<?xml version="1.0" encoding="utf-8"?>
<model
name="autonomics_CellML1_0_model"
cmeta:id="autonomics_CellML1_0_model"
xmlns="http://www.cellml.org/cellml/1.0#"
xmlns:cellml="http://www.cellml.org/cellml/1.0#"
xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
xmlns:xlink="http://www.w3.org/1999/xlink">
<!-- ======================================== 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="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_CellML1_0_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>
<!-- ======================================================= UNITS ================================================== -->
<units name="minute">
<unit multiplier="60" units="second"/>
</units>
<units name="per_minute">
<unit units="minute" exponent="-1"/>
</units>
<units name="mmHg">
<unit multiplier="133.322" units="newton"/>
<unit units="metre" exponent="-2"/>
</units>
<units name="per_mmHg">
<unit units="mmHg" exponent="-1"/>
</units>
<units name="mmHg_per_mL">
<unit units="mmHg"/>
<unit units="mL" exponent="-1"/>
</units>
<units name="mmHg_L">
<unit units="mmHg"/>
<unit units="litre"/>
</units>
<units name="per_mmHg2">
<unit units="mmHg" exponent="-2"/>
</units>
<units name="mmHg3">
<unit units="mmHg" exponent="3"/>
</units>
<units name="monovalent_mEq">
<unit units="mole" prefix="milli"/>
</units>
<units name="monovalent_mEq_per_minute">
<unit units="mole" prefix="milli"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="monovalent_mEq_per_litre">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="monovalent_mEq_per_litre_per_minute">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="litre2_per_monovalent_mEq_per_minute">
<unit units="litre" exponent="2"/>
<unit units="mole" prefix="milli" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="L_per_minute">
<unit units="litre"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="mL">
<unit units="litre" prefix="milli"/>
</units>
<units name="gram_per_L">
<unit units="gram"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="L_mmHg_per_gram">
<unit units="litre"/>
<unit units="mmHg"/>
<unit units="gram" exponent="-1"/>
</units>
<units name="L2_mmHg_per_gram2">
<unit units="litre" exponent="2"/>
<unit units="mmHg"/>
<unit units="gram" exponent="-2"/>
</units>
<units name="mmHg_minute_per_L">
<unit units="minute"/>
<unit units="mmHg"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="gram_per_minute">
<unit units="gram"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="mL_per_L">
<unit units="litre" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="mL_per_L_per_mmHg">
<unit units="litre" prefix="milli"/>
<unit units="litre" exponent="-1"/>
<unit units="mmHg" exponent="-1"/>
</units>
<units name="mL_per_L_per_minute">
<unit units="litre" prefix="milli"/>
<unit units="litre" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="mL_per_minute_per_mmHg">
<unit units="litre" prefix="milli"/>
<unit units="minute" exponent="-1"/>
<unit units="mmHg" exponent="-1"/>
</units>
<units name="L_mL_per_minute_per_mmHg">
<unit units="litre"/>
<unit units="litre" prefix="milli"/>
<unit units="minute" exponent="-1"/>
<unit units="mmHg" exponent="-1"/>
</units>
<units name="L_per_mL">
<unit units="litre" prefix="milli" exponent="-1"/>
<unit units="litre"/>
</units>
<units name="mL_per_minute">
<unit units="mL"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="L_per_minute_per_mmHg">
<unit units="litre"/>
<unit units="minute" exponent="-1"/>
<unit units="mmHg" exponent="-1"/>
</units>
<!-- ========================================================================================================================== -->
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomics_CellML1_0_model">
<rdf:value>
Autonomic Control Of The Circulation
Autonomic control of the circulation primarily operates through the sympathetic
system, though 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).
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.
WHERE DO I PUT THIS NOTE?????
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- ======================================== ENVIRONMENT COMPONENT ============================================= -->
<component name="environment">
<variable cmeta:id="environment_time"
name="time" units="minute" private_interface="none" public_interface="out"/>
</component>
<!-- ======================================== AUTONOMICS TOP-LEVEL COMPONENT ============================================= -->
<component name="autonomics"
cmeta:id="autonomics">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomics">
<rdf:value>
Encapsulation grouping component containing all the components in the Autonomics Model. The inputs and
outputs of the Autonomics Model must be passed by this component.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<variable name="time" units="minute" private_interface="out" public_interface="in"/>
<!-- Inputs from components in other models -->
<variable name="PA" initial_value="103.525" units="mmHg" private_interface="out" public_interface="none"/>
<variable name="PO2ART" initial_value="97.0439" units="mmHg" private_interface="out" public_interface="none"/>
<variable name="PLA" initial_value="2" units="mmHg" private_interface="out" public_interface="none"/>
<variable name="PRA" initial_value="0.00852183" units="mmHg" private_interface="out" public_interface="none"/>
<variable name="PPA" initial_value="15.6376" units="mmHg" private_interface="out" public_interface="none"/>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="autonomics" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== PRESSURE DRIVING AUTONOMIC RECEPTORS, PA1 ============================================= -->
<component name="pressure_driving_autonomic_receptors"
cmeta:id="pressure_driving_autonomic_receptors">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#pressure_driving_autonomic_receptors">
<rdf:value>
AU1:
Calculation of the effective systemic arterial pressure (PA1) by subtracting
any pressure drop (EXE) between the output point of the heart where the pressure
is equal to PA and the remainder of the aortic tree where the pressure will be
equal to PA1. This block allows simulation of aortic constriction at its root.
