<?xml version="1.0" encoding="utf-8"?>
<model
name="autonomics_parent_model"
cmeta:id="autonomics_parent_model"
xmlns="http://www.cellml.org/cellml/1.1#"
xmlns:cellml="http://www.cellml.org/cellml/1.1#"
xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
xmlns:xlink="http://www.w3.org/1999/xlink">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomics_parent_model">
<rdf:value>
This is the CellML 1.1 "parent" file to test the Autonomics Model.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- ======================================== DOCUMENTATION ============================================= -->
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Guyton Model: Autonomics</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="cellml_1_1">
<title>CellML 1.1 Version</title>
<para>
This is a CellML 1.1 version of the Autonomics Module of the Guyton Circulation model. To run, click on "Solve using OpenCell" and all
dependent files and components will be imported. To run offline, please download all files from the <ulink url="/workspace/guyton_autonomics_2008/">workspace</ulink> into the same directory and open
"autonomics_parent.cellml" in OpenCell.
</para>
</section>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model has not been validated. The equations in this file may contain errors and the output from
the model may not conform to the results from the MODSIM program. Due to the differences between procedural
code (in this case C-code) and declarative languages (CellML), some aspects of the original model were not
able to be encapsulated by the CellML model (such as the damping of variables). Work is underway to fix these
omissions and validate the CellML model. We also anticipate that many of these problems will be fixed when the
CellML 1.0 models are combined in a CellML 1.1 format.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Arthur Guyton (1919-2003) was an American physiologist who became famous for his 1950s experiments in which he studied
the physiology of cardiac output and its relationship with the peripheral circulation. The results of these experiments
challenged the conventional wisdom that it was the heart itself that controlled cardiac output. Instead Guyton
demonstrated that it was the need of the body tissues for oxygen which was the real regulator of cardiac output.
The "Guyton Curves" describe the relationship between right atrial pressures and cardiac output, and they form a
foundation for understanding the physiology of circulation.
</para>
<para>
The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model of human
circulatory physiology, capable of simulating a variety of experimental conditions, and contains a number of linked
subsystems relating to circulation and its neuroendocrine control.
</para>
<para>
This is a CellML translation of the Guyton model of the regulation of the circulatory system. The complete model
consists of separate modules each of which characterise a separate physiological subsystems. The Circulation Dynamics
is the primary system, to which other modules/blocks are connected. The other modules characterise the dynamics of the
kidney, electrolytes and cell water, thirst and drinking, hormone regulation, autonomic regulation, cardiovascular
system etc, and these feedback on the central circulation model. The CellML code in these modules is based on the
C code from the programme C-MODSIM created by Dr Jean-Pierre Montani.
</para>
<para>
This particular CellML model describes the autonomic control of the circulation, which primarily operates through
the sympathetic system, though also to a slight extent through parasympathetic signals to the heart. These have been
lumped together, and there are basically three separate feedback mechanisms in this computational block.
These are: (1) feedback from the baroreceptor control system; (2) feedback from the peripheral chemoreceptors in
the carotid and aortic bodies,; and (3) feedback control of the circulatory system caused by central nervous system
ischemia, that is, ischemia of the vasomotor center of the brainstem. Several other inputs that affect the autonomic
nervous system are also included. These are: activation of the autonomic nervous system during exercise; baroreceptor
feedback effects from pulmonary artery pressure (PPA), left atrial pressure (PLA), and an effect of low blood PO2 (PO2ART).
</para>
<informalfigure float="0" id="full_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="full_model.png"/>
</imageobject>
</mediaobject>
<caption>A systems analysis diagram for the full Guyton model describing circulation regulation.</caption>
</informalfigure>
<informalfigure float="0" id="autonomics_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="autonomics.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the components and processes described in the current CellML model. Note: Not shown in
the diagram is also a variable (STA) that is normally zero. When it is set to any level above zero, the value of the
general autonomic multiplier (AU) becomes fixed to the value of STA.</caption>
</informalfigure>
<para>
There are several publications referring to the Guyton model. One of these papers is cited below:
</para>
<para>
Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972,
<emphasis>Annual Review of Physiology</emphasis>
, 34, 13-44. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4334846&query_hl=1&itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>
</sect1>
</article>
</documentation>
<!-- ======================================================= CITATION AND KEYWORD METADATA ================================================== -->
<rdf:RDF
xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
xmlns:bqs="http://www.cellml.org/bqs/1.0#"
xmlns:dc="http://purl.org/dc/elements/1.1/"
xmlns:dcterms="http://purl.org/dc/terms/"
xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<rdf:Description rdf:about="#autonomics_parent_model">
