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A Cardiovascular Simulator for Research User's Manual

1. 5 Ramakrishna Mukkamala and Richard J Cohen A forward model based validation of car diovascular system identification Am J Physiol 281 H2714 H2730 2001 6 Ramakrishna Mukkamala Joanne M Mathias Thomas J Mullen Richard J Cohen and Roy Freeman System identification of closed loop cardiovascular control mechanisms Diabetic autonomic neuropathy Am J Physiol 276 R905 R912 1999 7 Ramakrishna Mukkamala Derin A Sherman Roger G Mark and Richard J Cohen A nonlinear computational model of the pulsatile heart and circulation Submitted to Am J Physiol 8 Ramakrishna Mukkamala Karin Toska and Richard J Cohen Noninvasive identification of the total peripheral resistance baroreflex Am J Physiol 284 3 H947 H959 2003 9 Thomas J Mullen Marvin L Appel Ramakrishna Mukkamala Joanne M Mathias and Richard J Cohen System identification of closed loop cardiovascular control Effects of posture and autonomic blockade Am J Physiol 272 H448 H461 1997 10 Bruce Pomeranz Robert J B Macaulay Margaret A Caudill Ilan Kutz Daniel C Shannon Richard J Cohen and Herbert Benson Assessment of autonomic function in humans by heart rate spectral analysis Am J Physiol 248 17 H151 H153 1985 54
2. Download the data in the metronomic breathing group from the bottom of this web page M hea and M qrs where ranges from 1 to 14 These data provide the qrs times of 14 volunteer subjects in the supine posture breathing at a fixed rate of 0 25 Hz Calculate an instantaneous heart rate tachogram from the qrs times for each subject by executing the following command at the Linux prompt 14 times tach r M a qrs f gt hr Note that tach is open source software provided by PhysioNet Type tach h at the Linux prompt for help b ww c ww d Calculate the maximum entropy power spectrum of the instantaneous heart rate tachogram for each subject by executing the following command at the Linux prompt 14 times memse f 2 Z o 15 hr gt phr Note that memse is open source software provided by PhysioNet Type memse h at the Linux prompt for help The generated files phr are two column ASCII format files in which the first column represents frequencies and the second column represents the corresponding power spectral densities ww Average the power spectra over the 14 subjects and write the averaged spectra to a two column ASCII file called avephr by writing a simple program or using any pre existing software such as MATLAB f Plot the averaged power spectrum by executing the following command at the Linux prompt plot2d avephr 0 1 Note that plot2d which is a simple program that controls Gnuplot is
3. Off line display of left ventricle pressure versus volume Uncontrolled unperturbed intact pulsatile heart and circulation with default parameter values e Required Steps 27 Record temp File v View Edit Properties 7 lt Search lt lt lt Find gt gt gt Search gt Help Quit UUW AMADA 0 20 Grid intervals 0 2 sec x 0 5 mV Figure 10 Initial WAVE window generated according to Ex and Ex 2 28 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters 2 2 Open the file parameters_2 with any text editor e g emacs 3 Re assign the following parameter waveform 1 Make sure all of the status parame ters are assigned the numerical value of zero 4 Save the file parameters_2 5 Run the following command at the Linux prompt rcvsim parameters 2 foo2 6 Any time after the completion of the previous step execute the following command at the Linux prompt wave r foo2 s 09 17 7 Click on File button with right mouse button and then click Analyze option with left mouse button Change first two waveforms in the Signal List to 9 0 followed by lt RETURN gt Then click on the VCG button Or if Ex 1 has been previously implemented then 1 Execute the following command at the Linux prompt wave r fool s 09 17 2 Click on File button with right mouse button and then click Analyze option with left mouse button
4. Change first two waveforms in the Signal List to 9 0 followed by lt RETURN gt Then click on the VCG button e Execution Output If Ex 1 has not been previously implemented then the following files will be created in the current directory foo2 dat foo2 qrs foo2 hea and parameters 2 0 When the wave executable is implemented the WAVE window in Figure 10 will again initially appear The researcher may then use the arrow buttons at the top of the WAVE display system to scroll through the 300 seconds of generated waveforms When the VCG button is clicked the Gnuplot in Figure 11 will appear illustrating left ventricle pressure volume loops As described in Section 5 1 plotting one waveform against another can be carried out during on line viewing provided that the simulation is paused Moreover any two generated waveforms may be plotted against each other through selection of the first two waveforms in the Signal List Ex 3 e Desired Execution On line display of systemic arterial pressure heart rate and instantaneous lung volume with annotations 29 Gnuplot gt Record temp Signals 90 0 0 20 000 Amplitude mv 120 90 100 Amplitude mv Figure 11 Gnuplot window generated according to Ex 2 Fully controlled fully perturbed fixed rate breathing intact pulsatile heart and circu lation with default parameter values e Required Steps 1 Copy file DIR bin parameters d
5. ventricular pressure volume relationship vary periodically over time time evolution is precisely determined by the end diastolic compliance ed the end systolic es compliance and the heart rate F and are responsible for driving the flow of blood The four ideal diodes represent the ventricular inflow and outflow valves and ensure uni directional blood flow Finally the reference pressure is set to intrathoracic th pressure for the ventricular and pulmonary compartments Figure 2 illustrates the electrical circuit analog of the lumped parameter model of the human heart lung unit preparation The input pressure to the heart lung unit here is defined to be the q S PO Rp q Py t Pura t Ra Pa Figure 3 Electrical circuit analog of the human systemic circulation preparation designed for measuring venous return curves Each box encompassing a circuit element denotes a nonlinear element node labelled P t the location of where the right atrium would be if it were explicitly in cluded in the model Cardiac function curves may be obtained from this preparation by varying the independent voltage sources P and P and time averaging the resulting t and Pera t Figure 3 illustrates the electrical circuit analog of the lumped parameter model of the human systemic circulation preparation Venous return curves may be measured from this preparation b
6. 2 would not be adequate because contracting atrial compartments are not ex plicitly included In such cases the researcher may utilize the RCVSIM source code as a basis for facilitating the construction of a model which can address his research objective An outline of the major steps necessary for the researcher to create different lumped parameter pulsatile heart and circulation models and add new bandlimited regulatory systems e g arterial chemoreflex and resting physiologic perturbations e g central oscillator is provided below Note that additional steps may also be necessary depending upon the particular extension e Creating lumped parameter models of the pulsatile heart and circulation 1 Name the new lumped parameter model preparation and assign a unique number to it This number will be used in conditional statements which must be added to the code in order to distinguish the desired preparation to be executed from the other possible preparations see for example the rk4 m source code 2 Extend the MATLAB parameter vector th to include any additional necessary param eters Add the new parameters in the correct format to the parameter file see Sec tion 5 2 Expand the function read_param m so that it can read these new parameters If the researcher would like to implement the new preparation in the MATLAB envi ronment the function header_def m must also be altered accordingly see Appendix A 3 Create a functio
7. also be possible to compile the source code to create binaries that may be executed on Unix platforms e g Solaris SunOS Note that MATLAB is required for compiling the source code RCVSIM has been previously employed in cardiovas cular research for the development and evaluation of system identification methods aimed at the dynamical characterization of autonomic regulatory mechanisms 4 8 This document specifically explains how to install and use the RCVSIM software and describes the open source code and each of its functions so that RCVSIM may be easily extended and modi fied by the researcher to achieve his desired research objective In Section 2 a brief description of the components and parameters of the human cardiovascular model is given A detailed descrip tion may be found in 4 7 In Section 3 a description of the source code and an explanation of how to alter it are provided In Section 4 detailed instructions on software installation and com pilation are outlined In Section 5 instructions on software execution including many examples are given Finally in Section 6 an example illustrating how the software may be utilized in car diovascular research is provided Note that if the researcher is interested in executing the software but not editing it then he may skip Section 3 without loss of continuity 2 Human Cardiovascular Model The human cardiovascular model upon which RCVSIM is based includes three major com
8. an unstressed volume between the venous and ventricular compartments in Figure 1 The atrial and ven tricular compliances at a desired time step are respectively computed by the functions var_vcap m and var_acap m The initial pressures volumes and flow rates of the prepa ration are computed with the function a_init_cond m and the derivative of the pressures at a desired time step is determined with the function a_eval_deriv m e Resting physiologic perturbations Respiratory activity In addition to fixed rate breathing and random interval breathing with varying tidal volumes Qu t may also be represented as a step or impulse of desired amplitude or area Ofrs and at a desired time Qfrt as well as at random intervals with a constant tidal volume These breathing patterns are generated with the function resp_act m Autoregulation of local vascular beds In addition to bandlimited white noise autoreg ulation of local vascular beds may also be represented as bandlimited f noise or a sinusoid of desired amplitude ar and frequency fr The former representation is generated with the functions bl _filt m and oneoverf filt m Central oscillator A central oscillator is represented as an exogenous sinusoidal dis turbance to P of desired amplitude ap and frequency fp Non baroreflex mediated fluctuations in Q t Fluctuations in Q t not due to the baroreflexes are represented as a white disturbance of desi
9. as the new flag name in the correct format to the parameter file see Section 5 2 Expand the function read_param m so that it can read these new parameters and flag name If the researcher would like to implement the new model in the MATLAB environment the function header _def m must also be altered accordingly see Appendix A 3 Initialize the necessary variables at the beginning of simulate m Create a function to compute the mandated change to the adjustable parameter Call this function every 0 0625 s If this function requires a simulated waveform as input then this waveform must be averaged over the previous 0 25 s every 0 0625 s prior to the function call If a parameter other than F t Ra t Q t and Cf t is adjusted then the following steps must be undertaken a Pre allocate additional memory for the adjustable parameter matrix ap in simu late m b Expand the thc vector in simulate m to include the new parameter to be adjusted c Linearly interpolate the newly adjustable parameter d Assign the mandated adjustment to the ap matrix in simulate m e Expand the ap matrix to be written in MIT format in simulate m and rcvsim m f Adjust the parameter update code in simulate m accordingly g Extend code for generating the MIT format header file in rcvsim m to include the newly adjustable parameter Add the new function to the make files make m and makem m and recompile the code 4 Software Ins