AU2:
A block that will allow one to set the effective systemic arterial pressure (PA1)
to any constant value desired by increasing the value CRRFLX to any value above zero.
As long as it remains at zero, there is no effect.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU1_and_AU2">
<rdf:value>
AU1:
Calculation of the effective systemic arterial pressure (PA1) by subtracting
any pressure drop (EXE) between the output point of the heart where the pressure
is equal to PA and the remainder of the aortic tree where the pressure will be
equal to PA1. This block allows simulation of aortic constriction at its root.
AU2:
A block that will allow one to set the effective systemic arterial pressure (PA1)
to any constant value desired by increasing the value CRRFLX to any value above zero.
As long as it remains at zero, there is no effect.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PA" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="pressure_driving_autonomic_receptors_PA1"
name="PA1" units="mmHg" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="CRRFLX" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="EXE" units="mmHg" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU1_and_AU2">
<eq/>
<ci>PA1</ci>
<piecewise>
<piece>
<ci>CRRFLX</ci>
<apply>
<gt/>
<ci>CRRFLX</ci>
<cn cellml:units="mmHg">0.0000001</cn>
</apply>
</piece>
<otherwise>
<apply>
<minus/>
<ci>PA</ci>
<ci>EXE</ci>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="pressure_driving_autonomic_receptors" component_2="autonomics"/>
<map_variables variable_1="PA" variable_2="PA"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="pressure_driving_autonomic_receptors" component_2="parameter_values"/>
<map_variables variable_1="CRRFLX" variable_2="CRRFLX"/>
<map_variables variable_1="EXE" variable_2="EXE"/>
</connection>
<!-- ======================================== CHEMORECEPTORS - EFFECT OF PA ============================================= -->
<component name="chemoreceptors_effect_of_PA"
cmeta:id="chemoreceptors_effect_of_PA">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#chemoreceptors_effect_of_PA">
<rdf:value>
AU4:
Calculation of the nervous output from the chemoreceptors (AUC) at the
different systemic arterial pressure levels (PA1).
AU19:
Sensitivity control for increasing or decreasing the degree of response of
AUC to chemoreceptor nervous output.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU4_and_AU19">
<rdf:value>
AU4:
Calculation of the nervous output from the chemoreceptors (AUC) at the
different systemic arterial pressure levels (PA1).
AU19:
Sensitivity control for increasing or decreasing the degree of response of
AUC to chemoreceptor nervous output.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PA1" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AUC" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AUC1" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU4_and_AU19">
<eq/>
<ci>AUC</ci>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="per_mmHg">0.005</cn>
<apply>
<minus/>
<cn cellml:units="mmHg">80</cn>
<ci>PA1</ci>
</apply>
<ci>AUC1</ci>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>PA1</ci>
<cn cellml:units="mmHg">80</cn>
</apply>
<apply>
<geq/>
<ci>PA1</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
</apply>
</piece>
<piece>
<apply>
<times/>
<cn cellml:units="dimensionless">0.2</cn>
<ci>AUC1</ci>
</apply>
<apply>
<lt/>
<ci>PA1</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="chemoreceptors_effect_of_PA" component_2="pressure_driving_autonomic_receptors"/>
<map_variables variable_1="PA1" variable_2="PA1"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="chemoreceptors_effect_of_PA" component_2="parameter_values"/>
<map_variables variable_1="AUC1" variable_2="AUC1"/>
</connection>
<!-- ======================================== CHEMORECEPTORS - EFFECT OF ARTERIAL PO2 ============================================= -->
<component name="chemoreceptors_effect_of_art_PO2"
cmeta:id="chemoreceptors_effect_of_art_PO2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#chemoreceptors_effect_of_art_PO2">
<rdf:value>
AU20:
Calculation of a nervous factor (AUC2) for effecting autonomic control of
the circulation depending on the peripheral level of oxygen in the blood (PO2ART).
O2CHMO is a sensitivity controller.
AU21:
Addition of the chemoreflex output (AUC) caused by activation of the chemoreceptors
by low arterial pressure plus the chemoreceptor output (AUC2) caused by reduced
arterial oxygen saturation (PO2ART). The output of Block 21 is equal to AUC3.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU20">
<rdf:value>
AU20:
Calculation of a nervous factor (AUC2) for effecting autonomic control of
the circulation depending on the peripheral level of oxygen in the blood (PO2ART).
