Location: Guyton, Atrial, Natriuretic, Peptide, 2008 @ e955eb75c5c4 / guyton_atrial_natriuretic_peptide_2008.cellml

Author:
jonna <devnull@localhost>
Date:
2009-07-16 14:55:08+12:00
Desc:
Added General Files. Changed links of dependencies so can open from web-browser. Added RDF metadata for citation and keywords, removed publication link from documentation.
Permanent Source URI:
http://models.cellml.org/workspace/guyton_atrial_natriuretic_peptide_2008/rawfile/e955eb75c5c423288497d8f7b3b90bbaaca73e7c/guyton_atrial_natriuretic_peptide_2008.cellml

<?xml version="1.0" encoding="utf-8"?>
<model 
	name="atrial_natriuretic_peptide_CellML1_0_model"
	cmeta:id="atrial_natriuretic_peptide_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: Atrial Natriuretic Peptide</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>
This particular CellML model describes the control of atrial natriuretic peptide secretion by the left and right atria of 
the heart.  It also calculates a multiplier factor for controlling the resistance of the afferent arterioles (AAR) of the kidneys.
</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="atrial_natriuretic_peptide_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="atrial_natriuretic_peptide.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&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=4334846&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>

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


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      <!--
        The Model Builder Metadata.  The Dublin Core "creator" element is used  
        to indicate the person who translated the model into CellML.
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        <vCard:N rdf:parseType="Resource">
          <vCard:Family>Terkildsen</vCard:Family>
          <vCard:Given>Jonna</vCard:Given>
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          <rdf:value>j.terkildsen@auckland.ac.nz</rdf:value>
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        </vCard:EMAIL>
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          <vCard:Orgname>The University of Auckland</vCard:Orgname>
          <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
        </vCard:ORG>
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      <!--
        The Creation Date metadata. This is the date on which the model
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      <dcterms:created rdf:parseType="Resource">
        <dcterms:W3CDTF>2008-04-03</dcterms:W3CDTF>
      </dcterms:created>
      
      <!--
        The Modification History metadata. This lists the changes that have been
        made to the document, who made the changes, and when they were made.
      -->
      
      <!-- The Publisher metadata. -->
      <dc:publisher>
        The University of Auckland, Bioengineering Institute
      </dc:publisher>
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<!-- =======================================================    CITATION AND KEYWORD METADATA    ================================================== -->

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			xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
		<rdf:Description rdf:about="#atrial_natriuretic_peptide_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>Atrial Natriuretic Peptide</vCard:Family>
									<vCard:Given></vCard:Given>
									<vCard:Other></vCard:Other>
								</vCard:N>
							</rdf:li>

						</rdf:Seq>
					</dc:creator>
					<dc:title>Description of Guyton atrial natriuretic peptide module</dc:title>
					<bqs:volume />
					<bqs:first_page />
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						<dc:title></dc:title>
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						<dcterms:W3CDTF>2008-00-00 00:00</dcterms:W3CDTF>
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						<rdf:li>physiology</rdf:li>
						<rdf:li>organ systems</rdf:li>
						<rdf:li>cardiovascular circulation</rdf:li>
						<rdf:li>vatrial natriuretic peptide</rdf:li>
						<rdf:li>Guyton</rdf:li>
					</rdf:Bag>
					</rdf:value>
				</dc:subject>
			</bqs:reference>
		</rdf:Description>
	</rdf:RDF>

  
  
<!-- ======================================================= 		UNITS		================================================== -->

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      <unit multiplier="60" units="second"/>
   </units>
   <units name="per_minute">
      <unit units="minute" exponent="-1"/>
   </units>
   <units name="beats_per_minute">
      <unit units="minute" exponent="-1"/>
   </units>
   <units name="beats_per_minute_per_mmHg">
      <unit units="minute" exponent="-1"/>
      <unit units="mmHg" exponent="-1"/>
   </units>
   <units name="minute_per_L">
      <unit units="minute"/>
      <unit units="litre" 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="mOsm">
      <unit units="mole" prefix="milli"/>
   </units>
   <units name="mOsm_per_litre">
      <unit units="mole" prefix="milli"/>
      <unit units="litre" exponent="-1"/>
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   <units name="mOsm_per_minute">
      <unit units="mole" prefix="milli"/>
      <unit units="minute" exponent="-1"/>
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   <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="per_mmHg_per_minute">
      <unit units="mmHg" exponent="-1"/>
      <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="mmHg_L_per_minute">
      <unit units="litre"/>
      <unit units="mmHg"/>
      <unit units="minute" 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"/>
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      <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="L_per_mmHg">
      <unit units="mmHg" 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>
   <units name="L_per_minute_per_mmHg2">
      <unit units="litre"/>
      <unit units="minute" exponent="-1"/>
      <unit units="mmHg" exponent="-2"/>
   </units>