10. compromised 5 3 2 On line Parameter Updating All of the parameter assignments in the working parameter file may be updated as waveforms are being calculated and displayed on line except those labelled with Any updates to these parameters will be ignored As soon as any parameter not labelled with is updated in the working parameter file the file is saved with a new name in order to document fully the simulation see Section 5 1 Some caveats to on line parameter updating are provided below Since none of the display parameters are labelled with a they are permitted to be updated on line Thus the researcher may for example change the waveforms that he is currently viewing without having to rerun rcvsim However when the working parameter file is updated only through the display parameters the update will not be documented to file Updates to the working parameter file are also not documented when the particular update is not relevant to the status of the current simulation For example an update to the Cls parameter 24 is relevant when the intact circulation and heart lung unit preparations are being implemented Thus in this case the update will be documented to file However when the systemic circulation preparation is being executed an update to the Cls parameter is irrelevant see Figure 3 and is thus not documented to file When implementing the heart lung unit the Pv and Pa parameters may be updated on line
11. flag indicating whether the contents of the annotations file which include the times of onset of ventricular contractions and parameter updates will be viewed on line with the waveforms selected by the waveform parame ter Note that if the waveform parameter is set to the numerical value of 1 then the contents of the annotations file will not be displayed on line regardless of the value assigned to the annotations parameter The rcvsim executable file implements on line viewing by periodically updating the WAVE display with the most recently computed window of waveforms The time duration of the window and the update time period both simulation times may be respectively set to desired values with the window and step parameters For optimal on line viewing the window parameter should be set equal to the time duration displayed by WAVE This latter time duration is set by the physical size of the WAVE window as well as the Time scale variable which is essentially a calibration factor mapping this physical size to time duration The Time scale variable may be altered by clicking the VIEW option on the WAVE menu bar The step parameter should be chosen to be sufficiently small such that the displayed waveforms appear to scroll continuously through the WAVE window However if the step parameter is chosen to be too small then the actual time required to update the display of the simulated data may not be sufficient and the quality of viewing may thus be
12. for for time in which this file is created During on line viewing Press p and RETURN at standard input to pause Once paused the following actions may be carried out scrolling backwards with arrow buttons plotting waveforms against each other by clicking on File with the right mouse then Analyze and then VCG the first two waveforms in Signal List will be plotted against each other update parameters in parameterfile and save parameterfile Press r and RETURN at standard input to resume Crmukkamallcusim srcl J Figure 8 Results of executing the rcvsim help option at the Linux prompt 21 5 2 Parameter File The parameter file DIR parameters def see Figure 9 assigns the desired numerical values to all of the parameters characterizing the human cardiovascular model and its execution The syn tax for parameter assignment must be precisely as written within the following squiggly brackets parameter numerical_value Otherwise the parameters will not be read in properly The pa rameter file also includes definitions of each of the parameters and default or nominal parameter values Each line containing these definitions and default values as well as any other comments must be preceded by a Parameter assignments should never be preceded by a else they will not be read in properly Each of the parameters in the file may be updated in the midst of a simulation period with the exception of those labelled with Any u
13. in the file In this way multiple cardiac output and venous return curves can be overlayed on the same axes The mPra x axis formats corresponding to numerical values of 0 and 1 will display either cardiac function or venous return curves The mPa x axis formats corresponding to numerical values of 2 and 3 will display average cardiac output as a function of average systemic arterial pressure and is thus applicable only to the heart lung unit preparation Whether cardiac function and venous return curves are to be viewed on line or off line the simulation time is determined by the time parameter under integration and sampling parameters or the time it takes to complete the calculation of the entire curve which ever is less Hence the time parameter should always be set to a value that is greater than the time it takes to calculate the entire curve 1000 seconds is usually more than enough In order to generate venous return curves the Crds parameter under pulsatile heart and circula tion parameters must be properly selected This parameter determines the increments in which the Crd parameter is stepped from the value assigned to the Crs parameter to 60 ml mmHg Hence this parameter determines the number of points to be calculated on the venous return curve For example if this parameter is set to five and all other parameters are also set to their default values then 12 points on the venous return curve will be calculated If the Crds paramete
14. open source software provided by PhysioNet Type plot2d h at the Linux prompt for help e ww 2 Determine model parameter values which permit the model and averaged experimental heart rate power spectra to match a Copy file DIR bin parameters def to the current directory with the new file name pa rameters T 49 b Open the file parameters_r with any text editor e g emacs c Re assign the following parameters waveform 1 baro 3 dncm 1 breathing 1 dra 1 df 1 Tr 4 and Qt 430 Since accompanying experimental respiratory data is not available the last parameter is arbitrarily set such that the alveolar ventilation rate is 70 ml s d Save the file parameters_r e Execute the following commands at the Linux prompt rcvsim parameters _r foor tach r foor a qrs f gt hrsim memse f 2 Z o 15 hrsim gt phrsim plot2d phrsim 0 1 f If this plot matches the experimental plot above then the research objective has been achieved Otherwise re assign the following parameters bgain again pgain stdwr and stdwf and repeat the steps above beginning with Step d Note that these five parameters have been identified based on a priori knowledge of the physiologic differ ences between supine and standing postures When the values assigned to the parameters of Step f are set as follows bgain 0 5 again 0 5 pgain 1 stdwr 0 04 and stdwf 0 175 the averaged experimental and model supine po
15. the entire integration period from the parameter values and the times of commencement of each respiratory cycle ilv_dec m decimates Qu t to a sampling period equal to 0 0625 s This decimated wave form is convolved with the filter created by dncm_filt m see below in order to establish the changes in F t mandated by the direct neural coupling mechanism dncm_filt m generates a filter which characterizes the direct neural coupling mechanism be tween Qu t and F t bl_filt m generates a lowpass filter with a narrow transition band truncated sinc function of unit area and desired cutoff frequency which is utilized to bandlimit the exogenous distur bance to Ra oneoverf filt m generates a filter with a 1 f P magnitude squared frequency response over a desired frequency range in decades and at a desired sampling period see below 13 e ans filt m creates a filter which is a linear combination of s t and p t This filter is con volved with the filter generated by oneoverf filt m and then white noise in order to create the exogenous disturbance to F t e abreflex m computes the parameter adjustments mandated by the arterial baroreflex system based on the current setpoint and static gain values e cpreflex m computes the parameter adjustments mandated by the cardiopulmonary baroreflex system based on the current setpoint and static gain values e param_change m determines whether the parameter updates are relevant to the
16. volume Q ml current to blood flow rate q ml s and voltage to pressure P mmHg The model consists of six compartments which represent the left and right ventricles l r systemic arteries and veins a v and pulmonary arteries and veins pa pu Each compartment consists of a conduit for viscous blood flow with resistance R and a volume storage element with compliance C and unstressed pa pv pa pv al G gt Ka w Cro Ci t ad Pra 8 Pa t mF e Figure 2 Electrical circuit analog of the human heart lung unit preparation designed for measuring cardiac function curves Each box encompassing a circuit element denotes a nonlinear element volume Q Two of the resistances and two of the compliances are nonlinear The systemic venous resistance is represented by a Starling resistor with chamber pressure set to atmospheric pressure while the pulmonary arterial resistance is represented by an infinite number of parallel Starling resistors with chamber pressure equal to alveolar alv pressure arranged vertically one on top of the other The pressure volume relationships of the left and right ventricles consist of an essentially linear regime characterized by compliance and unstressed volume a diastolic volume limit Q and a systolic pressure limit P The compliances of the linear regime of the
17. with increasing P t The initial pressures volumes and flow rates of the preparation are computed with the function nac_init_cond m and the derivative of the pressures at a desired time step is determined with the function nac_eval_deriv m Intact circulatory preparation with third order systemic arteries and nonlinear large elastic arterial compliance This preparation is a combination of the previous two preparations with a nonlinear Ce and linear Cm The initial pressured volumes and flow rates of the preparation are computed with the function third_nac_init_cond m and the derivative of the pressures at a desired time step is determined with the function third nac_eval_deriv m Intact circulatory preparation with an arterial pressure reservoir preparation The electrical circuit analog of this preparation may be visualized by replacing Cg in Fig ure 1 with a DC voltage source P This preparation may be utilized to understand 52 hemodynamics while P t is held constant The initial pressures volumes and flow rates of the preparation are computed with the function apr_init_cond m and the deriva tive of the pressures at a desired time step is determined with the function apr_eval deriv m Intact circulatory preparation with contracting atria The electrical circuit analog of this preparation may be visualized by inserting right atrial ra and left atrial la com partments linear resistor and linear variable capacitor with
18. 1 Ex 6 e Desired Execution On line display of systemic arterial pressure intrathoracic pressure and instantaneous lung volume with annotations Uncontrolled intact pulsatile heart and circulation initially with default parameter val ues perturbed by only fixed rate breathing First an on line reduction in lung compliance by a factor of two Then an on line 500 ml step increase in the functional reserve volume of the lungs e Required Steps 33 6 4 Record temp qrs File gt View Edit Properties 7 lt Search lt lt lt Find gt gt gt Search gt Help Quit N N N parameters 5 f 3 49 4 09 Grid intervals 0 2 sec x 0 5 mV Figure 13 WAVE window generated according to Ex 5 34 nA A 0 N Copy file DIR bin parameters def to the current directory with the new file name pa rameters_6 Open the file parameters_6 with any text editor e g emacs Re assign the following parameters waveform 1 6 15 and breathing 1 Save the file parameters_6 Run the following command at the Linux prompt rcvsim parameters_6 foo6 Some time in the midst of the simulation type p followed by lt RETURN gt at stan dard input Re assign the the following parameter Clu 126 25 8 Save the file parameters_6 11 12 13 Type Y followed by lt RETURN gt at standard input 10 At a subsequent time during the simulation type p followed b