O2CHMO is a sensitivity controller.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU21">
<rdf:value>
AU21:
Addition of the chemoreflex output (AUC) caused by activation of the chemoreceptors
by low arterial pressure plus the chemoreceptor output (AUC2) caused by reduced
arterial oxygen saturation (PO2ART). The output of Block 21 is equal to AUC3.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PO2ART" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="AUC" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AUC3" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="O2CHMO" units="per_mmHg" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AUC2" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU20">
<eq/>
<ci>AUC2</ci>
<piecewise>
<piece>
<apply>
<times/>
<ci>O2CHMO</ci>
<apply>
<minus/>
<cn cellml:units="mmHg">80</cn>
<ci>PO2ART</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>PO2ART</ci>
<cn cellml:units="mmHg">80</cn>
</apply>
<apply>
<geq/>
<ci>PO2ART</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
</apply>
</piece>
<piece>
<apply>
<times/>
<ci>O2CHMO</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
<apply>
<lt/>
<ci>PO2ART</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
<apply id="AU21">
<eq/>
<ci>AUC3</ci>
<apply>
<plus/>
<ci>AUC</ci>
<ci>AUC2</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="chemoreceptors_effect_of_art_PO2" component_2="autonomics"/>
<map_variables variable_1="PO2ART" variable_2="PO2ART"/>
</connection>
<connection>
<map_components component_1="chemoreceptors_effect_of_art_PO2" component_2="chemoreceptors_effect_of_PA"/>
<map_variables variable_1="AUC" variable_2="AUC"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="chemoreceptors_effect_of_art_PO2" component_2="parameter_values"/>
<map_variables variable_1="O2CHMO" variable_2="O2CHMO"/>
</connection>
<!-- ======================================== BARO REFLEX / ARTERIAL BARORECEPTORS ============================================= -->
<!-- ======================================== FIX!!!! - MISSING AU17 and AU14-16!!! ============================================= -->
<component name="arterial_baroreceptor_reflex"
cmeta:id="arterial_baroreceptor_reflex">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#arterial_baroreceptor_reflex">
<rdf:value>
AU3:
Calculation of the nervous output from the baroreceptors (AUB) at the different
systemic arterial pressure levels (PA1).
AU6, AU7, and AU8:
Sensitivity control of the effect of baroreceptor reflex output (AUB) on the
autonomic nervous system. The output of this sensitivity controller is AU6A,
and the degree of sensitivity control is equal to AUX.
AU9, AU10, and AU11:
Time delay in the buildup of sympathetic output (AU6) that results from changes
in baroreceptor reflex nervous output (AU6A). The time constant of this delay
circuit is equal to BAROTC.
AU14, AU15, and AU16:
Calculation of adaptation of the baroreceptor feedback mechanism (AU4) over a
period of hours. The time constant of this adaptation is equal to AUK.
THIS IS COMMENTED OUT BECAUSE IT IS NOT IN THE MODSIM CODE
AU17:
This block sets AU6 equal to AU6A irrespective of the time constant for buildup
of the nervous effect of the baroreceptor reflex when the iteration interval for
solution of the equations is greater than .16666. This prevents some instability
when the equations are being calculated for long-term instead of short-term changes.
AU18:
Damping of baroreceptor autonomic feedback output (AU6) when long-term solutions are
being calculated, to prevent oscillation in the circuit. The output after the damping
is AU6C. MDMP sets the degree of damping.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU3">
<rdf:value>
AU3:
Calculation of the nervous output from the baroreceptors (AUB) at the different
systemic arterial pressure levels (PA1).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU6_AU7_and_part_AU8">
<rdf:value>
AU6, AU7, and AU8:
Sensitivity control of the effect of baroreceptor reflex output (AUB) on the
autonomic nervous system. The output of this sensitivity controller is AU6A,
and the degree of sensitivity control is equal to AUX.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#rest_AU8">
<rdf:value>
AU6, AU7, and AU8:
Sensitivity control of the effect of baroreceptor reflex output (AUB) on the
autonomic nervous system. The output of this sensitivity controller is AU6A,
and the degree of sensitivity control is equal to AUX.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU9_to_AU11">
<rdf:value>
AU9, AU10, and AU11:
Time delay in the buildup of sympathetic output (AU6) that results from changes
in baroreceptor reflex nervous output (AU6A). The time constant of this delay
circuit is equal to BAROTC.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU14_to_AU16">
<rdf:value>
AU14, AU15, and AU16:
Calculation of adaptation of the baroreceptor feedback mechanism (AU4) over a
period of hours. The time constant of this adaptation is equal to AUK.