<!-- =================================================================================================================== -->


	<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
		<rdf:Description rdf:about="#atrial_natriuretic_peptide_CellML1_0_model">
			<rdf:value>
			This section calculates the control of atrial natriuretic peptide secretion by the 
			left and right atria of the heart.  It also calculates a multiplier factor for 
			controlling the resistance of the afferent arterioles (AAR) of the kidneys.
			</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>


<!-- ========================================	ATRIAL NATRIURETIC PEPTIDE TOP-LEVEL COMPONENT	============================================= -->
	<component 	name="atrial_natriuretic_peptide" 
				cmeta:id="atrial_natriuretic_peptide">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#atrial_natriuretic_peptide">
				<rdf:value>
				Encapsulation grouping component containing all the components in the Atrial Natriuretic Peptide Model.  
				The inputs and outputs of the Atrial Natriuretic Peptide 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="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"/>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="atrial_natriuretic_peptide" component_2="environment"/>
		<map_variables variable_1="time" variable_2="time"/>
	</connection>

<!-- ========================================	TOTAL ATRIAL NATRIURETIC PEPTIDE SECRETED	============================================= -->
	<component 	name="total_ANP_secreted" 
				cmeta:id="total_ANP_secreted">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#total_ANP_secreted">
				<rdf:value>
				ANP1, ANP2, ANP3, ANP3A, and ANP4:  
				Calculation of the total amount of atrial natriuretic peptide secreted at 
				any given time.  Block ANP1 determines the pressure level at which changes 
				in left atrial pressure (PLA) will begin to affect atrinatriuretic peptide 
				secretion.  Block 1A sets a lower limit of zero for this secretion.  
				Block ANP2 calculates from the pressure level in the right atrium (PRA) the 
				stimulation of ANP output by the right atrium.  Block 3 multiplies the 
				output of the right atrium by two-fold (against a one-fold amount secreted 
				by the left atrium).  Block 3A sets a lower limit of zero for right atrial 
				output.  Block 4 adds the outputs from the left atrium and right atrium.

				ANP5:  
				Block 5 normalizes the ANP secretion under normal conditions to a value of 1.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP1_and_ANP1A">
				<rdf:value>
				ANP1, ANP2, ANP3 and ANP3A:  
				Calculation of the total amount of atrial natriuretic peptide secreted at 
				any given time.  Block ANP1 determines the pressure level at which changes 
				in left atrial pressure (PLA) will begin to affect atrinatriuretic peptide 
				secretion.  Block 1A sets a lower limit of zero for this secretion.  
				Block ANP2 calculates from the pressure level in the right atrium (PRA) the 
				stimulation of ANP output by the right atrium.  Block 3 multiplies the 
				output of the right atrium by two-fold (against a one-fold amount secreted 
				by the left atrium).  Block 3A sets a lower limit of zero for right atrial 
				output. 
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP2_ANP3_and_ANP3A">
				<rdf:value>
				ANP1, ANP2, ANP3 and ANP3A:  
				Calculation of the total amount of atrial natriuretic peptide secreted at 
				any given time.  Block ANP1 determines the pressure level at which changes 
				in left atrial pressure (PLA) will begin to affect atrinatriuretic peptide 
				secretion.  Block 1A sets a lower limit of zero for this secretion.  
				Block ANP2 calculates from the pressure level in the right atrium (PRA) the 
				stimulation of ANP output by the right atrium.  Block 3 multiplies the 
				output of the right atrium by two-fold (against a one-fold amount secreted 
				by the left atrium).  Block 3A sets a lower limit of zero for right atrial 
				output. 
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP4_and_ANP5">
				<rdf:value>
				ANP4 and ANP5:  
				Block 4 adds the outputs from the left atrium and right atrium.  Block 5 normalizes 
				the ANP secretion under normal conditions to a value of 1.
				</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"/>