19. 7 S arctan 3 dr ap 1 where ap may represent any of the four adjustable parameters the arctan function which is parametrized by the constant S imposes arterial baroreflex saturation p t and s t are unit area effector mechanisms which respectively represent the fast parasympathetic limb of the ANS and the slower sympathetic limb both a and 6 sympathetic sublimbs see Figure 5 and Gp and Gs reflect the respective static gain values of the effector mechanisms Note that in order to map F t to the times of onset of ventricular contraction which amounts to re initiating the variable ventric ular compliance time evolution an integrate and fire model of the sinoatrial node is incorporated in the model The cardiopulmonary baroreflex arc is also implemented according to a feedback diagram anal ogous to Figure 4 However the sensed pressure here is defined to be the effective right atrial transmural pressure P t Pera t Pin t of the pulsatile heart and circulation model The direct neural coupling mechanism between respiration and heart rate is characterized by 7 a b 0 9 0 97 0 8 0 87 0 7 0 7 0 6 0 67 20 51 S 0 51 0 4t 0 4 0 3 0 3 0 2 0 21 0 1t 0 1 10 20 30 10 20 30 Time s Time s Figure 5 Unit area effector mechanisms representing a the fast parasympathetic limb p t and b the slower sympathetic limb s t These effector mechanisms characterize t
20. A Cardiovascular Simulator for Research User s Manual and Software Guide Ramakrishna Mukkamala Harvard MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA 02139 February 3 2004 Contents 1 Introduction 2 Human Cardiovascular Model 2 1 Pulsatile Heart and Circulation 400 a ice ae ee Oo EE ee a Oe ee 2 2 Short Term Regulatory System 204 4 sha oe GS aS ele Glee eee ele 2 3 Resting Physiologic Perturbations e e o 3 Source Code 3 1 Flowchart and Functions oaoa aaa a 3 2 Modifications and Extensions 4 Software Installation and Compilation Ae Installation at A ARA Re Boe Re Bo ee te BE 4 2 Compilation e 2 eee ee Ok EO Oke Oke Cee ee eee Se BGS 5 Software Execution o AAA A sl aca Arete aie 3 2 Parameter FIE Age o A A LA E RO E RA 5 3 Viewing Waveforms alae a a ew ee ee a ee A 5 3 1 Setting Display Parameters lena e Soe a at 5 3 2 On line Parameter Updating a RS 5 4 Viewing Cardiac Function and Venous Return Curves 5 5 Viewing Examples iO RRA AAA AA ty AAA 6 A Research Example A Other Models 10 15 16 17 19 1 Introduction Computational modeling and simulation studies can facilitate the advancement of cardiovascular research by complementing experimental studies Through computational studies the researcher may formulate hypotheses which may be subsequently tested through experimental studies or
21. WFDB software package version 10 1 6 e doc This sub directory includes this very document in HTML PDF manual pdf PostScript manual ps and LaTeX source manual tex formats 3 Login as root 17 4 Download and install the WFDB software package and the WAVE display system if this has not already been done See the following web page for instructions http www physionet org physiotools wfdb linux quick start shtml If the researcher is running Linux Redhat 6 2 or higher then 5 Type the following command in the DIR directory install The results of Step 5 are as follows e The WFDB Software Package version 10 1 6 in the D R ib directory will be installed if an older version is currently installed e The libc5 libraries and old ld so dynamic linker RPMs in the DIR lib directory will also be installed Note that recent Linux systems use libc and a new linker but will not be affected by the installation of the older libraries and linker e An rcvsim executable shell script will be placed in the D R bin directory This script sets the library and WFDB paths for its subsequent execution of the binary DIR src rcvsim and is linked to the directory usr local bin which should already be in the researcher s path e The MATLAB binary executable simulate mexlx will be linked to a directory in the MAT LAB path if MATLAB is present Or if the researcher is running Linux Redhat 6 1 or lower or any other Linux distr
22. ameter under the status parameters a numerical value of 1 or 2 Provided that this has been done then the numerics parameter under the display parameters determines whether the cardiac function venous return curve is to be viewed on line If the numerics param eter is assigned the numerical value of 1 then the curve will not be displayed as soon as it is 25 calculated but may be subsequently viewed off line If the numerics parameter is set to a numeri cal value between 0 and 3 inclusive which correspond to different plotting formats see Figure 9 then the cardiac function venous return curve will be automatically displayed immediately follow ing the completion of the simulation The different plotting formats can be best understood by recognizing that the on line display of the curves is specifically implemented by writing gnuplot commands to a file in the mp directory and executing these commands through a function call to gnuplot The single plot per window formats corresponding to numerical values of O and 2 will delete this file if it exists write a new file to the tmp directory and thus display only the cardiac function venous return curve of the current simulation The multiple plots per window formats corresponding to numerical values of 1 and 3 will add plotting instructions to the existing file in the tmp directory and thus display the curve of the current simulation as well as all other curves that are instructed to be displayed
23. appropriate status parameter should be deactivated for the purposes of increasing execution speed Note that the pulsatile heart and circulation parameters may be applicable to the intact circulation heart lung unit and or systemic circulation preparations and are labelled accordingly 5 3 Viewing Waveforms Provided that the display parameters are properly set the researcher may view the simulated wave forms and update the parameter values on line by running the rcvsim executable which will make repeated function calls to the WAVE display system Alternatively the waveforms which are recorded to MIT format files may be viewed at any time after completion of the simulation off line viewing by directly running the wave executable file at the Linux prompt An explanation on how to set the display parameters and caveats to on line parameter updating are provided below See also Examples 1 7 in Section 5 5 which illustrate how to view waveforms both on line and off line 22 Buffers Files Tools Edit Search Mule Help Parameters characterizing the cardiovascular simulator and its execution z 2 The following parameter assignment format must be maintained Z parameter numerical _value z Parameters labelled cannot be adjusted on line any changes to these Z parameters will simply be ignored Integration and sampling parameters Z Integration Sampling frequency of generated signals Def 125 Hz Z WARNING smaller sampl
24. are computed with the function init_cond m and the derivative of the pressures at a desired time step is determined with the function eval_deriv m Intact circulatory preparation with third order systemic arteries The electrical circuit analog of this preparation may be visualized by replacing the capacitor Ca in Figure 1 with two grounded capacitors connected via an inductor The capacitor proximal to the left ventricle compartment represents the large elastic e arteries the other capacitor represents the small muscular m arteries and the inductor L accounts for the in ertial effects of blood flow between the two lumped arteries This third order model of the systemic arteries was previously presented by Clark 2 The P t waveform may be considered as a first order approximation of a peripheral arterial blood pres sure waveform The initial pressures volumes and flow rates of the preparation are computed with the function third_init_cond m and the derivative of the pressures at a desired time step is determined with the function third _eval_deriv m Intact circulatory preparation with nonlinear systemic arterial compliance The elec trical circuit analog of this preparation is given by Figure 1 with a box encompassing C a to denote its nonlinearity This nonlinear element is characterized by the curvature K differential compliance Ca and volume Qnac all at PP Provided that K lt 0 the differential compliance decreases
25. calls upon many MATLAB and C functions each of which are briefly described below e intact_init_cond m computes the initial pressures volumes and flow rates of the intact pul satile heart and circulation model from the desired parameter values The initial values are determined from the solution of a linear system of equations which are derived from the application of steady state conservation laws to a linearized version of the model e hlu_init_cond m computes the initial pressures volumes and flow rates of the heart lung unit preparation model from the desired parameter values The initial values are determined from the solution of a linear system of equations which are derived from the application of steady state conservation laws to a linearized version of the model e sc_init_cond m computes the initial pressures volumes and flow rates of the systemic circu lation preparation model from the desired parameter values The initial values are determined from the solution of a linear system of equations which are derived from the application of steady state conservation laws to a linearized version of the model 12 rk4 m computes the pressures of the pulsatile heart and circulation any preparation at the current time step from the pressures of the previous time step the current values of the parameters respiratory related waveforms and time surpassed in the current cardiac cycle according to fourth order Runge Kutta integration i
26. ctory with the new file name pa rameters 2 Open the file parameters_5 with any text editor e g emacs 3 Re assign the following parameter waveform 1 10 Make sure all of the status param eters are assigned the numerical value of zero 4 Save the file parameters_5 5 Run the following command at the Linux prompt rcvsim parameters _5 foo5 6 Some time in the midst of the simulation type p followed by lt RETURN gt at stan dard input 7 Re assign the the following parameter Ca 0 8 8 Save the file parameters_5 9 Type tr followed by lt RETURN gt at standard input e Execution Output A WAVE window will appear and will automatically scroll through the simulated data with annotations The automatic scrolling will stop once Step 6 is executed At this point the researcher may scroll backwards with the the arrow buttons at the top of the WAVE display system After Steps 7 9 are executed automatic scrolling will resume until a total of 300 seconds of data have been calculated Figure 13 illustrates the WAVE window during the time of reduction in systemic arterial compliance Note that this reduction is annotated with the name of the saved parameter file Also note how systemic arterial volume is conserved through the instantaneous change in systemic arterial pressure The following files will be created in the current directory foo5 dat foo5 qrs foo5 hea parameters_5 0 and parameters_5