<bqs:reference rdf:parseType="Resource">
<bqs:JournalArticle rdf:parseType="Resource">
<dc:creator>
<rdf:Seq>
<rdf:li rdf:parseType="Resource">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
<vCard:N rdf:parseType="Resource">
<vCard:Family>Guyton</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
<vCard:N rdf:parseType="Resource">
<vCard:Family>Autonomics</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Description of Guyton autonomics module</dc:title>
<bqs:volume />
<bqs:first_page />
<bqs:last_page />
<bqs:Journal rdf:parseType="Resource">
<dc:title></dc:title>
</bqs:Journal>
<dcterms:issued rdf:parseType="Resource">
<dcterms:W3CDTF>2008-00-00 00:00</dcterms:W3CDTF>
</dcterms:issued>
</bqs:JournalArticle>
</bqs:reference>
<bqs:reference rdf:parseType="Resource">
<dc:subject rdf:parseType="Resource">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>
<rdf:Bag>
<rdf:li>physiology</rdf:li>
<rdf:li>organ systems</rdf:li>
<rdf:li>cardiovascular circulation</rdf:li>
<rdf:li>autonomics</rdf:li>
<rdf:li>Guyton</rdf:li>
</rdf:Bag>
</rdf:value>
</dc:subject>
</bqs:reference>
</rdf:Description>
</rdf:RDF>
<!-- ============================================= Import the required units from the Units file ==================================================== -->
<import xlink:href="units.cellml">
<units name="minute" units_ref="minute"/>
<units name="per_minute" units_ref="per_minute"/>
<units name="beats_per_minute" units_ref="beats_per_minute"/>
<units name="beats_per_minute_per_mmHg" units_ref="beats_per_minute_per_mmHg"/>
<units name="minute_per_L" units_ref="minute_per_L"/>
<units name="mmHg" units_ref="mmHg"/>
<units name="per_mmHg" units_ref="per_mmHg"/>
<units name="mmHg_per_mL" units_ref="mmHg_per_mL"/>
<units name="mmHg_L" units_ref="mmHg_L"/>
<units name="per_mmHg2" units_ref="per_mmHg2"/>
<units name="mmHg3" units_ref="mmHg3"/>
<units name="monovalent_mEq" units_ref="monovalent_mEq"/>
<units name="monovalent_mEq_per_minute" units_ref="monovalent_mEq_per_minute"/>
<units name="monovalent_mEq_per_litre" units_ref="monovalent_mEq_per_litre"/>
<units name="mOsm" units_ref="mOsm"/>
<units name="mOsm_per_litre" units_ref="mOsm_per_litre"/>
<units name="mOsm_per_minute" units_ref="mOsm_per_minute"/>
<units name="monovalent_mEq_per_litre_per_minute" units_ref="monovalent_mEq_per_litre_per_minute"/>
<units name="litre2_per_monovalent_mEq_per_minute" units_ref="litre2_per_monovalent_mEq_per_minute"/>
<units name="L_per_minute" units_ref="L_per_minute"/>
<units name="per_mmHg_per_minute" units_ref="per_mmHg_per_minute"/>
<units name="mL" units_ref="mL"/>
<units name="gram_per_L" units_ref="gram_per_L"/>
<units name="L_mmHg_per_gram" units_ref="L_mmHg_per_gram"/>
<units name="L2_mmHg_per_gram2" units_ref="L2_mmHg_per_gram2"/>
<units name="mmHg_minute_per_L" units_ref="mmHg_minute_per_L"/>
<units name="mmHg_L_per_minute" units_ref="mmHg_L_per_minute"/>
<units name="gram_per_minute" units_ref="gram_per_minute"/>
<units name="mL_per_L" units_ref="mL_per_L"/>
<units name="mL_per_L_per_mmHg" units_ref="mL_per_L_per_mmHg"/>
<units name="mL_per_L_per_minute" units_ref="mL_per_L_per_minute"/>
<units name="mL_per_minute_per_mmHg" units_ref="mL_per_minute_per_mmHg"/>
<units name="L_mL_per_minute_per_mmHg" units_ref="L_mL_per_minute_per_mmHg"/>
<units name="L_per_mL" units_ref="L_per_mL"/>
<units name="L_per_mmHg" units_ref="L_per_mmHg"/>
<units name="mL_per_minute" units_ref="mL_per_minute"/>
<units name="L_per_minute_per_mmHg" units_ref="L_per_minute_per_mmHg"/>
<units name="L_per_minute_per_mmHg2" units_ref="L_per_minute_per_mmHg2"/>
</import>
<!-- ===================================== Import all Parameters and State Variables from the Parameter file ============================================== -->
<import xlink:href="parameters.cellml">
<component component_ref="parameter_values" name="parameter_values"/>
<component component_ref="state_variables" name="state_variables"/>
</import>
<!-- ============================================ Import Environment Component from the Environment file ============================================== -->
<import xlink:href="environment.cellml">
<component component_ref="environment" name="environment"/>
</import>
<!-- ============================================ Import all the separate model files and their components ============================================== -->
<import xlink:href="autonomics.cellml">
<component component_ref="autonomics" name="autonomics"/>
</import>
<!-- ======================================== INPUT VALUES ============================================= -->
<component name="input_values"
cmeta:id="input_values">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#input_values">
<rdf:value>
Component to set all input values to 1.0 or a prescribed value.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<variable name="PA" initial_value="103.525" units="mmHg" private_interface="none" public_interface="out"/>
<variable name="PO2ART" initial_value="97.0439" units="mmHg" private_interface="none" public_interface="out"/>
<variable name="PLA" initial_value="2" units="mmHg" private_interface="none" public_interface="out"/>
<variable name="PRA" initial_value="0.00852183" units="mmHg" private_interface="none" public_interface="out"/>
<variable name="PPA" initial_value="15.6376" units="mmHg" private_interface="none" public_interface="out"/>
</component>
<!-- AUTONOMICS INPUT CONNECTIONS -->
<connection>
<map_components component_1="autonomics" component_2="input_values"/>
<map_variables variable_1="PA" variable_2="PA"/>
<map_variables variable_1="PO2ART" variable_2="PO2ART"/>
<map_variables variable_1="PLA" variable_2="PLA"/>
<map_variables variable_1="PRA" variable_2="PRA"/>
<map_variables variable_1="PPA" variable_2="PPA"/>
</connection>
<connection>
<map_components component_1="autonomics" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
</model>
