases in the human heart, Alfonso Bueno, Department of Mathematics, University of Castilla-La Mancha, Ciudad Real, May 2007.
</para>
</sect1> -->
</article>
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<dc:title>Mathematical modeling and spectral simulation of genetic diseases in the human heart</dc:title>
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<vCard:Orgname>The University of Oxford</vCard:Orgname>
<vCard:Orgunit>Department of Physiology, Anatomy & Genetics</vCard:Orgunit>
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<rdf:Description rdf:about="rdf:#0b09c387-f86a-4586-8e47-8f493a62f324">
<vCard:Given>Penny</vCard:Given>
<vCard:Family>Noble</vCard:Family>
<vCard:Other/>
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<vCard:N rdf:resource="rdf:#0b09c387-f86a-4586-8e47-8f493a62f324"/>
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<rdf:Description rdf:about="rdf:#0e6ae837-14b7-41fc-bea4-c1bb9aa16225">
<dcterms:W3CDTF>2007-05-00 00:00</dcterms:W3CDTF>
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<dc:creator rdf:resource="rdf:#48ebd61a-83c5-44df-9400-4c2b3a81fb6b"/>
<rdf:value>This CellML model is known to run in both COR and PCEnv to recreate the results of the original model. The units have been checked and are consistent. Model has been curated using Bueno 2007 thesis.</rdf:value>
</rdf:Description>
</rdf:RDF>
</model>