27. e code was written predominantly in the MATLAB language version 5 3 1 R11 1 and includes some C language necessary for on line viewing and parameter updating The source code may be compiled using the MATLAB compiler version 1 2 with the libc5 devel opment environment at the MATLAB prompt see Section 4 2 Note that compilation permits software execution at the Linux prompt and greatly improves execution speed The source code not only consists of code to implement the models described in Section 2 but also includes code to implement other models These latter models have been minimally tested and documented and may only be executed in the MATLAB environment A description of the code for implementing the models of Section 2 and an explanation of how this code may be modified or extended to im plement arbitrary lumped parameter cardiovascular models are provided below See Appendix A for a brief description of the other models and the source code for executing them 3 1 Flowchart and Functions The source code is based on the MATLAB function simulate m The input arguments to simu late m include the desired parameter values characterizing the human cardiovascular model and its execution while the outputs are the simulated data all pressures P t volumes Q t flow rates q t ventricular elastances E t adjustable parameters ap t cardiac function venous return curves numerics and ventricular contraction times qrs This functio
28. ectory and basic execution and compilation instructions e INSTALL This text file explains how to install uninstall the RCVSIM software on Linux or other platforms in which the WAVE display system is fully supported e install This shell executable script automates some or all of the installation process e uninstall This shell executable script is designed to undo what was done by the install script e src This sub directory includes all the source code described in Section 3 1 and Appendix A as well as two other C files check_redhat c and check_wfdb c which are required by the install and uninstall shell scripts The Linux and MATLAB pre compiled binaries revsim and simulate mexlx are also stored here e bin This sub directory includes parameter files parameters def and header_def m see Sec tion 5 2 and Appendix A which are respectively required for execution at the Linux and MATLAB prompts a wfdbcal file responsible for scaling the simulated waveforms displayed by WAVE and the two binaries check_redhat and check_wfdb e lib This sub directory consists of libraries which are required for executing the binaries These libraries include the dynamic MATLAB libraries which permit software execution in the absence of MATLAB two RPMs containing libc5 libraries and an old ld so dynamic linker part of the Redhat 6 2 distribution which are necessary for dynamically linking the MATLAB libraries and a tar file consisting of the
29. ef to the current directory with the new file name pa rameters_3 2 Open the file parameters_3 with any text editor e g emacs 3 Re assign the following parameters waveform 1 15 26 baro 3 dncm 1 breathing 1 dra 1 and df 1 4 Save the file parameters_3 5 Execute the following command at the Linux prompt rcvsim parameters_3 foo3 e Execution Output A WAVE window will appear and will automatically scroll through the simulated data with annotations Figure 12 illustrates the window after one minute of data has been calculated This process will terminate once 300 seconds of data have been simulated The following files will be created in the current directory foo3 dat foo3 qrs foo3 hea and parameters_3 0 Ex 4 30 6 4 Record temp qrs File v View Edit Properties 7 lt Search lt lt lt Find gt gt gt Search gt Help Quit Grid intervals 0 2 sec x 0 5 mV Figure 12 WAVE window generated according to Ex 3 and Ex 4 31 e Desired Execution Off line display of systemic arterial pressure heart rate and instantaneous lung volume with annotations Fully controlled fully perturbed fixed rate breathing intact pulsatile heart and circu lation with default parameter values e Required Steps 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters 4 2 Open the file parameters_4 with any text editor e g e
30. ent directory The rcvsim executable also permits the simulated waveforms as a function of time to be viewed as they are being calculated on line viewing through the WAVE display system The sim ulation may be paused during on line viewing by simply entering p followed by lt RETURN gt at the standard input Once the simulation is paused any and all of the following three actions may be carried out 1 All the data that have been generated up to the time of the pause may be scrolled through with the arrow buttons at the top of the WAVE display system 2 Plots of one generated waveform against another may be displayed by clicking the File button at the top of the WAVE display system with the right mouse button and then clicking on the Analyze option followed by the VCG button both with the left mouse button The first two waveforms appearing in the Signal List first waveform is plotted on x axis and the second waveform on y axis which may be adjusted as desired will then be plotted against each other via Gnuplot 3 The working parameter file may be updated and saved The simulation may be resumed with the updated pa rameter values by simply entering Y followed by lt RETURN gt at the standard input Note that plots of one waveform versus another will not be automatically updated upon resuming the simu lation However these plots may be manually updated by subsequently pausing the simulation and regenerating the plot as desc
31. ers_12 0 Ex 13 e Desired Execution Off line display of the curve of average cardiac output as a function of average systemic arterial pressure generated from Ex 12 e Required Steps 1 Change directory to that which contains the simulated data of Ex 12 2 Run gnuplot at the Linux prompt 3 At the Gnuplot prompt enter the following commands set tics out set xlabel mPa mmHg set ylabel mq l min plot fool2 txt using 3 2 notitle with lines e Execution Output The Gnuplot window of Figure 21 will again appear 6 A Research Example The human cardiovascular model upon which RCVSIM is based was originally constructed in or der to advance research in the general area of beat to beat hemodynamic variability 4 8 The RCVSIM software enhances the potential of the original human cardiovascular model in facilitating cardiovascular research by making the model more user friendly and compatible with the open source software provided by PhysioNet By further disseminating RCVSIM to the cardiovascular research community through PhysioNet researchers may conveniently utilize the computational model to complement their studies with the experimental data sets available on PhysioNet For example RCVSIM has been previously utilized to develop an algorithm for monitoring systemic arterial resistance from only a peripheral arterial pressure waveforms which was subsequently val idated with data from the MIMIC databa
32. he dynamical properties of the block labelled ANS in Figure 4 a linear time invariant impulse response which maps fluctuations in instantaneous lung volume Q t see Section 2 3 to fluctuations in F t The impulse response is defined here by a linear combination of s t and p t each of which are advanced in time by 1 5 s in order to account for the noncausality of this mechanism 6 9 2 3 Resting Physiologic Perturbations Respiratory activity which may either be at fixed rate or random intervals 1 is modeled in terms of Qu t Fixed rate Qu t is represented by a pure sinusoid which is characterized by tidal volume Q and respiratory period T as well as a DC offset representing the functional reserve volume of the lungs Qr Each respiratory cycle of random interval Qu t is also represented by one period of a sinusoid with the DC offset Q fr However the period is not constant here but rather determined based on the outcome of a probability experiment which ranges from one to 15 seconds with a mean of five seconds and the tidal volume is set such that the instantaneous alveolar ventilation rate which considers the dead space in the airways Quas is identical to that of fixed rate breathing In order to account for the mechanical effects of Qu t on Pin t and Pay t the simple model of ventilation illustrated in Figure 6 in terms of its electrical circuit analog is also incorporated in the model The electrical comp
33. he settings below Z Status of heart and circulation 20 intact circulation g 1 heart lung unit 2 systemic circulation preparation 0 Figure 9 The DIR parameters def file which contains the parameter values characterizing the human cardiovascular model of Section 2 and its execution 23 5 3 1 Setting Display Parameters The waveform parameter under the display parameters in the working parameter file determines whether the simulated waveforms are to be viewed on line If the waveform parameter is assigned the numerical value of 1 then the waveforms are not displayed as they are being calculated but may be subsequently viewed and analyzed off line The researcher may choose this option if for example the data required for analysis are very time consuming to generate e g Monte Carlo simulations If the waveform parameter is assigned one or more numerical values between O and 28 inclusive with a single space inserted between each assigned numerical value then the wave forms corresponding to those numerical values see the DIR pararmeters def file Figure 9 or the generated file with extension hea for mapping key between waveforms and numerical values will be displayed as they are being calculated For example in Figure 9 the waveform parameter is set such that left ventricle and systemic arterial pressures will be displayed on line Note that the annotations parameter beneath the waveform parameter is simply a
34. ibution e g Suse Debian then 5a Acquire and install the necessary libc5 libraries and old dynamic linker if they are not cur rently present on the system 5b Type the following command in the DIR directory install For RPM based distributions e g Mandrake the software required for Step 5a may be found on rpmfind net as was the case for the RPMs provided in the directory DIR lib Please see the following web pages http www rpmfind net linux rpm2html search php query ld so http www rpmfind net linux rpm2html search php query libc Note that the results of Step 5b differ from those of Step 5 in that the RPMs of DIR lib will not be installed 6 To undo the install script type the following command in the DIR directory uninstall This will undo everything done by install except the removal of the WFDB Software Package version 10 1 6 if it were installed This software can be removed manually read INSTALL file in the tar file wfdb 10 1 6 tar gz which is located in the DIR lib directory 18 4 2 Compilation If the researcher is running Linux and wishes to modify extend the RCVSIM source code or if the researcher would like to run the RCVSIM software on another platform in which WAVE is fully supported then compilation is necessary The steps required to compile the source code are are as follows 1 Acquire and install MATLAB with the MATLAB compiler version 1 2 if they are not currently avai
35. ing frequency leads to greater integration errors Fs 125 Total integration time s Z Set time 1000 for cardiac function venous return curves Simulator will stop integration as soon as the computation Z of the curves is complete time 300 2 Display parameters Waveforms to be viewed Simulated waveforms and corresponding numerical values 21P101 Pa1 Pu21Pr3 Ppa4 Pps I 2 Pth 6 Palv 7 Pra 8 1 Q19 1 Qa 10 Ov 11 21 Or 12 Qpa 13 Opv 14 Olu 15 qpu 16 ql 17 Xx qa 18 qv 19 gr 20 qpa 21 Cls 22 Crs 23 2 Qvo 24 Ra 25 F 26 El 27 Er 28 1 Place single space between each waveform number 2 For no waveforms write waveform 1 waveform 1 Z Annotation to be viewed Z0 no 1 yes annotations 1 Time duration of window of displayed waveforms lt s 2 For best viewing set window WAVE time window See View option on WAVE menu bar for adjustment Z of WAYE time window windows 20 2 Time period between waveform display updates s Z WARNING smaller step values lead to display errors step 2 Cardiac function venous return curve plotting format Z 1 no plot single plot per window x axis mPra multiple plots per window x axis mPra single plot per window x axis mPa multiple plots per windows x axist mPa Note 2 and 3 are only applicable to heart lung unit numerics 0 2 Status parameters 2 These parameters override any of t
