<?xml version="1.0" encoding="utf-8"?>
<model
name="muscle_autoregulatory_local_blood_flow_control_CellML1_0_model"
cmeta:id="muscle_autoregulatory_local_blood_flow_control_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: muscle_autoregulatory_local_blood_flow_control</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 been validated. 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). This may effect the transient behaviour of the model, however
the steady-state behaviour would remain the same. The equations in this file and the steady-state output from
the model conform to the results from the MODSIM program.
</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>
The circulatory system is divided into three separate parts for blood flow control:(1) the kidneys which are presented in an
entirely separate CellML model; (2) non-muscle local blood flow control; and (3) muscle local blood flow control. This
particular CellML model describes muscle autoregulatory local blood flow control. Autoregulation in the muscles is similar
to that in the non-muscle tissues except that only two parallel autoregulatory circuits are given. One of these is an extremely
short-term autoregulatory circuit that allows rapid adjustment of muscle blood flow to muscle metabolism during muscle activity,
and the other is a very long-term autoregulatory circuit.
</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="muscle_autoregulatory_local_blood_flow_control_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="m_blood_flow.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the components and processes described in the current CellML model.</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="#muscle_autoregulatory_local_blood_flow_control_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>Muscle Blood Flow Control</vCard:Family>
<vCard:Given></vCard:Given>
<vCard:Other></vCard:Other>
</vCard:N>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Description of Guyton muscle blood flow control 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>muscle blood flow</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="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="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="#muscle_autoregulatory_local_blood_flow_control_CellML1_0_model">
<rdf:value>
The circulatory system is divided into three separate parts for blood flow control:
(1) the kidneys which are presented in an entirely separate section of this model;
(2) non-muscle local blood flow control; and (3) muscle local blood flow control.
Muscle Autoregulatory Local Blood Flow Control
Autoregulation in the muscles is similar to that in the non-muscle tissues except
that only two parallel autoregulatory circuits are given. One of these is an
extremely short-term autoregulatory circuit that allows rapid adjustment of muscle
blood flow to muscle metabolism during muscle activity, and the other is a very
long-term autoregulatory circuit.
</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>
<!-- ======================================== MUSCLE AUTOREGULATORY LOCAL BLOOD FLOW CONTROL TOP-LEVEL COMPONENT ============================================= -->
<component name="muscle_autoregulatory_local_blood_flow_control"
cmeta:id="muscle_autoregulatory_local_blood_flow_control">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#muscle_autoregulatory_local_blood_flow_control">
<rdf:value>
Encapsulation grouping component containing all the components in the Muscle Autoregulatory Local Blood
Flow Control Model. The inputs and outputs of the Muscle Autoregulatory Local Blood Flow Control 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="PMO" initial_value="38.0666" units="mmHg" private_interface="out" public_interface="none"/>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="muscle_autoregulatory_local_blood_flow_control" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== MUSCLE AUTOREGULATORY DRIVING FORCE ============================================= -->
<component name="M_autoregulatory_driving_force"
cmeta:id="M_autoregulatory_driving_force">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_autoregulatory_driving_force">
<rdf:value>
ARM1:
Calculation of the driving force for autoregulation in the muscles (PDO) by subtracting
a set-point value from the pressure of oxygen in the muscle tissues (PMO).
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM1">
<rdf:value>
ARM1:
Calculation of the driving force for autoregulation in the muscles (PDO) by subtracting
a set-point value from the pressure of oxygen in the muscle tissues (PMO).
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PMO" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="PDO" units="mmHg" private_interface="none" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM1">
<eq/>
<ci>PDO</ci>
<apply>
<minus/>
<ci>PMO</ci>
<cn cellml:units="mmHg">38</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="M_autoregulatory_driving_force" component_2="muscle_autoregulatory_local_blood_flow_control"/>
<map_variables variable_1="PMO" variable_2="PMO"/>
</connection>
<!-- ======================================== MUSCLE SHORT-TERM AUTOREGULATION ============================================= -->
<component name="M_short_term_autoregulation"
cmeta:id="M_short_term_autoregulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_short_term_autoregulation">
<rdf:value>
Containment grouping component for "M_ST_sensitivity_control" and "M_ST_time_delay_and_damping".