THIS IS COMMENTED OUT BECAUSE IT IS NOT IN THE MODSIM CODE
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU18">
<rdf:value>
AU18:
Damping of baroreceptor autonomic feedback output (AU6) when long-term solutions are
being calculated, to prevent oscillation in the circuit. The output after the damping
is AU6C. MDMP sets the degree of damping.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PA1" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AU6C" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AUX" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUK" units="per_minute" private_interface="none" public_interface="in"/>
<variable name="BAROTC" units="minute" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AUB" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="A1B" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AU6A" units="dimensionless" private_interface="none" public_interface="none"/>
<!-- <variable name="AU8" units="per_minute" private_interface="none" public_interface="none"/>
<variable name="AU2" units="dimensionless" private_interface="none" public_interface="none"/> -->
<variable name="AU4" initial_value="-0.060024" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AU6" initial_value="1.00132" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU3">
<eq/>
<ci>AUB</ci>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="per_mmHg">0.016667</cn>
<apply>
<minus/>
<cn cellml:units="mmHg">160</cn>
<ci>PA1</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>PA1</ci>
<cn cellml:units="mmHg">160</cn>
</apply>
<apply>
<geq/>
<ci>PA1</ci>
<cn cellml:units="mmHg">80</cn>
</apply>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1.3336</cn>
<apply>
<lt/>
<ci>PA1</ci>
<cn cellml:units="mmHg">80</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
<apply id="AU6_AU7_and_part_AU8">
<eq/>
<ci>A1B</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>AUB</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AUX</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="rest_AU8">
<eq/>
<ci>AU6A</ci>
<apply>
<minus/>
<ci>A1B</ci>
<ci>AU4</ci>
</apply>
</apply>
<apply id="AU9_to_AU11">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AU6</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>AU6A</ci>
<ci>AU6</ci>
</apply>
<ci>BAROTC</ci>
</apply>
</apply>
<!-- <apply id="AU14">
<eq/>
<ci>AU2</ci>
<apply>
<minus/>
<ci>AU6</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU15">
<eq/>
<ci>AU8</ci>
<apply>
<times/>
<ci>AUK</ci>
<ci>AU2</ci>
</apply>
</apply>
<apply id="AU16">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AU4</ci>
</apply>
<ci>AU8</ci>
</apply> -->
<apply id="AU18">
<eq/>
<ci>AU6C</ci>
<ci>AU6</ci>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="arterial_baroreceptor_reflex" component_2="pressure_driving_autonomic_receptors"/>
<map_variables variable_1="PA1" variable_2="PA1"/>
</connection>
<connection>
<map_components component_1="arterial_baroreceptor_reflex" component_2="autonomics"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="arterial_baroreceptor_reflex" component_2="parameter_values"/>
<map_variables variable_1="AUX" variable_2="AUX"/>
<map_variables variable_1="AUK" variable_2="AUK"/>
<map_variables variable_1="BAROTC" variable_2="BAROTC"/>
</connection>
<!-- ======================================== CNS ISCHEMIC REFLEX ============================================= -->
<component name="CNS_ischemic_reflex"
cmeta:id="CNS_ischemic_reflex">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#CNS_ischemic_reflex">
<rdf:value>
AU5:
Calculation of the nervous output (AUN) caused by activation of the central
nervous system ischemic reflex, resulting from reduced systemic arterial
pressure (PA1).
AU22:
Control of the sensitivity of the CNS ischemic reflex output by the sensitivity
controller AUN1.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU5_and_AU22">
<rdf:value>
AU5:
Calculation of the nervous output (AUN) caused by activation of the central
nervous system ischemic reflex, resulting from reduced systemic arterial
pressure (PA1).
AU22:
Control of the sensitivity of the CNS ischemic reflex output by the sensitivity
controller AUN1.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PA1" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AUN" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AUN1" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU5_and_AU22">
<eq/>
<ci>AUN</ci>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="per_mmHg">0.04</cn>
<apply>
<minus/>
<cn cellml:units="mmHg">40</cn>
<ci>PA1</ci>
</apply>
<ci>AUN1</ci>
</apply>
<apply>
<lt/>
<ci>PA1</ci>
<cn cellml:units="mmHg">40</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="CNS_ischemic_reflex" component_2="pressure_driving_autonomic_receptors"/>
<map_variables variable_1="PA1" variable_2="PA1"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="CNS_ischemic_reflex" component_2="parameter_values"/>
<map_variables variable_1="AUN1" variable_2="AUN1"/>
</connection>
<!-- ============================== STRETCH RECEPTORS - RESPONSE TO PRESSURE IN PULMONARY VASCULATURE ==================================== -->
<component name="autonomic_response_to_vasculature_pressure"
cmeta:id="autonomic_response_to_vasculature_pressure">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomic_response_to_vasculature_pressure">
<rdf:value>
AU24, AU25, AU26, AU27, and AU28:
Calculation of an additional factor (AULP) that affects the total autonomic
response, caused by stretch receptors in the pulmonary vasculature. These
are in response to left atrial pressure (PLA), right atrial pressure (PRA),
and pulmonary arterial pressure (PPA). The sensitivity controller for these
effects is AULPM in Block 27.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU24_to_AU28">
<rdf:value>
AU24, AU25, AU26, AU27, and AU28:
Calculation of an additional factor (AULP) that affects the total autonomic
response, caused by stretch receptors in the pulmonary vasculature. These
are in response to left atrial pressure (PLA), right atrial pressure (PRA),
and pulmonary arterial pressure (PPA). The sensitivity controller for these
effects is AULPM in Block 27.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PLA" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="PRA" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="PPA" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AULP" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AULPM" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU24_to_AU28">