36. ion curves are recorded over the beat preceding the step variation 10 Parameters Outputfile Declaring and Initializing Variables t 0 tT Numerical Integration for Calculating P t Adjusting Parameters by Regulation Perturbations Establish qrs via Integrate and Fire Heart Lung Unit or Systemic Circulation Calculating Q t and Storing E t and ap t Yes Correcting Q t t Intact Circulation by Adjusting O Conserving Q t and Documenting Updates Varying P P C and Averaging Pira t q y t t t T Updated Parameters Calculating q t i R Writing Waveforms Line Vi SERIE VE to MIT Format Files Outputfile hea No Outputfile dat Outputfile qrs Displaying Waveforms Y P t Q t q t E t ap t qrs numerics Figure 7 Flowchart of the MATLAB function simulate m 11 e Calculating Q t and Storing E t and ap t The blood volumes of each compartment of the desired model of the pulsatile heart and circulation are computed at the current time step from the pressures at the current time step and the values of the ventricular elastances and adjustable parameters at the current time step are stored into their pre allocated memory slots e Intact Circulation 4 Correcting Qto t by Adjusting P t Total blood volume of the intact pulsatile heart and circulation at the curren
37. isplay of a cardiac output curve On line display of systemic arterial and venous pressure and left ventricle flow rate Uncontrolled unperturbed heart lung unit preparation with default parameter values e Required Steps 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters_8 2 Open the file parameters_8 with any text editor e g emacs 3 Re assign the following parameters time 1000 waveform I 2 17 preparation 1 Pas 1000 and Pvs 2 4 Save the file parameters_8 5 Run the following command at the Linux prompt rcvsim parameters _ amp foo8 e Execution Output A WAVE window will appear and will automatically scroll through the simulated data as they are being calculated until the entire cardiac output curve has been measured Figure 17 illustrates the WAVE window at the end of the simulation As is always the case with viewing waveforms on line the parameter values may be updated prior to simulation termination if desired Then the Gnuplot window of Figure 18 will appear immediately following the calcu lation of the entire cardiac output curve The following files will be created in the current directory foo8 dat foo8 qrs foo8 hea foo8s txt and parameters 8 0 Ex 9 e Desired Execution On line display of a venous return curve Uncontrolled unperturbed systemic circulation preparation with default parameter values e Required Step
38. lable 2 Establish a libc5 development environment See the following web page for detailed instruc tions http www mathworks com support solutions data l 1129 shtml 3 Launch MATLAB from the DIR directory 4 At the MATLAB prompt execute the following commands cd src make makem By implementing these steps in the Linux environment new rcvsim and simulate mexlx binaries will be created in the D R src directory If the RCVSIM software has already been installed then re installation is unnecessary after compilation On platforms other than Linux the above steps must be carried out prior to software installation on platforms other than Linux Additionally the install and uninstall scripts in the DIR directory need to be slightly modified in order to include the different MATLAB binary file extension name that results from compiling on a different platform For example if compilation is achieved on the Solaris platform simulate mexlx in the install and uninstall files must be replace with simulate mexsol as the latter file will be created in the DIR src directory Then the newly compiled software may be installed according to the previous section Note that it is possible to compile the source code with the latest MATLAB compiler version 2 1 However the binaries generated from this compiler are on the order of three magnitudes slower than those generated with the MATLAB compiler version 1 2 Mathworks is currently trying to impro
39. m eters will be adjusted Note that updates to the Crs and Cls parameters will take effect at the start of the subsequent ventricular contraction 5 4 Viewing Cardiac Function and Venous Return Curves Provided that the relevant parameters are properly set the researcher may view cardiac function and venous return curves immediately after they have been calculated on line viewing by running the rcvsim executable which will make a function call to Gnuplot Since the time required for generating a cardiac function or venous return curve is relatively short within a few seconds the on line viewing capability will usually suffice However it is possible that the researcher may also desire to view the curves off line Since the curves are written to file in ASCII multi column format the researcher may view them any time after completion of the simulation by directly executing gnuplot at the Linux prompt A description of how to set the relevant parameters is given below See also Examples 8 13 in Section 5 5 which illustrate how to view the cardiac function and venous return curves both on line and off line Note that this section requires some familiarity with Gnuplot which may be garnered by typing man gnuplot at the Linux prompt In order for the rcvsim executable to generate a cardiac function or venous return curve either the heart lung unit preparation or systemic circulation preparation must be implemented by assign ing the preparation par
40. macs 3 Re assign the following parameters waveform 1 baro 3 dncm 1 breathing 1 dra 1 and df 1 4 Save the file parameters 4 5 Run the following command at the Linux prompt rcvsim parameters 4 foo4 6 Any time after the completion of the previous step execute the following command at the Linux prompt wave r foo4 s 1 15 26 a qrs Or if Ex 3 have been previously implemented then 1 Execute the following command at the Linux prompt wave r foo3 s 1 15 26 a qrs e Execution Output If Ex 3 has not been previously implemented then the following files will be created in the current directory foo4 dat foo4 qrs foo4 hea and parameters 4 0 When the wave executable is implemented a WAVE window will appear The re searcher may then use the arrow buttons at the top of the WAVE display system to scroll through the 300 seconds of generated waveforms with annotations Figure 12 will appear after clicking the forward double arrow button twice or by directly running the wave executable with the following additional argument f 40 Ex 5 e Desired Execution On line display of systemic arterial pressure and volume with annotations Uncontrolled unperturbed intact pulsatile heart and circulation initially with default parameter values On line reduction in systemic arterial compliance by a factor of two 32 e Required Steps 1 Copy file DIR bin parameters def to the current dire
41. n called preparation_init_cond m to generate the initial pressures vol umes and flow rates Call this newly created function at the same point in simulate m as the function call for intact_init_cond m 4 Create a function called preparation_eval_deriv m to calculate the derivative of the pres sure values at a desired time step Call this newly created function from rk4 m analo gous to the function calls for intact_eval_deriv m 5 Add code for calculating volumes and flow rates at the point in simulate m in which these waveforms are computed for the other preparations 6 If necessary pre allocate additional memory for the simulated data in simulate m ex pand matrices to be written in MIT format in simulate m and rcvsim m and extend code for generating the MIT format header file in rcvsim m 7 Adjust parameter update code in simulate m including conserve vol m 8 Add preparation_init_cond m and preparation init cond m to the make files make m and makem m and recompile the code e Adding bandlimited regulatory system resting physiologic perturbation 15 Name the new regulatory system resting physiologic perturbation This name will serve as a flag indicating whether the new addition is to be activated or not The MATLAB vector flag at the start of simulate m should be extended to incorporate this name Extend the MATLAB parameter vector th to include any additional necessary param eters Add the new parameters as well
42. n may also write the simulated data to file with a desired prefix file name also provided as an input argument and display the data as they are being calculated The function is responsible for executing the models described in Section 2 as well as in Appendix A However the flowchart of Figure 7 depicts how the function simulates the data from the desired parameter values characterizing only the models of Section 2 The pertinent details of each block of the flowchart are provided below e Declaring and Initializing Variables t 0 With the desired parameter values provided as function input arguments all variables of the simulation are declared and initialized Mem ory is pre allocated for all of the data to be simulated over their entire integration period in order to increase execution speed with the MATLAB compiler The respiratory related waveforms are pre computed over the entire integration period e Numerical Integration for Calculating P t The pressures of the desired model of the pul satile heart and circulation are calculated at the current time step t T from the pressures at the previous time step by fourth order Runge Kutta integration of the set of ordinary differential equations governing the model T must be set to 0 005 s for reasonable accu racy e Adjusting Parameters by Regulation Perturbations Parameters of the pulsatile heart and circulation are adjusted by the short term regulatory system and resting phy
43. ndow displaying the previous cardiac output curve with a venous return curve followed by a window displaying these two previous curves with another venous return curve which is enhanced and ending with a window displaying each of these three curves and an additional enhanced cardiac output curve see Figure 20 Note the increase in average cardiac output that occurs due to the enhancement of the curves Each of the four windows will appear immediately after the completion of each of the four rcvsim executions Steps 5 8 11 14 The following files will be created in the current directory foo10a dat fool0a qrs foo10a hea foo10a txt foo10b dat foo10b qrs fool 0b hea foo 10b txt foo10c dat fool0c qrs fool0c hea fool0c txt fool0d dat fool0d qrs fool0d hea foo10d txt and parame ters_10 0 Ex 11 e Desired Execution 45 Off line display of the cardiac output and venous return curves generated from Ex 10 e Required Steps 1 Change directory to that which contains the simulated data of Ex 10 2 Run gnuplot at the Linux prompt 3 At the Gnuplot prompt enter the following commands set tics out set xlabel mPra mmHg set ylabel mql mqv l min plot fool0a txt using 1 2 notitle with lines replot foo10b txt using 1 2 notitle with lines replot foo10c txt using 1 2 notitle with lines replot foo10d txt using 1 2 notitle with lines Note that the plot command is similar to
44. ntact_eval_deriv m is called only by rk4 m and computes the derivative of the intact pulsatile heart and circulation pressure values at a desired time step which is necessary for the fourth order Runge Kutta integration hlu_eval_deriv m is called only by rk4 m and computes the derivative of the heart lung unit preparation pressure values at a desired time step which is necessary for the fourth order Runge Kutta integration sc_eval_deriv m is called only by rk4 m and computes the derivative of the systemic circula tion preparation pressure values at a desired time step which is necessary for the fourth order Runge Kutta integration var_cap m is also called by intact_eval_deriv m hlu_eval_deriv m and sc_eval_deriv m and computes a ventricular elastance value as well as its derivative at a desired time step from the current values of Cf Ce the previous cardiac cycle length and the time surpassed in the current cardiac cycle vent_vol m is also called by intact_eval_deriv m hlu_eval_deriv m and sc eval_deriv m and computes the current ventricular blood volume from the current ventricular pressure accord ing to Newton s search method with an initial guess given by the previous ventricular blood volume rand_int_breath m computes the time until the next respiratory cycle commences based on the outcome of an independent probability experiment resp_act m computes the respiratory related waveforms Qu t Pin t sO and Paty t over