<!-- Outputs to other components -->
		<variable name="ANP" 	units="dimensionless" private_interface="none" public_interface="out"/>

<!-- Internal variables -->
		<variable name="ANPL"	units="dimensionless" private_interface="none" public_interface="none"/>
		<variable name="ANPR2"	units="dimensionless" private_interface="none" public_interface="none"/>

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="ANP1_and_ANP1A">
				<eq/>
				<ci>ANPL</ci>
				<piecewise>
					<piece>
						<cn cellml:units="dimensionless">0</cn>
						<apply>
							<lt/>
							<apply>
								<times/>
								<apply>
									<minus/>
									<ci>PLA</ci>
									<cn cellml:units="mmHg">1</cn>
								</apply>
								<cn cellml:units="per_mmHg">1</cn>
							</apply>
							<cn cellml:units="dimensionless">0</cn>
						</apply>
					</piece>
					<otherwise>
						<apply>
							<times/>
							<apply>
								<minus/>
								<ci>PLA</ci>
								<cn cellml:units="mmHg">1</cn>
							</apply>
							<cn cellml:units="per_mmHg">1</cn>
						</apply>
					</otherwise>
				</piecewise>
			</apply>
			<apply id="ANP2_ANP3_and_ANP3A">
				<eq/>
				<ci>ANPR2</ci>
				<piecewise>
					<piece>
						<cn cellml:units="dimensionless">0</cn>
						<apply>
							<lt/>
							<apply>
								<times/>
								<apply>
									<plus/>
									<ci>PRA</ci>
									<cn cellml:units="mmHg">1</cn>
								</apply>
								<cn cellml:units="per_mmHg">2</cn>
							</apply>
							<cn cellml:units="dimensionless">0</cn>
						</apply>
					</piece>
					<otherwise>
						<apply>
							<times/>
							<apply>
								<plus/>
								<ci>PRA</ci>
								<cn cellml:units="mmHg">1</cn>
							</apply>
							<cn cellml:units="per_mmHg">2</cn>
						</apply>
					</otherwise>
				</piecewise>
			</apply>
			<apply id="ANP4_and_ANP5">
				<eq/>
				<ci>ANP</ci>
				<apply>
					<divide/>
					<apply>
						<plus/>
						<ci>ANPL</ci>
						<ci>ANPR2</ci>
					</apply>
					<cn cellml:units="dimensionless">3</cn>
				</apply>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="total_ANP_secreted" component_2="atrial_natriuretic_peptide"/>
		<map_variables variable_1="PLA" variable_2="PLA"/>
		<map_variables variable_1="PRA" variable_2="PRA"/>
	</connection>

<!-- ========================================	ATRIAL NATRIURETIC PEPTIDE INTO CIRCULATION	============================================= -->
	<component 	name="ANP_into_circulation" 
				cmeta:id="ANP_into_circulation">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#ANP_into_circulation">
				<rdf:value>
				ANP 7:  
				This block allows infusion of ANP into the circulation (ANPINF).  The output 
				of the block is ANP1 which is the total rate of ANP entering the circulation 
				at any given time.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP7">
				<rdf:value>
				ANP 7:  
				This block allows infusion of ANP into the circulation (ANPINF).  The output 
				of the block is ANP1 which is the total rate of ANP entering the circulation 
				at any given time.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="ANP"	units="dimensionless" private_interface="none" public_interface="in"/>

<!-- Outputs to other components -->
		<variable name="ANP1" 	units="dimensionless" private_interface="none" public_interface="out"/>

<!-- Parameters from parameter_file -->
		<variable name="ANPKNS"	units="dimensionless" private_interface="none" public_interface="in"/>
		<variable name="ANPINF"	units="dimensionless" private_interface="none" public_interface="in"/>

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="ANP7">
				<eq/>
				<ci>ANP1</ci>
				<piecewise>
					<piece>
						<ci>ANPKNS</ci>
						<apply>
							<gt/>
							<ci>ANPKNS</ci>
							<cn cellml:units="dimensionless">0</cn>
						</apply>
					</piece>
					<otherwise>
						<apply>
							<plus/>
							<ci>ANP</ci>
							<ci>ANPINF</ci>
						</apply>
					</otherwise>
				</piecewise>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_into_circulation" component_2="total_ANP_secreted"/>
		<map_variables variable_1="ANP" variable_2="ANP"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_into_circulation" component_2="parameter_values"/>
		<map_variables variable_1="ANPKNS" variable_2="ANPKNS"/>
		<map_variables variable_1="ANPINF" variable_2="ANPINF"/>
	</connection>

