NhsContractionModel.cpp

/*

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*/
#include "NhsContractionModel.hpp"
#include "OdeSystemInformation.hpp"
#include "EulerIvpOdeSolver.hpp"
#include "UblasCustomFunctions.hpp"

#include <cmath>

//
// Model-scope constant parameters
//
const double NhsContractionModel::mKon = 100;
const double NhsContractionModel::mKrefoff = 0.2;
const double NhsContractionModel::mGamma = 2;
const double NhsContractionModel::mCalciumTroponinMax = 0.07;
const double NhsContractionModel::mAlphaR1 = 0.002;
const double NhsContractionModel::mAlphaR2 = 0.0017;
const double NhsContractionModel::mKZ = 0.15;
const unsigned NhsContractionModel::mNr = 3u;
const double NhsContractionModel::mBeta1 = -4;
const double NhsContractionModel::mAlpha0 = 0.008;
const unsigned NhsContractionModel::mN = 3u;
const double NhsContractionModel::mZp = 0.85;
const double NhsContractionModel::mCalcium50ref = 0.00105;
const double NhsContractionModel::mTref = 56.2;
const double NhsContractionModel::mBeta0 = 4.9;
const double NhsContractionModel::mA = 0.35;
const double NhsContractionModel::mA1 = -29;
const double NhsContractionModel::mA2 = 138;
const double NhsContractionModel::mA3 = 129;
const double NhsContractionModel::mAlpha1 = 0.03;
const double NhsContractionModel::mAlpha2 = 0.130;
const double NhsContractionModel::mAlpha3 = 0.625;


/*
 * ============================== PRIVATE FUNCTIONS =====================================
 */
void NhsContractionModel::CalculateCalciumTrop50()
{
    double Ca50ref_times_one_plus_beta1_times_lam_minus_one = mCalcium50ref * (1 + mBeta1*(mLambda-1));
    double one_plus_beta0_times_lam_minus_one_over_two_gamma = (1 + mBeta0*(mLambda-1))/(2*mGamma);

    mCalciumTrop50 = mCalciumTroponinMax * Ca50ref_times_one_plus_beta1_times_lam_minus_one;
    mCalciumTrop50 /= (Ca50ref_times_one_plus_beta1_times_lam_minus_one + (1-one_plus_beta0_times_lam_minus_one_over_two_gamma)*mKrefoff/mKon);
}


double NhsContractionModel::CalculateT0(double z)
{
    double calcium_ratio_to_n = SmallPow(mCalciumTrop50/mCalciumTroponinMax, mN);

    double z_max = mAlpha0 - mK2*calcium_ratio_to_n;
    z_max /= mAlpha0 + (mAlphaR1 + mK1)*calcium_ratio_to_n;

    return z * mTref * (1+mBeta0*(mLambda-1)) / z_max;
}

/*
 * ============================== PUBLIC FUNCTIONS =====================================
 */

NhsContractionModel::NhsContractionModel()
    :   AbstractOdeBasedContractionModel(5) // five state variables
{
    mpSystemInfo = OdeSystemInformation<NhsContractionModel>::Instance();
    ResetToInitialConditions();

    mLambda = 1.0;
    mDLambdaDt = 0.0;
    mCalciumI = 0.0;

    // Initialise mCalciumTrop50!!
    CalculateCalciumTrop50();

    double zp_to_n_plus_K_to_n = SmallPow(mZp,mNr) + SmallPow(mKZ,mNr);

    mK1 = mAlphaR2 * SmallPow(mZp,mNr-1) * mNr * SmallPow(mKZ,mNr);
    mK1 /= zp_to_n_plus_K_to_n * zp_to_n_plus_K_to_n;

    mK2 = mAlphaR2 * SmallPow(mZp,mNr)/zp_to_n_plus_K_to_n;
    mK2 *= 1 - mNr*SmallPow(mKZ,mNr)/zp_to_n_plus_K_to_n;
}

