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<!--  FILE :  bental_model_B_2005.xml

VERSION 2 VARIANT 1

CREATED :  24th December 2004

LAST MODIFIED : 27th April 2005

AUTHOR :  Catherine Lloyd
          The Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Alona Ben-Tal's 2005 mathematical model for a human, flexible lung.

CHANGES:
    27/04/2005 - PJV - Removed undefined initial values.   
   
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Simplified Models For Gas Exchange In The Human Lungs</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>
Data from several different experiments suggest that complex interactions between the respiratory system and cardiac output exist in humans.  Such interactions include the synchronisation between lung ventilation rate and the heart beat, and other examples.  Mathematical models to describe the mechanisms underlying these interactions are being developed with the aim of improving our understanding of these physiological phenomena.
</para>

<para>
Historically, gas exchange in the lungs has been modelled and studied at various different levels of detail.  The 2005 paper by Alona Ben-Tal described here presents a hierarchy of models of increasing complexity for gas exchange in the human lungs:
</para>
<itemizedlist>
  <listitem>
            <para>Model A: The first model represents the lung as an inflexible, single compartment (see <xref linkend="model_A_diagram"/> below);</para>
          </listitem>
  <listitem>
            <para>Model B: The second model represents the lung as a flexible, single compartment (see <xref linkend="model_B_diagram"/> below);</para>
          </listitem>
  <listitem>
            <para>Model C: The third model represents the lung as a flexible, single compartment with gas exchange (see <xref linkend="model_C_diagram"/> below); and </para>
          </listitem>
  <listitem>
            <para>Model D: The final model represents the respiratory system as a flexible, multi-compartmental model with gas exchange and gas transport (see <xref linkend="model_D_diagram"/> below).</para>
          </listitem>
</itemizedlist>

<para>
The models developed in this paper provide a mathematical framework which is able to link together molecular scale and whole systems scale models.  As an integral part of developing this framework, two commonly made assumptions have been re-examined: 
</para>
<itemizedlist>
  <listitem>
            <para>1) the hidden assumption that air flow through the mouth is equal to the rate of volume change in the lungs; and </para>
          </listitem>
  <listitem>
            <para>2) the assumption that the process of oxygen binding to hemoglobin is at near equilibrium.</para>
          </listitem>
</itemizedlist>
<para>
Conditions under which these assumptions are valid have been studied, and the models are sufficiently flexible to be able to qualitatively explain a range of physiological observations.     
</para>

<para>
The models have been described here in CellML (the raw CellML descriptions of the four different Ben-Tal 2005 models can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>).     
</para>

<para>
The CellML files provided below represent the <emphasis>2 different versions of the aforementioned models A,B,C and D</emphasis>.
</para>

<para>
<informalfigure float="0" id="fig_reaction_diagram">
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    <imagedata fileref="ben-tal_2006a.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of inflexible lung model.</caption>
</informalfigure>
</para>

<para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="ben-tal_2006b.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of flexible lung model.</caption>
</informalfigure>
</para>

<para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="ben-tal_2006c.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of flexible lung model with gas exchange.</caption>
</informalfigure>
</para>

<para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="ben-tal_2006d.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of flexible lung model with gas exchange and gas transport.</caption>
</informalfigure>
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
Simplified models for gas exchange in the human lungs, Alona Ben-Tal, 2006. <ulink url="http://www.sciencedirect.com/science/journal/00225193">
	 <emphasis>Journal of Theoretical Biology</emphasis>
	 </ulink>, 238(2), 474-495.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=ID NUMBER&amp;dopt=Abstract">PubMed ID: 16038941</ulink>  </para>
	 
<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6WMD-4GNTX8S-3&amp;_user=140507&amp;_coverDate=01%2F21%2F2006&amp;_rdoc=1&amp;_fmt=&amp;_orig=search&amp;_sort=d&amp;view=c&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=7a4531dce8c0ef7379e5bedb4091c3a0">Full text (HTML)</ulink> and PDF versions of the article are available to subscribers on the Journal of Theoretical Biology website.
</para>

<informalfigure float="0" id="model_A_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
  </imageobject>
</mediaobject>
<caption>The lung modelled as a single, inflexible container.  Pm represents the mouth pressure, PA is the alveolar pressure, air flow is represented by q, R is the resistance to air flow and V0 is the volume of the container.</caption>
</informalfigure>

<informalfigure float="0" id="model_B_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
  </imageobject>
</mediaobject>
<caption>The lung modelled as a single, flexible container.  VA - total lung volume, Pm - mouth pressure, PL - pleural pressure, q - air flow, R - overall resistance of the conducting airways, ks - spring constant.</caption>
</informalfigure>

<informalfigure float="0" id="model_C_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
  </imageobject>
</mediaobject>
<caption>The lung modelled as a flexible container with gas exchange.  All the symbols are the same as in <xref linkend="model_B_diagram"/>.  In addition, fo and fc are the alveolar concentrations of oxygen and carbon dioxide respectively, and pao and pac are the alveolar partial pressures of oxygen and carbon dioxide respectively.  po and pc are the blood partial pressures of oxygen and carbon dioxide respectively.</caption>
</informalfigure>

<informalfigure float="0" id="model_D_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
  </imageobject>
</mediaobject>
<caption>The lung modelled as a flexible container with gas exchange and gas transport.  With each heart beat a new compartment is pushed into the lung.  Each compartment consists of a small container representing dissolved gas, and a large container representing the means by which oxygen and carbon dioxide are transported.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  
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