<eq/>
<ci>AULP</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<divide/>
<cn cellml:units="mmHg">15</cn>
<apply>
<plus/>
<ci>PLA</ci>
<ci>PRA</ci>
<ci>PPA</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AULPM</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="autonomic_response_to_vasculature_pressure" component_2="autonomics"/>
<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>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="autonomic_response_to_vasculature_pressure" component_2="parameter_values"/>
<map_variables variable_1="AULPM" variable_2="AULPM"/>
</connection>
<!-- ======================================== EFFECT OF EXERCISE ON AUTONOMIC OUTPUT ============================================= -->
<component name="autonomic_response_to_exercise"
cmeta:id="autonomic_response_to_exercise">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomic_response_to_exercise">
<rdf:value>
AU29, AU30, AU31, and AU32:
Effect of the exercise nervous signal (EXC) on autonomic output. The
exponent (EXCXP) in Block 29 provides a curve fitting effect of exercise on the
autonomic output, and the factor (EXCML) is a sensitivity multiplier effect.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU29_to_AU32">
<rdf:value>
AU29, AU30, AU31, and AU32:
Effect of the exercise nervous signal (EXC) on autonomic output. The
exponent (EXCXP) in Block 29 provides a curve fitting effect of exercise on the
autonomic output, and the factor (EXCML) is a sensitivity multiplier effect.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Outputs to other components -->
<variable name="AUEX" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="EXC" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="EXCXP" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU29_to_AU32">
<eq/>
<ci>AUEX</ci>
<apply>
<power/>
<ci>EXC</ci>
<ci>EXCXP</ci>
</apply>
</apply>
</math>
</component>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="autonomic_response_to_exercise" component_2="parameter_values"/>
<map_variables variable_1="EXC" variable_2="EXC"/>
<map_variables variable_1="EXCXP" variable_2="EXCXP"/>
</connection>
<!-- ======================================== TOTAL AUTONOMIC STIMULATION ============================================= -->
<component name="total_autonomic_stimulation"
cmeta:id="total_autonomic_stimulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#total_autonomic_stimulation">
<rdf:value>
AU23:
Summation of the different nervous output controls of autonomic stimulation, AUC3
from the chemoreceptor component, AU6C from the arterial baroreceptor reflex component,
and the output of Block 22 from the CNS ischemic reflex component.
AU33:
Summation of all of the different factors affecting autonomic stimulation
of the circulation, giving a total output of AUTTL.
AU34:
Limitation of the lower level of autonomic stimulation of the circulatory system
so that this cannot fall below the level of zero.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU23_and_AU33">
<rdf:value>
AU23:
Summation of the different nervous output controls of autonomic stimulation, AUC3
from the chemoreceptor component, AU6C from the arterial baroreceptor reflex component,
and the output of Block 22 from the CNS ischemic reflex component.
AU33:
Summation of all of the different factors affecting autonomic stimulation
of the circulation, giving a total output of AUTTL.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU34">
<rdf:value>
AU34:
Limitation of the lower level of autonomic stimulation of the circulatory system
so that this cannot fall below the level of zero.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AUC3" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AU6C" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUN" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AULP" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUEX" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="AUTTL" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Internal variables -->
<variable name="AUTTL1" units="dimensionless" private_interface="none" public_interface="none"/>
<!-- Parameters from parameter_file -->
<variable name="EXCML" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU23_and_AU33">
<eq/>
<ci>AUTTL1</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<times/>
<ci>AUEX</ci>
<ci>AULP</ci>
<apply>
<plus/>
<ci>AUC3</ci>
<ci>AU6C</ci>
<ci>AUN</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>EXCML</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU34">
<eq/>
<ci>AUTTL</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>AUTTL1</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<ci>AUTTL1</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="chemoreceptors_effect_of_art_PO2"/>
<map_variables variable_1="AUC3" variable_2="AUC3"/>
</connection>
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="arterial_baroreceptor_reflex"/>
<map_variables variable_1="AU6C" variable_2="AU6C"/>
</connection>
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="CNS_ischemic_reflex"/>
<map_variables variable_1="AUN" variable_2="AUN"/>
</connection>
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="autonomic_response_to_vasculature_pressure"/>
<map_variables variable_1="AULP" variable_2="AULP"/>
</connection>
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="autonomic_response_to_exercise"/>
<map_variables variable_1="AUEX" variable_2="AUEX"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="total_autonomic_stimulation" component_2="parameter_values"/>
<map_variables variable_1="EXCML" variable_2="EXCML"/>
</connection>
<!-- ======================================== ACTUAL AUTONOMIC STIMULATION ============================================= -->
<component name="actual_autonomic_stimulation"
cmeta:id="actual_autonomic_stimulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#actual_autonomic_stimulation">
<rdf:value>
AU35, AU36, and AU37:
This is a time-delay circuit to delay the peripheral changes that occur in the
circulatory system for a fraction of a minute after changes in the nervous component
take place. This results from the need to build up autonomic transmitter substance
and for the different organs to respond. The output after this delay circuit is AU1.
The time constant of the delay is AUDMP.
AU38:
This is a curve fitting step to fit the output strength of functional reaction to
sympathetic stimulation (AU) to the input level of nervous stimulation (AU1).