void NhsContractionModel::SetStretchAndStretchRate(double lambda, double dlambdaDt)
{
    assert(lambda>0.0);
    mLambda = lambda;
    mDLambdaDt = dlambdaDt;
    // lambda changed so update mCalciumTrop50!!
    CalculateCalciumTrop50();
}

void NhsContractionModel::SetInputParameters(ContractionModelInputParameters& rInputParameters)
{
    assert(rInputParameters.intracellularCalciumConcentration != DOUBLE_UNSET);
    assert(rInputParameters.intracellularCalciumConcentration > 0.0);
    mCalciumI = rInputParameters.intracellularCalciumConcentration;
}

void NhsContractionModel::SetIntracellularCalciumConcentration(double calciumConcentration)
{
    assert(calciumConcentration > 0.0);
    mCalciumI = calciumConcentration;
}

double NhsContractionModel::GetCalciumTroponinValue()
{
    return mStateVariables[0];
}

void NhsContractionModel::EvaluateYDerivatives(double time,
                                               const std::vector<double> &rY,
                                               std::vector<double> &rDY)
{

    const double& calcium_troponin = rY[0];
    const double& z = rY[1];
    const double& Q1 = rY[2];
    const double& Q2 = rY[3];
    const double& Q3 = rY[4];

    // check the state vars are in the expected range
    // LCOV_EXCL_START
    if (calcium_troponin < 0)
    {
        EXCEPTION("CalciumTrop concentration went negative");
    }
    if (z<0)
    {
        EXCEPTION("z went negative");
    }
    if (z>1)
    {
        EXCEPTION("z became greater than 1");
    }
    // LCOV_EXCL_STOP


    double Q = Q1 + Q2 + Q3;
    double T0 = CalculateT0(z);

    double Ta;
    if (Q>0)
    {
        Ta = T0*(1+(2+mA)*Q)/(1+Q);
    }
    else
    {
        Ta = T0*(1+mA*Q)/(1-Q);
    }

    rDY[0] =   mKon * mCalciumI * ( mCalciumTroponinMax - calcium_troponin)
             - mKrefoff * (1-Ta/(mGamma*mTref)) * calcium_troponin;

    double ca_trop_to_ca_trop50_ratio_to_n = SmallPow(calcium_troponin/mCalciumTrop50, mN);

    rDY[1] =   mAlpha0 * ca_trop_to_ca_trop50_ratio_to_n * (1-z)
             - mAlphaR1 * z
             - mAlphaR2 * SmallPow(z,mNr) / (SmallPow(z,mNr) + SmallPow(mKZ,mNr));


    rDY[2] = mA1 * mDLambdaDt - mAlpha1 * Q1;
    rDY[3] = mA2 * mDLambdaDt - mAlpha2 * Q2;
    rDY[4] = mA3 * mDLambdaDt - mAlpha3 * Q3;
}


double NhsContractionModel::GetActiveTension()
{
    double T0 = CalculateT0(mStateVariables[1]);
    double Q = mStateVariables[2]+mStateVariables[3]+mStateVariables[4];

    if (Q>0)
    {
        return T0*(1+(2+mA)*Q)/(1+Q);
    }
    else
    {
        return T0*(1+mA*Q)/(1-Q);
    }
}

template<>
void OdeSystemInformation<NhsContractionModel>::Initialise(void)
{
    this->mVariableNames.push_back("CalciumTroponin");
    this->mVariableUnits.push_back("microMols");
    this->mInitialConditions.push_back(0);

    this->mVariableNames.push_back("z");
    this->mVariableUnits.push_back("");
    this->mInitialConditions.push_back(0);

    this->mVariableNames.push_back("Q1");
    this->mVariableUnits.push_back("");
    this->mInitialConditions.push_back(0);

    this->mVariableNames.push_back("Q2");
    this->mVariableUnits.push_back("");
    this->mInitialConditions.push_back(0);

    this->mVariableNames.push_back("Q3");
    this->mVariableUnits.push_back("");
    this->mInitialConditions.push_back(0);

    this->mInitialised = true;
}