<!-- ========================================	ATRIAL NATRIURETIC PEPTIDE IN PLASMA	============================================= -->
<!-- ========================================	CHECK THIS EQUATION! REMOVED DAMPING FROM DE!!!	============================================= -->
	<component 	name="ANP_in_plasma" 
				cmeta:id="ANP_in_plasma">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#ANP_in_plasma">
				<rdf:value>
				ANP8, ANP9, and ANP10:  
				Calculation of the concentration of ANP in the plasma (ANPC) from the rate of 
				entry of ANP into the plasma (ANP1).  The time constant for build-up of ANP in 
				the circulation is determined by ANPTC in Block 9.  ANPC is normalized to 1.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP8_to_ANP10">
				<rdf:value>
				ANP8, ANP9, and ANP10:  
				Calculation of the concentration of ANP in the plasma (ANPC) from the rate of 
				entry of ANP into the plasma (ANP1).  The time constant for build-up of ANP in 
				the circulation is determined by ANPTC in Block 9.  ANPC is normalized to 1.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="ANP1"	units="dimensionless" private_interface="none" public_interface="in"/>
		<variable name="time"	units="minute" private_interface="none" public_interface="in"/>

<!-- Outputs to other components -->
		<variable name="ANPC" 	initial_value="1.0"	units="dimensionless" private_interface="none" public_interface="out"/>

<!-- Parameters from parameter_file -->
		<variable name="ANPTC"	units="minute" private_interface="none" public_interface="in"/>

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="ANP8_to_ANP10">
				<eq/>
				<apply>
					<diff/>
					<bvar>
						<ci>time</ci>
					</bvar>
					<ci>ANPC</ci>
				</apply>
				<apply>
					<divide/>
					<apply>
						<minus/>
						<ci>ANP1</ci>
						<ci>ANPC</ci>
					</apply>
					<ci>ANPTC</ci>
				</apply>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_in_plasma" component_2="ANP_into_circulation"/>
		<map_variables variable_1="ANP1" variable_2="ANP1"/>
	</connection>
	<connection>
		<map_components component_1="ANP_in_plasma" component_2="atrial_natriuretic_peptide"/>
		<map_variables variable_1="time" variable_2="time"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_in_plasma" component_2="parameter_values"/>
		<map_variables variable_1="ANPTC" variable_2="ANPTC"/>
	</connection>

<!-- ========================================	ANP EFFECT ON RENAL AFFERENT ARTERIOLAR RESISTANCE	============================================= -->
	<component 	name="ANP_effect_on_renal_afferent_arteriolar_resistance" 
				cmeta:id="ANP_effect_on_renal_afferent_arteriolar_resistance">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#ANP_effect_on_renal_afferent_arteriolar_resistance">
				<rdf:value>
				ANP11:  
				This curve calculates a multiplier factor (ANPX) for determining the effect 
				of ANP on the afferent arteriolar resistance of the kidneys.  The upper limit 
				of ANPX is ANPXUL.  

				ANP 12:  
				This block sets the lower limit of ANPX equal to -1.
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP11">
				<rdf:value>
				ANP11:  
				This curve calculates a multiplier factor (ANPX) for determining the effect 
				of ANP on the afferent arteriolar resistance of the kidneys.  The upper limit 
				of ANPX is ANPXUL.  
				</rdf:value>
			</rdf:Description>
			<rdf:Description rdf:about="#ANP12">
				<rdf:value>
				ANP 12:  
				This block sets the lower limit of ANPX equal to -1.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
<!-- Inputs from other components -->
		<variable name="ANPC"	units="dimensionless" private_interface="none" public_interface="in"/>

<!-- Outputs to other components -->
		<variable 	cmeta:id="ANP_effect_on_renal_afferent_arteriolar_resistance_ANPX"
					name="ANPX" 	units="dimensionless" private_interface="none" public_interface="out"/>

<!-- Parameters from parameter_file -->
		<variable name="ANPXUL"	units="dimensionless" private_interface="none" public_interface="in"/>