The maximum level of AU is set by the equation in this block to equal AUMAX.
AUSLPC determines the slope of the relationship.
AU39:
This sets the minimum level of AU (the output functional reaction) equal to a
minimum value of AUMIN.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU35">
<rdf:value>
AU35, AU36, and AU37:
This is a time-delay circuit to delay the peripheral changes that occur in the
circulatory system for a fraction of a minute after changes in the nervous component
take place. This results from the need to build up autonomic transmitter substance
and for the different organs to respond. The output after this delay circuit is AU1.
The time constant of the delay is AUDMP.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU36_and_AU37">
<rdf:value>
AU35, AU36, and AU37:
This is a time-delay circuit to delay the peripheral changes that occur in the
circulatory system for a fraction of a minute after changes in the nervous component
take place. This results from the need to build up autonomic transmitter substance
and for the different organs to respond. The output after this delay circuit is AU1.
The time constant of the delay is AUDMP.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU38">
<rdf:value>
AU38:
This is a curve fitting step to fit the output strength of functional reaction to
sympathetic stimulation (AU) to the input level of nervous stimulation (AU1).
The maximum level of AU is set by the equation in this block to equal AUMAX.
AUSLPC determines the slope of the relationship.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU39">
<rdf:value>
AU39:
This sets the minimum level of AU (the output functional reaction) equal to a
minimum value of AUMIN.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AUTTL" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="actual_autonomic_stimulation_AU"
name="AU" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="AUDMP" units="minute" private_interface="none" public_interface="in"/>
<variable name="AUMAX" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUMIN" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUSLP" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="DAU" units="per_minute" private_interface="none" public_interface="none"/>
<variable name="AU1" initial_value="1.00007" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="AUT" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU35">
<eq/>
<ci>DAU</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>AUTTL</ci>
<ci>AU1</ci>
</apply>
<ci>AUDMP</ci>
</apply>
</apply>
<apply id="AU36_and_AU37">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AU1</ci>
</apply>
<ci>DAU</ci>
</apply>
<apply id="AU38">
<eq/>
<ci>AUT</ci>
<apply>
<minus/>
<ci>AUMAX</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>AUMAX</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<exp/>
<apply>
<times/>
<ci>AUSLP</ci>
<apply>
<minus/>
<ci>AU1</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="AU39">
<eq/>
<ci>AU</ci>
<piecewise>
<piece>
<ci>AUMIN</ci>
<apply>
<lt/>
<ci>AUT</ci>
<ci>AUMIN</ci>
</apply>
</piece>
<otherwise>
<ci>AUT</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="actual_autonomic_stimulation" component_2="total_autonomic_stimulation"/>
<map_variables variable_1="AUTTL" variable_2="AUTTL"/>
</connection>
<connection>
<map_components component_1="actual_autonomic_stimulation" component_2="autonomics"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="actual_autonomic_stimulation" component_2="parameter_values"/>
<map_variables variable_1="AUDMP" variable_2="AUDMP"/>
<map_variables variable_1="AUMAX" variable_2="AUMAX"/>
<map_variables variable_1="AUMIN" variable_2="AUMIN"/>
<map_variables variable_1="AUSLP" variable_2="AUSLP"/>
</connection>
<!-- ============================== AUTONOMIC DRIVE ON THE VARIOUS TARGET ORGANS AND TISSUES ================================= -->
<!-- ============================== FIX!!! - AU47 AND AU48 NOT IN ORIGINAL CODE BUT ARE ON DIAGRAM!!!! ================================= -->
<component name="autonomic_drive_on_target_organs_and_tissues"
cmeta:id="autonomic_drive_on_target_organs_and_tissues">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#autonomic_drive_on_target_organs_and_tissues">
<rdf:value>
AU40 and AU41:
Calculation of the effect on venous vascular resistance (VVR) of different
levels of autonomic functional reaction (AU). The sensitivity control is AUL,
and VV9 determines the range.
AU42:
A step to reduce the output effect of normal autonomic reaction (AU) equal to
zero (AUO) so that differences from control levels can be activated in
Blocks 43, 45, 47, 50, and 53.
AU43 and AU44:
Sensitivity control for the autonomic effect on the heart (AUH). The sensitivity
is controlled by AUV.
AU45 and AU46:
Sensitivity control of the autonomic effect on heart rate (AUR). The sensitivity
is controlled by AUS.
AU47 and AU48:
Calculation of the autonomic effect on muscle metabolism (AOM). The sensitivity
control for this variable is O2A.
AU50, AU51, and AU52:
Calculation of an autonomic multiplier effect that is used at multiple points in
the circulatory system (AUM). The values AUM1 and AUM2 are curve fitting controls.