45. numerics 0 while the replot command is analogous to numerics 1 e Execution Output Ex 12 A total of four Gnuplot windows will be displayed beginning with a window displaying a single cardiac output curve see Figure 18 then a window displaying the previous cardiac output curve with a venous return curve followed by a window displaying these two previous curves with another venous return curve which is enhanced and ending with a window displaying each of these three curves and an additional enhanced cardiac output curve see Figure 20 e Desired Execution On line display of average cardiac output as a function of average systemic arterial pressure Uncontrolled unperturbed heart lung unit preparation with default parameter values e Required Steps Copy file DIR bin parameters def to the current directory with the new file name pa rameters_12 2 Open the file parameters_12 with any text editor e g emacs 3 Re assign the following parameters time 1000 waveform 1 numerics 2 prepara tion 1 Pas 30 and Pvs 100 Save the file parameters_12 5 Run the following command at the Linux prompt rcvsim parameters_12 foo12 46 e Execution Output The Gnuplot window of Figure 21 will appear immediately following the calculation of the entire curve The following files will be created in the current directory foo12 dat foo12 qrs foo12 hea foo12 txt and paramet
46. onents may be interpreted similarly to those in Figure 1 by considering air here rather than blood Hence the resistor Rair may be thought of as a conduit for airflow between the atmosphere and the lungs while the capacitor may be interpreted as an air volume container representing the lung compartment which is parametrized by an unstressed dQ lu t dt Ro air Pa t Patm fe Cy Pin t Figure 6 Electrical circuit analog of the human ventilatory mechanics model volume Q in addition to Cu The systemic effects of the autoregulation of local vascular beds is represented with an exoge nous disturbance to R t which is defined by a bandlimited Gaussian white noise process This process is created by convolving Gaussian white noise of zero mean and stdwr standard deviation with a lowpass filter truncated unit area sinc function of desired frequency cutoff fco Higher brain center activity impinging on the ANS is modeled with a f exogenous Gaussian disturbance to F t convolved with a filter defined by a linear combination of s t G sympathetic sublimb and p t The f Gaussian disturbance is created by convolving Gaussian white noise of zero mean and stdwf standard deviation with a unit area filter of f magnitude squared frequency response from 1074 Hz to 1 Hz where alpha is set to one Each of these exogenous disturbances are treated as unobservable quantities 3 Source Code The RCVSIM sourc
47. pdate to these parameters will simply be ignored The parameter file consists of integration and sampling parameters display parameters status parameters pulsatile heart and circulation parameters short term regulatory system parameters and resting physiologic perturbation parameters The status parameters are flags which indicate the preparation of the pulsatile heart and circulation to be implemented as well as whether a particular short term regulatory system or resting physiologic perturbation is to be activated or deactivated The status parameters which cannot be adjusted in the midst of a simulation period override any of the other relevant parameters assignments For example if dra is set to zero then the exogenous disturbance to Ra is deactivated and may not be activated during the simulation period regardless of the value assigned to stdwr which establishes the standard deviation of the disturbance to Ra Note that a short term regulatory system or resting physiologic perturbation may also be deacti vated through the parameters that characterize them For example the exogenous disturbance to Ra may be deactivated by setting stdwr to zero In this case the exogenous disturbance to Ra may be subsequently activated during the simulation period by setting stdwr to a value greater than zero However if the researcher knows that a short term regulatory system or resting physio logic perturbation is not required for his simulation then the
48. ponents The first component is a lumped parameter model of the pulsatile heart and circulation which may be implemented as an intact preparation a heart lung unit preparation designed for measuring car diac function curves or a systemic circulation preparation designed for measuring venous return curves The second component is a short term regulatory system model which includes an arterial 3 Ppt Roa Pt R pv i q 0 ps q 0 Cu o Core pl Pa Pa POAR en II UH AR Po cC Cit L q R q 0 q 0 P t Pa t O Pura t Ry Ra C A CIEN C X EURO Figure 1 Electrical circuit analog of the intact human pulsatile heart and circulation Each box encompassing a circuit element denotes a nonlinear element baroreflex system a cardiopulmonary baroreflex system and a direct neural coupling mechanism between respiration and heart rate The final component is a model of resting physiologic perturba tions which includes respiration autoregulation of local vascular beds exogenous disturbance to systemic arterial resistance and higher brain center activity impinging on the autonomic nervous system f exogenous disturbance to heart rate 2 1 Pulsatile Heart and Circulation The lumped parameter model of the intact pulsatile heart and circulation is illustrated in Figure 1 in terms of its electrical circuit analog Here charge is analogous to blood
49. pro vided that they are not being adjusted through the Pvs and Pas parameters respectively Otherwise the on line adjustment of the Pv and Pa parameters will be ignored Similarly when implementing the systemic circulation preparation any update to the Crd parameter will be ignored unless it is not being adjusted through the Crds parameter As described in Section 3 1 the volume in each of the capacitive elements of the pulsatile heart and circulation any preparation is always conserved through a pressure adjustment The only exception to this rule is naturally when the researcher desires to adjust total blood volume through the Otot parameter which is only applicable to the intact pulsatile heart and circulation preparation In this case the volume is added to or subtracted from the systemic venous volume and the systemic venous pressure is adjusted accordingly The instantaneous lung volume waveform may only be altered by updating the following pa rameters Tr Qt Ofrs and Ods If parameters of the ventilatory model in Figure 6 are updated which includes the Pvc parameter the value of intrathoracic pressure at the functional reserve volume of the lungs will be adjusted instantaneously in order to preclude any change to instanta neous lung volume Finally when updating the adjustable parameters of the pulsatile heart and circulation through the F Ra Qvo Crs and Cls parameters the current values and the setpoint values of these para
50. r is set to a value greater than 60 Crs then the Crd parameter will be held constant throughout the simulation and only one point on the venous return curve will be generated In order to generate cardiac function curves the Pvs and Pas parameters under pulsatile heart and circulation parameters must be properly selected Analogous to the Crds parameter these pa rameters indicate the increments in which the Pv and Pa parameters are stepped If the simulation of a cardiac output curve is desired the Pa parameter should be held constant by setting the Pas parameter to a very large value 1000 mmHg will usually be more than sufficient and the Pvs pa rameter should be set to a sufficiently small value in order to permit the generation of a reasonably smooth curve 2 mmHg will usually do If the generation of a curve of average cardiac output versus average systemic arterial pressure is required the Pv parameter should be held constant by setting the Pvs parameter to a very large value 100 mmHg will usually be more than sufficient and the Pas parameter should be set to a sufficiently small value in order to allow the generation of a reasonably smooth curve 30 mmHg will usually do Finally note that the researcher may assign sufficiently small values to both Pvs and Pas such that a family of cardiac output curves at different systemic arterial pressures will be generated 26 5 5 Viewing Examples The following examples illustrate how to view
51. rces during a single simulation The initial pressure volume and flow rate of the preparation are computed with the function lv_init_cond m and 50 0 0 1 0 2 0 3 0 4 0 5 Frequency Hz Figure 22 Model red and experimental blue supine posture heart rate power spectra at fixed rate breathing of 0 25 Hz The dark blue line is the average spectrum computed from 14 volunteers while the two lighter blue lines are the corresponding 95 confidence intervals See text for additional details 51 the derivative of the pressure at a desired time step is determined with the function lv_eval_deriv m Intact circulatory preparation for measurement of single ventricular contraction P t response The electrical circuit analog of this preparation is given by Figure land in cludes an additional parameter nve which represents the beat number after which the ventricles will no longer contract The single ventricular contraction P t response may then be determined by executing the preparation for nve and then nve 1 ven tricular contractions and then taking the difference between the two resulting P t waveforms Intact circulatory preparation with only linear elements The electrical circuit analog of this preparation is given by Figure 1 in which the four nonlinear elements are re placed by purely linear elements This model was previously presented by Davis 3 The initial pressures volumes and flow rates of the preparation
52. rch gt Help Quit SENS MAS CEREZO properties SS ESA ES GE eS Horni Gaui N N N parameters_6 4 0358 1 18 Grid intervals 0 2 sec x 0 5 mV Figure 14 WAVE window generated according to the first parameter update of Ex 6 36 6 4 Record temp qrs File v View Edit y Properties lt Search lt lt lt Find gt gt gt Search gt Help Quit Giller GEAT Pero partiesira GESTA CESS ES A N N parameters_B 2 1 58 2 18 Grid intervals 0 2 sec x 0 5 mV Figure 15 WAVE window generated according to the second parameter update of Ex 6 37 First on line hemmorhage of 500 ml Then on line initiation of arterial and cardiopul monary baroreflex control e Required Steps 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters _7 2 Open the file parameters_7 with any text editor e g emacs 3 Re assign the following parameters waveform 1 26 baro 3 bgain 0 again 0 and pgain 0 4 Save the file parameters_7 5 Run the following command at the Linux prompt rcvsim parameters_7 foo7 6 Some time in the midst of the simulation type p followed by lt RETURN gt at stan dard input 7 Re assign the the following parameter Otot 4500 8 Save the file parameters_7 9 Type followed by lt RETURN gt at standard input 10 At a subsequent time during the simulation type p followed by lt RETURN gt at s
53. red standard deviation stdwq that is bandlimited to a desired frequency f coq These fluctuations may specifically be due to for example fast acting hormonal loops These fluctuations are generated with the function bl_filt m In order to implement all of the above models rather than using read_param m the parameter vec tor th must be created by first copying the file DIR bin header def m to the current directory and then executing th header_def at the MATLAB prompt Note that header_def m can be copied to any name as long as it has the extension m Additionally the appropriate option of the arguments to simulate mexlx type help simulate at the MATLAB prompt must be selected 53 References 1 Ronald D Berger J Phillip Saul and Richard J Cohen Assessment of autonomic response by broad band respiration IEEE Trans Biomed Eng 36 11 1061 1065 1989 2 Kevin Patrick Clark Extracting new information from the shape of the blood pressure pulse Master s thesis Massachusetts Institute of Technology Cambridge MA 02139 February 1990 3 LL Timothy L Davis Teaching physiology through interactive simulation of hemodynamics Master s thesis Massachusetts Institute of Technology Cambridge MA 02139 February 1991 4 a Ramakrishna Mukkamala A Forward Model Based Analysis of Cardiovascular System Iden tification Methods PhD thesis Massachusetts Institute of Technology Cambridge MA 02139 June 2000