</rdf:value>
</rdf:Description>
</rdf:RDF>
</component>
<!-- ======================================== MUSCLE SHORT_TERM SENSITIVITY CONTROL ============================================= -->
<component name="M_ST_sensitivity_control"
cmeta:id="M_ST_sensitivity_control">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_ST_sensitivity_control">
<rdf:value>
ARM2 and ARM3:
Sensitivity control for the short-term muscle autoregulation, controlled by the
variable (POM), and the driving output oxygen pressure is the variable POE.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM2_and_ARM3">
<rdf:value>
ARM2 and ARM3:
Sensitivity control for the short-term muscle autoregulation, controlled by the
variable (POM), and the driving output oxygen pressure is the variable POE.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PDO" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="POE" units="mmHg" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="POM" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM2_and_ARM3">
<eq/>
<ci>POE</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>PDO</ci>
<ci>POM</ci>
</apply>
<cn cellml:units="mmHg">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="M_ST_sensitivity_control" component_2="M_autoregulatory_driving_force"/>
<map_variables variable_1="PDO" variable_2="PDO"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="M_ST_sensitivity_control" component_2="parameter_values"/>
<map_variables variable_1="POM" variable_2="POM"/>
</connection>
<!-- ======================================== MUSCLE SHORT-TERM TIME-DELAY AND LOWER LIMIT ============================================= -->
<component name="M_ST_time_delay_and_limit"
cmeta:id="M_ST_time_delay_and_limit">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_ST_time_delay_and_limit">
<rdf:value>
ARM5, ARM6, and ARM7:
Time delay mechanism for the rapid autoregulation, allowing the output of
Block ARM7 (AMM1) to approach POE with a time constant of A4K.
ARM7A:
This sets a lower limit (AMM4) for the variable AMM1.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM5_to_ARM7">
<rdf:value>
ARM5, ARM6, and ARM7:
Time delay mechanism for the rapid autoregulation, allowing the output of
Block ARM7 (AMM1) to approach POE with a time constant of A4K.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM7A">
<rdf:value>
ARM7A:
This sets a lower limit (AMM4) for the variable AMM1.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="POE" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="M_ST_time_delay_and_limit_AMM1"
name="AMM1" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="A4K" units="minute" private_interface="none" public_interface="in"/>
<variable name="AMM4" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AMM1T" initial_value="1.00269" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM5_to_ARM7">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AMM1T</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci>POE</ci>
<cn cellml:units="per_mmHg">1</cn>
</apply>
<ci>AMM1T</ci>
</apply>
<ci>A4K</ci>
</apply>
</apply>
<apply id="ARM7A">
<eq/>
<ci>AMM1</ci>
<piecewise>
<piece>
<ci>AMM4</ci>
<apply>
<lt/>
<ci>AMM1T</ci>
<ci>AMM4</ci>
</apply>
</piece>
<otherwise>
<ci>AMM1T</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="M_ST_time_delay_and_limit" component_2="M_ST_sensitivity_control"/>
<map_variables variable_1="POE" variable_2="POE"/>
</connection>
<connection>
<map_components component_1="M_ST_time_delay_and_limit" component_2="muscle_autoregulatory_local_blood_flow_control"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="M_ST_time_delay_and_limit" component_2="parameter_values"/>
<map_variables variable_1="A4K" variable_2="A4K"/>
<map_variables variable_1="AMM4" variable_2="AMM4"/>
</connection>
<!-- ======================================== MUSCLE LONG-TERM AUTOREGULATION ============================================= -->
<component name="M_long_term_autoregulation"
cmeta:id="M_long_term_autoregulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_long_term_autoregulation">
<rdf:value>
Containment grouping component for "M_LT_sensitivity_control" and
"M_LT_time_delay".
</rdf:value>
</rdf:Description>
</rdf:RDF>
</component>
<!-- ======================================== MUSCLE LONG-TERM SENSITIVITY CONTROL ============================================= -->
<component name="M_LT_sensitivity_control"
cmeta:id="M_LT_sensitivity_control">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_LT_sensitivity_control">
<rdf:value>
ARM8:
Sensitivity control for controlling the long-term autoregulation in the muscles.
The variable that controls the sensitivity is POM2.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM8_and_part_ARM9">
<rdf:value>
ARM8:
Sensitivity control for controlling the long-term autoregulation in the muscles.