AU53 and AU54:
Sensitivity control for adjusting the autonomic multiplier effect on the
venous tree (AVE). The variable (AUY) controls the sensitivity.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU40_and_AU41">
<rdf:value>
AU40 and AU41:
Calculation of the effect on venous vascular resistance (VVR) of different
levels of autonomic functional reaction (AU). The sensitivity control is AUL,
and VV9 determines the range.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU42">
<rdf:value>
AU42:
A step to reduce the output effect of normal autonomic reaction (AU) equal to
zero (AUO) so that differences from control levels can be activated in
Blocks 43, 45, 47, 50, and 53.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU43_and_AU44">
<rdf:value>
AU43 and AU44:
Sensitivity control for the autonomic effect on the heart (AUH). The sensitivity
is controlled by AUV.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU45_and_AU46">
<rdf:value>
AU45 and AU46:
Sensitivity control of the autonomic effect on heart rate (AUR). The sensitivity
is controlled by AUS.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU47_and_AU48">
<rdf:value>
AU47 and AU48:
Calculation of the autonomic effect on muscle metabolism (AOM). The sensitivity
control for this variable is O2A.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU50_to_AU52">
<rdf:value>
AU50, AU51, and AU52:
Calculation of an autonomic multiplier effect that is used at multiple points in
the circulatory system (AUM). The values AUM1 and AUM2 are curve fitting controls.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#AU53_and_AU54">
<rdf:value>
AU53 and AU54:
Sensitivity control for adjusting the autonomic multiplier effect on the
venous tree (AVE). The variable (AUY) controls the sensitivity.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AU" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_VVR"
name="VVR" units="litre" private_interface="none" public_interface="out"/>
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_AUH"
name="AUH" units="dimensionless" private_interface="none" public_interface="out"/>
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_AUR"
name="AUR" units="dimensionless" private_interface="none" public_interface="out"/>
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_AOM"
name="AOM" units="dimensionless" private_interface="none" public_interface="out"/>
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_AUM"
name="AUM" units="dimensionless" private_interface="none" public_interface="out"/>
<variable cmeta:id="autonomic_drive_on_target_organs_and_tissues_AVE"
name="AVE" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="VV9" units="litre" private_interface="none" public_interface="in"/>
<variable name="AUL" units="litre" private_interface="none" public_interface="in"/>
<variable name="AUV" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUS" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="O2A" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUM1" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUM2" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AUY" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="AUO" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="AU40_and_AU41">
<eq/>
<ci>VVR</ci>
<apply>
<plus/>
<apply>
<minus/>
<ci>VV9</ci>
<apply>
<times/>
<ci>AU</ci>
<ci>AUL</ci>
</apply>
</apply>
<ci>AUL</ci>
</apply>
</apply>
<apply id="AU42">
<eq/>
<ci>AUO</ci>
<apply>
<minus/>
<ci>AU</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU43_and_AU44">
<eq/>
<ci>AUH</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>AUO</ci>
<ci>AUV</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU45_and_AU46">
<eq/>
<ci>AUR</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>AUO</ci>
<ci>AUS</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU47_and_AU48">
<eq/>
<ci>AOM</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>AUO</ci>
<ci>O2A</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply id="AU50_to_AU52">
<eq/>
<ci>AUM</ci>
<apply>
<power/>
<apply>
<plus/>
<apply>
<times/>
<ci>AUO</ci>
<ci>AUM1</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>AUM2</ci>
</apply>
</apply>
<apply id="AU53_and_AU54">
<eq/>
<ci>AVE</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>AUO</ci>
<ci>AUY</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="autonomic_drive_on_target_organs_and_tissues" component_2="actual_autonomic_stimulation"/>
<map_variables variable_1="AU" variable_2="AU"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="autonomic_drive_on_target_organs_and_tissues" component_2="parameter_values"/>
<map_variables variable_1="VV9" variable_2="VV9"/>
<map_variables variable_1="AUL" variable_2="AUL"/>
<map_variables variable_1="AUV" variable_2="AUV"/>
<map_variables variable_1="AUS" variable_2="AUS"/>
<map_variables variable_1="O2A" variable_2="O2A"/>
<map_variables variable_1="AUM1" variable_2="AUM1"/>
<map_variables variable_1="AUM2" variable_2="AUM2"/>
<map_variables variable_1="AUY" variable_2="AUY"/>
</connection>
<!-- ============================================================== PARAMETER VALUES ========================================================== -->
<component name="parameter_values"
cmeta:id="parameter_values">
<variable name="VV9" units="litre" initial_value="2.51" private_interface="none" public_interface="out"/> <!-- basic venous volume, without autonomic drive [P] -->
<variable name="AUL" units="litre" initial_value="1.5" private_interface="none" public_interface="out"/> <!-- curve fitting coefficient, calculation VVR [P] -->
<variable name="AULPM" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AULP [P] -->
<variable name="AUY" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- sensitivity of sympathetic control of veins -->
<variable name="AUV" units="dimensionless" initial_value="0.55" private_interface="none" public_interface="out"/> <!-- blood volume shifted from unstressed to stressed -->