54. ribed above 20 CrmukkamaBcvsim src revsim h The function rcvsim executes a computational model of the cardiovascular system The model includes the following components 1 lumped parameter pulsatile heart and circulation intact heart lung unit or systemic circulation 2 short term regulatory system a arterial baroreflex system b cardiopulmonary baroreflex system c direct neural coupling mechanism between respiration and heart rate resting physiologic perturbations a respiration b autoregulation of local vascular beds bandlimited disturbance to systemic arterial resistance c 1 f disturbance to heart rate Command line arguments revsim parameterfile outputfile where parameterfile name of working file which contains the current parameter values characterizing the model must be in current directory outputfile prefix of the output files generated by the model or revsim h for help Output files outputfile dat binary file MIT format shorts containing all generated waveforms outputfile grs qrs annotations file MIT format outputfile hea header file MIT format describing the contents of outputfile dat outputfile txt ascii multi column file representing either cardiac function or venous return curves parameterfile num parameter file characterizing execution created after each parameter update beginning with the initial choice of values num 0 see aux information in outputfile qrs
55. s 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters_9 2 Open the file parameters_9 with any text editor e g emacs 3 Re assign the following parameters time 1000 waveform 1 preparation 2 and Crds 5 4 Save the file parameters_9 40 Record temp File View Edit Properties 7 lt Search lt lt lt Find gt gt gt Search gt Help Quit Sue Edite ES Es ES pe ee Grid intervals 0 2 sec x 0 5 mV Figure 17 WAVE window generated according to Ex 8 41 Gnuplot mgl mgu l min 6 mPra mmHg Figure 18 Gnuplot window generated according to Ex 8 Ex 10 and Ex 11 42 5 Run the following command at the Linux prompt rcvsim parameters _9 foo9 e Execution Output The Gnuplot window of Figure 19 will appear immediately following the calculation of the entire venous return curve The following files will be created in the current directory foo9 dat foo9 qrs foo9 hea Ex 10 foo9 txt and parameters _9 0 e Desired Execution On line display of multiple cardiac output and venous return curves Uncontrolled unperturbed heart lung unit and systemic circulation preparations with default parameter values and after a 25 increase in systemic arterial resistance mean systemic pressure heart rate and contractility e Required Steps 1 Copy file DIR bin parame
56. se on PhysioNet 4 Another research example which illustrates how RCVSIM may be utilized in conjunction with the open source software and exper imental data sets of PhysioNet in order to improve the accuracy of the model and thus possibly physiologic understanding is provided below 47 Gnuplot mgl l min 5 5 5 4 5 4 3 5 3 2 5 2 pl 1 0 5 mPa mmHg Figure 21 Gnuplot window generated according to Ex 12 and Ex 13 48 The default or nominal parameter values of the human cardiovascular model are set such that the power spectra of the simulated beat to beat hemodynamic variability resembles power spectra measured from a group of normal humans in the standing posture 4 5 The objective of the re search example here is to determine a set of parameter values which permit the model to generate a realistic supine posture heart rate power spectrum In order to address this objective it is neces sary to obtain experimental data sets to define what is realistic and software to compute the heart rate power spectrum both of which are available from PhysioNet The specific steps which were implemented to achieve the research objective are given below 1 Establish realistic supine posture heart rate power spectrum a Visit the following web page http www physionet org physiobank database meditation data which houses Exaggerated Heart Rate Oscillations During two Meditation Techniques Data
57. siologic pertur bations models Because of the relatively narrow bandwidths of these models the parameter adjustments are calculated at a sampling period of 0 0625 s First the requisite waveforms originally computed at a sampling period of T are decimated to a sampling period of 0 0625 s by averaging over the past 0 25 s every 0 0625 s Then the mandated parameter adjust ments are computed at a sampling period of 0 0625 s Finally the mandated parameter adjustments are converted to a sampling period of T via linear interpolation with the ex ception of the adjustments to C7 which do not take effect until the initiation of the next ventricular contraction in order to compute the subsequent waveforms e Establishing qrs via Integrate and Fire The mandated changes to F t are mapped to the times of onset of ventricular contraction by integrating F t in units of bps over time until the integral is equal to one Then systole is initiated by resetting the variable ventricular elastance model the integral is set to zero and the integration is repeated e Heart Lung Unit or Systemic Circulation 25 Varying P P C amp 4 and Averaging P q t do t Cardiac function or venous return curves are generated if desired Following every fifth beat P and P are varied in steps for generation of cardiac function curves and C4 is varied for simulation of venous return curves Time averaged P a t and q t and P for cardiac funct
58. st be the desired prefix name of the output files to be generated by the model By executing rcvsim with these two arguments three MIT format files are always generated in the current directory with extensions dat qrs and hea The dat file is a binary shorts file consisting of all of the generated waveforms the qrs file is a binary file consisting of annotations which include the times of onset of ventricular contractions as well as any parameter updates and the hea file is an ASCII header file necessary for reading viewing and analyzing the dat and qrs files with the open source software provided by PhysioNet A fourth file with the extension txt may also be generated when the heart lung unit preparation or systemic circulation preparation is implemented This file is in ASCII multi column format and constitutes the simulated cardiac function or venous return curves In order to document fully the simulation the rcvsim executable also saves the working parameter file in the current directory each time it is updated The name of the saved files is the first command line argument with the extension num which denotes the number of parameter updates that have been made during the simulation period The name of each saved file is also recorded in the annotation files at the time in which the parameters were updated At the beginning of the simulation the rcvsim executable saves the initial working parameter file with extension 0 to the curr
59. status of the current simulation based on the current parameter values the previous parameter values and the status parameters see Section 5 2 e conserve_vol m computes the pressures at the current time step necessary to conserve the blood volume in each compartment at the current time step when parameter values are up dated e read_param m reads a file which contains the parameters values of the cardiovascular model and its execution in a specific format and stores the values ina MATLAB vector e read_key c reads the standard input pauses the simulation if a p is entered followed by lt RETURN gt and resumes the simulation if a t is entered followed by lt RETURN gt e write_param c copies the parameter file to a new file of the same name but with the extension num This function is implemented when the parameter update occurs The extension is set equal to the number of parameter updates that have been made during the simulation period e wave_remote c plots the desired simulated waveforms and annotations with the WAVE dis play system This function is called when the simulated data are written to file in MIT format and plots the most recent desired window of written data The function simulate m is called by a wrapper function rcvsim m for execution at the Linux prompt This wrapper function takes two command line arguments 1 the name of a file con taining the desired parameter values and 2 the prefix name of the ou
60. sture heart rate power spectra match see Figure 22 As expected the parameter changes from the stand ing posture to supine posture reflected a shift in autonomic balance favoring the parasympathetic nervous system Interestingly a further comparison of these parameter values with the nominal values suggests that the posture peak in humans 0 1 Hz 10 present in the model with default parameter values could be due to both a system resonance which is established by increased sym pathetic nervous activity as well as increased fluctuations in local vascular resistance beds which may be due to increased leg muscle activity A Other Models In addition to the models of Section 2 other lumped parameter models of the pulsatile heart and circulation and resting physiologic perturbation models may be implemented with the RCVSIM source code These models may only be implemented at the MATLAB prompt by executing sim ulate mexlx A brief description of each of these models and the relevant MATLAB functions is given below e Lumped parameter models of the pulsatile heart and circulation Left ventricle preparation The electrical circuit analog of this preparation may be visualized by replacing Ca and Cry in Figure 1 with the DC voltage sources P and Pov respectively This preparation may be utilized for the analysis of the input output properties of the left ventricle model however there is currently no source code to alter the DC voltage sou
61. t time step Q 01 t which may vary due to integration error is conserved The difference between the computed Q t and its assigned value is added removed from Q t and P t is altered accordingly e Parameter Updates a Conserving Q t and Documenting Updates The parameter values of a simulation may be updated after the initiation of each ventricular contraction by pausing the simulation updating the parameter values and resuming the simulation The newly cho sen parameter values are documented to file if they are relevant to the current simulation and the blood volumes in each compartment at the current time step are conserved by adjusting the pressures at the current time step if necessary Adjustments to the respiratory related waveforms are implemented for the remainder of the integration period e Calculating q t The flow rates of the pulsatile heart and circulation models are calculated at the current time step from the pressures at the current time step e On Line Viewing 2 Writing Waveforms to MIT Format Files 22 Displaying Waveforms When viewing simulated data as they are being calculated the waveforms are periodically written to file in MIT format with a desired period The newly written data are then imme diately displayed with WAVE The flow of each of the blocks is then repeated starting at Numerical Integration for Calculating P t with t t T In order to execute the blocks in the flowchart simulate m