<!-- Internal variables -->
		<variable name="ANPX1"	units="dimensionless" private_interface="none" public_interface="none"/>

		<math xmlns="http://www.w3.org/1998/Math/MathML">
			<apply id="ANP11">
				<eq/>
				<ci>ANPX1</ci>
				<apply>
					<minus/>
					<ci>ANPXUL</ci>
					<apply>
						<divide/>
						<ci>ANPXUL</ci>
						<apply>
							<times/>
							<cn cellml:units="dimensionless">0.5555556</cn>
							<apply>
								<plus/>
								<cn cellml:units="dimensionless">1</cn>
								<ci>ANPC</ci>
							</apply>
						</apply>
					</apply>
				</apply>
			</apply>
			<apply id="ANP12">
				<eq/>
				<ci>ANPX</ci>
				<piecewise>
					<piece>
						<apply>
							<minus/>
							<cn cellml:units="dimensionless">1</cn>
						</apply>
						<apply>
							<lt/>
							<ci>ANPX1</ci>
							<apply>
								<minus/>
								<cn cellml:units="dimensionless">1</cn>
							</apply>
						</apply>
					</piece>
					<otherwise>
						<ci>ANPX1</ci>
					</otherwise>
				</piecewise>
			</apply>
		</math>
	</component>

<!-- INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_effect_on_renal_afferent_arteriolar_resistance" component_2="ANP_in_plasma"/>
		<map_variables variable_1="ANPC" variable_2="ANPC"/>
	</connection>

<!-- PARAMETER CONNECTIONS -->
	<connection>
		<map_components component_1="ANP_effect_on_renal_afferent_arteriolar_resistance" component_2="parameter_values"/>
		<map_variables variable_1="ANPXUL" variable_2="ANPXUL"/>
	</connection>

	<component 	name="parameter_values"
				cmeta:id="parameter_values">
      <variable name="ANPKNS" 	units="dimensionless" 	initial_value="0"			private_interface="none"	public_interface="out"/>	<!-- overriding value of ANP secretion rate -->
      <variable name="ANPINF" 	units="dimensionless" 	initial_value="0"			private_interface="none"	public_interface="out"/>	<!-- rate of exogenous ANP infusion -->
      <variable name="ANPTC" 	units="minute" 	initial_value="4"			private_interface="none"	public_interface="out"/>	<!-- time constant, ANP accumulation and destruction [P] -->
      <variable name="ANPXUL" 	units="dimensionless" 	initial_value="10"			private_interface="none"	public_interface="out"/>	<!-- ANPX upper limit [P] -->
	</component>

<!-- ============================================================		GROUPING		=============================================================== -->
   <group>
      <relationship_ref relationship="containment"/>
      <component_ref component="atrial_natriuretic_peptide">
			<component_ref component="total_ANP_secreted"/>
			<component_ref component="ANP_into_circulation"/>
			<component_ref component="ANP_in_plasma"/>
			<component_ref component="ANP_effect_on_renal_afferent_arteriolar_resistance"/>
      </component_ref>
   </group>
      
   <group>
      <relationship_ref relationship="encapsulation"/>
      <component_ref component="atrial_natriuretic_peptide">
			<component_ref component="parameter_values"/>
			<component_ref component="total_ANP_secreted"/>
			<component_ref component="ANP_into_circulation"/>
			<component_ref component="ANP_in_plasma"/>
			<component_ref component="ANP_effect_on_renal_afferent_arteriolar_resistance"/>
      </component_ref>
   </group>


<!-- SIMULATION METADATA -->
<RDF:RDF xmlns:RDF="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
  <RDF:Description RDF:about="#atrial_natriuretic_peptide_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:#$5SdBX3" NS1:endingValue="100"/>
  <RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$SQv43" NS1:endingValue="100" NS1:nonstandard-pointDensity="10000"/>
  <RDF:Description xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:about="rdf:#$d2Cb93" NS1:nonstandard-pointDensity="100000"/>
  <RDF:Description RDF:about="#atrial_natriuretic_peptide_CellML1_0_model#LfY7zdZ%60EYs">
    <NS1:simulation xmlns:NS1="http://www.cellml.org/metadata/simulation/1.0#" RDF:resource="rdf:#$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>