<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : mlcek_model_2001_version02.xml
CREATED : 23rd May 2007
LAST MODIFIED : 23rd May 2007
AUTHOR : Catherine Lloyd
The Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Mlcek et al's
mathematical model of the electromechanical heart contractile
system.
CHANGES:
--><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:pathway_editor="http://www.physiome.com/pathway_editor/1.0#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" pathway_editor:rendering_config_file="mlcek_model_2001_CellMLrender.xml" cmeta:id="mlcek_model_2001_version02" name="mlcek_neumann_kittnar_novak_2001_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Mathematical Model of the Electromechanical Heart Contractile System</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Computational modelling in molecular cardiology has recently focused on simulating subsets of myocardial excitation-contraction processes. As people try to improve their understanding of myocardial function, there is an increasing interest in excitation-contraction coupling and mechanical events in cardiac muscle. It is hoped that these computer simulations will also help explain the pathophysiological mechanisms of heart failure.
</para>
<para>
In their 2001 paper, Mlcek, Neumann, Kittnar and Novak concentrate on the molecular level of electromechanical events in cardiac muscle. They introduce an actomyosin subsystem accompanied by a simple regulatory subsystem involving calcium binding to troponin C (see <xref linkend="fig_reaction_diagram"/> below). They performed many simulations to prove the stability of their model and they then used the simulation results to help interpret experimental and clinical data.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.biomed.cas.cz/physiolres/2001/issue4/mlcek.htm">Mathematical Model of the Electromechanical Heart Contractile System - Regulatory Subsystem Physiological Considerations</ulink>, M. Mlcek, J. Neumann, O. Kittnar and V. Novak, 2001, <ulink url="http://www.biomed.cas.cz/physiolres/">
<emphasis>Physiological Research</emphasis>
</ulink>, 50, 425-432. (A PDF version of the article is also available on the Physiological Research journal website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11551150&dopt=Abstract">PubMed ID: 11551150</ulink>
</para>
<para>
The raw CellML descriptions of the model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram</title>
</objectinfo>
<imagedata fileref="mlcek_2001.png"/>
</imageobject>
</mediaobject>
<caption>Diagram of the regulatory subsystem scheme and the actomyosin subsystem scheme.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<connection>
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<map_variables variable_2="kTA_" variable_1="kTA_"/>
<map_variables variable_2="kDPA" variable_1="kDPA"/>
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<connection>
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<connection>
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<connection>
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<connection>
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<connection>
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<map_variables variable_2="w6" variable_1="w6"/>
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<connection>
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<connection>
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<map_variables variable_2="kr" variable_1="kr"/>
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<rdf:li>Cardiac Myocyte</rdf:li>
<rdf:li>electrophysiology</rdf:li>
<rdf:li>myofilament mechanics</rdf:li>
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<dc:title>A_M_ADP_Pi</dc:title>
</rdf:Description>
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<dc:title>A</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#mlcek_model_2001_version02">
<dc:title>
Mlcek et al's 2001 mathematical model of the elctromechanical heart
contractile system
</dc:title>
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<cmeta:species>Homo sapiens</cmeta:species>
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<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
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<dcterms:alternative>Troponin C</dcterms:alternative>
<dc:title>TnC</dc:title>
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<vCard:Given>Catherine</vCard:Given>
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<vCard:Given>J</vCard:Given>
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<dcterms:alternative>Myosin-ATP</dcterms:alternative>
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<rdf:Description rdf:about="/Cai">
<dcterms:alternative>intracellular free calcium</dcterms:alternative>
<dc:title>Cai</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0b7b5afb-abbf-4729-ba79-9d1cada54283">
<dcterms:W3CDTF>2007-06-05T09:45:51+12:00</dcterms:W3CDTF>
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<dcterms:modified rdf:resource="rdf:#0b7b5afb-abbf-4729-ba79-9d1cada54283"/>
<rdf:value>The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
The model does not run in the PCEnv simulator because it is underconstrained. I have contacted the authors of the original publication and I have requested the parameter values.</rdf:value>
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<vCard:Given>V</vCard:Given>
<vCard:Family>Novak</vCard:Family>
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<dcterms:alternative>Actin-Myosin-ATP</dcterms:alternative>
<dc:title>A_M_ATP</dc:title>
</rdf:Description>
<rdf:Description rdf:about="/CaF">
<dcterms:alternative>sarcoplasmic reticulum calcium</dcterms:alternative>
<dc:title>CaF</dc:title>
</rdf:Description>
<rdf:Description rdf:about="/AM_ADP">
<dcterms:alternative>Actomyosin-ADP</dcterms:alternative>
<dc:title>AM_ADP</dc:title>
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<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<vCard:Given>O</vCard:Given>
<vCard:Family>Kittnar</vCard:Family>
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<rdf:value>Below is a CellML description of Mlcek et al's mathematical model of
the elctromechanical heart contractile system.
Rate constants for the reactions were not specified in the original
paper, therefore in the CellML description they have been set at a
default value of 1.0. Similarly, initial concentrations were not
defined so these have been set at a default value of 1 micromolar.</rdf:value>
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