The variable that controls the sensitivity is POM2.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PDO" units="mmHg" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="POF" units="mmHg" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="POM2" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM8_and_part_ARM9">
<eq/>
<ci>POF</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>POM2</ci>
<ci>PDO</ci>
</apply>
<cn cellml:units="mmHg">1</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="M_LT_sensitivity_control" component_2="M_autoregulatory_driving_force"/>
<map_variables variable_1="PDO" variable_2="PDO"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="M_LT_sensitivity_control" component_2="parameter_values"/>
<map_variables variable_1="POM2" variable_2="POM2"/>
</connection>
<!-- ======================================== MUSCLE LONG-TERM TIME DELAY ============================================= -->
<component name="M_LT_time_delay"
cmeta:id="M_LT_time_delay">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#M_LT_time_delay">
<rdf:value>
ARM9, ARM10, and ARM11:
Time delay system for long-term autoregulation in muscle with a time constant
equal to A4K2 and an output of AMM2.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM9_cont_to_ARM11">
<rdf:value>
ARM9, ARM10, and ARM11:
Time delay system for long-term autoregulation in muscle with a time constant
equal to A4K2 and an output of AMM2.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="POF" units="mmHg" private_interface="none" public_interface="in"/>
<variable name="time" units="minute" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="M_LT_time_delay_AMM2"
name="AMM2" initial_value="1.09071" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="A4K2" units="minute" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM9_cont_to_ARM11">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AMM2</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci>POF</ci>
<cn cellml:units="per_mmHg">1</cn>
</apply>
<ci>AMM2</ci>
</apply>
<ci>A4K2</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="M_LT_time_delay" component_2="M_LT_sensitivity_control"/>
<map_variables variable_1="POF" variable_2="POF"/>
</connection>
<connection>
<map_components component_1="M_LT_time_delay" component_2="muscle_autoregulatory_local_blood_flow_control"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="M_LT_time_delay" component_2="parameter_values"/>
<map_variables variable_1="A4K2" variable_2="A4K2"/>
</connection>
<!-- ======================================== GLOBAL MUSCLE BLOOD FLOW AUTOREGULATION OUTPUT ============================================= -->
<component name="global_M_blood_flow_autoregulation_output"
cmeta:id="global_M_blood_flow_autoregulation_output">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#global_M_blood_flow_autoregulation_output">
<rdf:value>
ARM12:
Multiplication of the outputs of the two parallel muscle autoregulatory
systems (AMM1 and AMM2) to given an overall multiplier factor for muscle
autoregulation (AMM) that in turn controls vascular resistance in the muscles.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ARM12">
<rdf:value>
ARM12:
Multiplication of the outputs of the two parallel muscle autoregulatory
systems (AMM1 and AMM2) to given an overall multiplier factor for muscle
autoregulation (AMM) that in turn controls vascular resistance in the muscles.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="AMM1" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="AMM2" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable cmeta:id="global_M_blood_flow_autoregulation_output_AMM"
name="AMM" units="dimensionless" private_interface="none" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ARM12">
<eq/>
<ci>AMM</ci>
<apply>
<times/>
<ci>AMM1</ci>
<ci>AMM2</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="global_M_blood_flow_autoregulation_output" component_2="M_ST_time_delay_and_limit"/>
<map_variables variable_1="AMM1" variable_2="AMM1"/>
</connection>
<connection>
<map_components component_1="global_M_blood_flow_autoregulation_output" component_2="M_LT_time_delay"/>
<map_variables variable_1="AMM2" variable_2="AMM2"/>
</connection>
<!-- ========================================================== PARAMETER VALUES ================================================================ -->
<component name="parameter_values"
cmeta:id="parameter_values">
<variable name="POM" units="dimensionless" initial_value="0.04" private_interface="none" public_interface="out"/> <!-- sensitivity control, rapid muscle autoregulation [P] -->
<variable name="A4K" units="minute" initial_value="0.1" private_interface="none" public_interface="out"/> <!-- time constant, rapid muscle autoregulation [P] -->
<variable name="AMM4" units="dimensionless" initial_value="0.005" private_interface="none" public_interface="out"/> <!-- AMM1 lower limit [P] -->
<variable name="POM2" units="dimensionless" initial_value="2" private_interface="none" public_interface="out"/> <!-- sensitivity control, long-term muscle autoregulation [P] -->
<variable name="A4K2" units="minute" initial_value="40000" private_interface="none" public_interface="out"/> <!-- time constant, long-term muscle autoregulation [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="muscle_autoregulatory_local_blood_flow_control">
<component_ref component="M_autoregulatory_driving_force"/>
<component_ref component="M_short_term_autoregulation">
<component_ref component="M_ST_sensitivity_control"/>
<component_ref component="M_ST_time_delay_and_limit"/>
</component_ref>
<component_ref component="M_long_term_autoregulation">
<component_ref component="M_LT_sensitivity_control"/>
<component_ref component="M_LT_time_delay"/>
</component_ref>
<component_ref component="global_M_blood_flow_autoregulation_output"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="muscle_autoregulatory_local_blood_flow_control">
<component_ref component="parameter_values"/>
<component_ref component="M_autoregulatory_driving_force"/>
<component_ref component="M_short_term_autoregulation"/>
<component_ref component="M_ST_sensitivity_control"/>
<component_ref component="M_ST_time_delay_and_limit"/>
<component_ref component="M_long_term_autoregulation"/>
<component_ref component="M_LT_sensitivity_control"/>
<component_ref component="M_LT_time_delay"/>
<component_ref component="global_M_blood_flow_autoregulation_output"/>
</component_ref>
</group>
<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<RDF:Description RDF:about="#muscle_autoregulatory_local_blood_flow_control_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:#$5SdBX3" NS1:endingValue="500000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="500000" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$d2Cb93" NS1:nonstandard-pointDensity="100000"/>
<RDF:Description RDF:about="#muscle_autoregulatory_local_blood_flow_control_CellML1_0_model">
<NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$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>