<variable name="AUS" units="dimensionless" initial_value="1" private_interface="none" public_interface="out"/> <!-- sensitivity of sympathetic control of heart rate [P] -->
<variable name="O2A" units="dimensionless" initial_value="0.1" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AOM, autonomic on metabolism [P] -->
<variable name="AUM1" units="dimensionless" initial_value="3" private_interface="none" public_interface="out"/> <!-- curve fitting coefficient, calculation AUM [P] -->
<variable name="AUM2" units="dimensionless" initial_value="1" private_interface="none" public_interface="out"/> <!-- curve fitting exponent, calculation AUM [P] -->
<variable name="AUDMP" units="minute" initial_value="0.3" private_interface="none" public_interface="out"/> <!-- damping factor for AU1 [P] -->
<variable name="AUMAX" units="dimensionless" initial_value="5.0" private_interface="none" public_interface="out"/> <!-- maximal autonomic output [P] -->
<variable name="AUMIN" units="dimensionless" initial_value="0.4" private_interface="none" public_interface="out"/> <!-- minimal autonomic output [P] -->
<variable name="AUSLP" units="dimensionless" initial_value="1.5" private_interface="none" public_interface="out"/> <!-- curve fitting coefficient, calculation AU [P] -->
<variable name="EXC" units="dimensionless" initial_value="1" private_interface="none" public_interface="out"/> <!-- level of exercise activity [P] -->
<variable name="EXCML" units="dimensionless" initial_value="0.01" private_interface="none" public_interface="out"/> <!-- sensitivity controller of exercise on autonomics [P] -->
<variable name="EXCXP" units="dimensionless" initial_value="1.0" private_interface="none" public_interface="out"/> <!-- curve fitting exponent, autonomic effect of exercise [P] -->
<variable name="AUN1" units="dimensionless" initial_value="0.5" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AUN [P] -->
<variable name="MDMP" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- damping factor of AU6 [P] -->
<variable name="BAROTC" units="minute" initial_value="0.16" private_interface="none" public_interface="out"/> <!-- time constant, baroreceptor (AU6) [P] -->
<variable name="AUK" units="per_minute" initial_value="0.004" private_interface="none" public_interface="out"/> <!-- time constant of baroreceptor adaptation [P] -->
<variable name="AUX" units="dimensionless" initial_value="1" private_interface="none" public_interface="out"/> <!-- sensitivity controller of arterial baroreceptors [P] -->
<variable name="O2CHMO" units="per_mmHg" initial_value="0.01" private_interface="none" public_interface="out"/> <!-- O2 chemoreceptors sensitivity controller [P] -->
<variable name="AUC1" units="dimensionless" initial_value="0.3" private_interface="none" public_interface="out"/> <!-- sensitivity controller of AUC [P] -->
<variable name="CRRFLX" units="mmHg" initial_value="0" private_interface="none" public_interface="out"/> <!-- overriding value of PA1 (if > 0) [P] -->
<variable name="EXE" units="mmHg" initial_value="0" private_interface="none" public_interface="out"/> <!-- driving pressure on autonomic due to exercise [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="autonomics">
<component_ref component="pressure_driving_autonomic_receptors"/>
<component_ref component="chemoreceptors_effect_of_PA"/>
<component_ref component="chemoreceptors_effect_of_art_PO2"/>
<component_ref component="arterial_baroreceptor_reflex"/>
<component_ref component="CNS_ischemic_reflex"/>
<component_ref component="autonomic_response_to_vasculature_pressure"/>
<component_ref component="autonomic_response_to_exercise"/>
<component_ref component="total_autonomic_stimulation"/>
<component_ref component="actual_autonomic_stimulation"/>
<component_ref component="autonomic_drive_on_target_organs_and_tissues"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="autonomics">
<component_ref component="parameter_values"/>
<component_ref component="pressure_driving_autonomic_receptors"/>
<component_ref component="chemoreceptors_effect_of_PA"/>
<component_ref component="chemoreceptors_effect_of_art_PO2"/>
<component_ref component="arterial_baroreceptor_reflex"/>
<component_ref component="CNS_ischemic_reflex"/>
<component_ref component="autonomic_response_to_vasculature_pressure"/>
<component_ref component="autonomic_response_to_exercise"/>
<component_ref component="total_autonomic_stimulation"/>
<component_ref component="actual_autonomic_stimulation"/>
<component_ref component="autonomic_drive_on_target_organs_and_tissues"/>
</component_ref>
</group>
<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<RDF:Description RDF:about="#autonomics_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$QQv43"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$4SdBX3">
<RDF:first RDF:resource="rdf:#$5SdBX3"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$3SdBX3">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$4SdBX3"/>
</RDF:Description>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$5SdBX3" NS1:endingValue="5"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="5" NS1:nonstandard-pointDensity="10000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$d2Cb93" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description RDF:about="#autonomics_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$b2Cb93"/>
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$3SdBX3"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$QQv43">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$RQv43"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$RQv43">
<RDF:first RDF:resource="rdf:#$SQv43"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$b2Cb93">
<NS1:boundIntervals xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$c2Cb93"/>
</RDF:Description>
<RDF:Description RDF:about="rdf:#$c2Cb93">
<RDF:first RDF:resource="rdf:#$d2Cb93"/>
<RDF:rest RDF:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
</RDF:Description>
</RDF:RDF>
</model>