62. tallation and Compilation The researcher may download the RCVSIM software from PhysioNet and install and execute the pre compiled binaries provided that he is running Linux If the researcher also has access to MAT LAB and its compiler version 1 2 then he may modify and extend the source code as he wishes and then recompile it to create new binaries Alternatively if the researcher is running any other platform in which the WAVE display system is fully supported e g Solaris SunOS and has access to the MATLAB compiler version 1 2 he may compile the source code and install and execute the new binaries on that platform The binaries created for such platforms may then be uploaded to PhysioNet so that they may be distributed to other researchers who do not own MATLAB Detailed instructions on installing the RCVSIM binaries and required libraries and compiling the source code are provided below 16 4 1 Installation The installation steps that the researcher must carry out in order to execute the RCVSIM pre compiled Linux binaries are as follows 1 Download the file rcvsim tar gz from the following web page http www physionet org physiotools rcvsim 2 Type the following commands at the Linux prompt tar xvzf rcvsim tar gz cd revsim The contents of this directory henceforth referred to as DIR are as follows e README This text file includes a brief introduction references to the INSTALL file and the doc sub dir
63. tandard input 11 Re assign the the following parameters bgain 1 again 1 and pgain 1 12 Save the file parameters_7 13 Type Y followed by lt RETURN gt at standard input e Execution Output A WAVE window will appear and will automatically scroll through the simulated data with annotations The automatic scrolling will stop once Step 6 is executed After Steps 7 9 are executed automatic scrolling will resume until Step 10 has been ex ecuted When Steps 11 13 are executed the automatic scrolling will resume until a total of 300 seconds of data have been simulated Figure 16 illustrates the WAVE win dow once the simulation is complete The Time variable of the WAVE window is set such that the waveforms over the entire simulation period may be viewed all at once Note how systemic arterial pressure has been returned to near normal values with the baroreflex systems The following files will be created in the current directory foo7 dat foo7 qrs foo7 hea parameters_7 0 parameters_7 1 and parameters 7 2 Ex 8 e Desired Execution 38 6 4 Record temp qrs File T View Edit 7 _Properties T lt Search E ES Find gt gt gt Search gt _Help Quit 5109 Grid intervals 0 2 sec x 0 5 mV Figure 16 WAVE window generated according to Ex 7 in which the time duration of the window has been expanded to illustrate the entire simulation period 39 On line d
64. ters def to the current directory with the new file name pa rameters_10 Open the file parameters_10 with any text editor e g emacs 3 Re assign the following parameters time 1000 waveform 1 preparation 1 Pas 1000 and Pvs 2 Save the file parameters_10 5 Run the following command at the Linux prompt 10 11 12 13 rcvsim parameters_10 fool0a Once the simulation is complete re assign the following parameters numerics 1 preparation 2 and Crds 5 Save the file parameters_10 Run the following command at the Linux prompt rcvsim parameters _10 foo10b Once the simulation is complete re assign the following parameters Ra 1 25 and Pms 8 625 Save the file parameters_10 Run the following command at the Linux prompt rcvsim parameters _10 foo10c Once the simulation is complete re assign the following parameters preparation 1 Cls 0 3 Crs 0 9 and F 1 5 Save the file parameters _10 43 Gnuplot mgl mgu l min mPra mmHg Figure 19 Gnuplot window generated according to Ex 9 Gnuplot mql mqu l min 14 mPra mmHgl Figure 20 Gnuplot window generated according to Ex 10 and Ex 11 14 Run the following command at the Linux prompt rcvsim parameters_10 fool0d e Execution Output A total of four Gnuplot windows will be displayed beginning with a window displaying a single cardiac output curve see Figure 18 then a wi
65. the researcher may develop and evaluate inverse modeling algorithms for determining important cardiovascular parameters from experimental data Experimental studies in turn permit the re searcher to construct more accurate computational models thereby improving the researcher s un derstanding of the cardiovascular system and ability to devise new experimental hypotheses and inverse modeling algorithms The general aim of this document is to introduce the Research CardioVascular SIMulator RCVSIM software which may be downloaded from PhysioNet www physionet org an NIH funded national research resource that provides well characterized experimental data sets and open source software for their analysis RCVSIM is capable of generating reasonable human pul satile hemodynamic waveforms cardiac function and venous return curves and beat to beat hemo dynamic variability The data simulated by RCVSIM is written in a format which is identical to the experimental data sets As such the open source data analysis software may be readily applied to the simulated data as well The data generated by RCVSIM may be viewed as they are being calculated on line viewing or any time after they have been calculated off line viewing with the WAVE display system which is also provided by PhysioNet and Gnuplot The RCVSIM software is Open source and extensively commented and includes Linux binaries that may be executed at the Linux or MATLAB prompts It should
66. tput files to be generated in MIT format The function rcvsim m which also includes a help option reads in the parameter file with read_param m see above creates a header file in MIT format executes simulate m writes the simulated data to MIT format files if the on line viewing option is not chosen and displays cardiac function and venous return curves if desired with the function plot_cfvr c which employs Gnuplot In order to execute rcvsim m the function must be compiled with the file make m which creates the binary file rcvsim The function simulate m may also be compiled independently of rcvsim m with the file makem m which creates the binary file simulate mexlx in the Linux en vironment Each of these make files greatly improve execution speed specifically through mcc MATLAB compiler optimization arguments r real numbers only and i no dynamic memory allocation Note that simulate m may only be executed in the MATLAB environment without on line viewing and parameter updating capabilities 14 3 2 Modifications and Extensions Although the human cardiovascular model upon which RCVSIM is based accounts for a wide vari ety of hemodynamic behaviors it certainly cannot address arbitrary cardiovascular research objec tives For example if the researcher is interested in analyzing how stroke volume is compromised at very high heart rates gt 150 bpm in the absence of cardiovascular regulation the model as described in Section
67. ve the latest compiler so it may be possible in the future to use this compiler 5 Software Execution The researcher may view and record data simulated from the human cardiovascular model of Section 2 by running the rcvsim executable file at the Linux prompt Detailed instructions ex plaining how to execute this file including several examples are provided below Execution of simulate mexlx at the MATLAB prompt is touched upon in Appendix A Note that this section requires some familiarity with the WAVE display system which may be acquired by either typing more usr help wave wave hip at the Linux prompt or visiting the web page http www physionet org physiotools wug 19 5 1 Help Option A help option may be implemented by running the rcvsim executable with the single argument h at the Linux prompt that is rcvsim h see Figure 8 The help option provides a description of the major components of the human cardiovascular model command line arguments generated output files and on line viewing options According to the help option the executable file requires two arguments at the command line in order to simulate hemodynamic data The first argument must be the name of a file in the current directory which contains the desired parameter values characterizing the human cardiovascular model and its execution This is the working parameter file which may be updated during the simulation period see Section 5 2 The second argument mu
68. waveforms and cardiac function venous return curves on line and off line Prior to implementing these examples the researcher should set the time duration displayed by the WAVE window to 20 seconds by resizing the window and or ad justing the Time scale variable click VIEW option at the top of the WAVE menu bar Ex 1 e Desired Execution On line display of left ventricle pressure volume and flow rate Uncontrolled unperturbed intact pulsatile heart and circulation with default parameter values e Required Steps 1 Copy file DIR bin parameters def to the current directory with the new file name pa rameters_l 2 Open the file parameters_1 with any text editor e g emacs 3 Re assign the following parameters waveform 0 9 17 and annotations 0 Make sure all of the status parameters are set to zero 4 Save the file parameters_l 5 Run the following command at the Linux prompt rcvsim parameters_1 fool e Execution Output The WAVE window in Figure 10 will initially appear and will automatically scroll through the simulated data as they are being generated This process will terminate once 300 seconds of the data have been simulated The following files will be created in the current directory foo1 dat fool qrs fool hea and parameters_1 0 which may subsequently be viewed off line See Example 2 Ex 2 e Desired Execution Off line display of left ventricle pressure volume and flow rate
69. y lt RETURN gt at standard input Re assign the the following parameter Ofrs 500 Save the file parameters_6 Type fr followed by lt RETURN gt at standard input e Execution Output A WAVE window will appear and will automatically scroll through the simulated data with annotations The automatic scrolling will stop once Step 6 is executed After Steps 7 9 are executed automatic scrolling will resume until Step 10 has been ex ecuted When Steps 11 13 are executed the automatic scrolling will resume until a total of 300 seconds of data have been simulated Figure 14 illustrates the WAVE win dow during the reduction in lung compliance Note that this reduction does not alter instantaneous lung volume see Section 5 3 2 Figure 15 illustrates the WAVE window during the time of the step increase in the functional reserve volume of the lungs Note that the step increase occurs once the current respiratory cycle is complete The following files will be created in the current directory foo6 dat foo6 qrs foo6 hea Ex 7 parameters_6 0 parameters_6 1 and parameters 6 2 e Desired Execution On line display of systemic arterial pressure and heart rate with annotations Uncontrolled unperturbed intact pulsatile heart and circulation initially with default parameter values 35 E 6 4 Record temp qrs File View Edit y Properties lt Search lt lt lt Find gt gt gt Sea
70. y adjusting the value of C t at end diastole C in order to vary Pea t the pressure that impedes flow into the right ventricle and time averaging the resulting t and Pea t Note that the independent current source here q t keeps the mean systemic ms pressure precisely constant throughout the measurement period by pumping into the systemic circulation whatever is pumped out F t es Pulsatile C L t Heart pp ANS 0 Palt Ra Circulation Baroreceptors Figure 4 Block diagram of the feedback system depicting the arterial baroreflex arc 2 2 Short Term Regulatory System The arterial baroreflex arc is implemented according to the feedback system illustrated in Figure 4 This system is aimed at tracking a setpoint sp pressure through the following sequence of events The baroreceptors sense P t and relay this pressure to the autonomic nervous system ANS The ANS compares the deviation between the sensed pressure and PP with zero and then responds by adjusting four parameters of the pulsatile heart and circulation in order to keep the ensuing P t near PP The four adjustable parameters are F t C t at end systole Cf t Q9 t and R t The ANS controls these parameters based on the history of P t P specifically according to the following nonlinear dynamical mapping Pa t 7 P ap t Gwo G s

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