the cardiovascular system
(the blood pressure regulation)

The model of the computer simulation program CARDIO is based on a model of Coleman (1980) of the cardiovascular system; of a healthy human being. It consists of five compartments: the heart, the vascular system, the intra- and extracellular fluid volumes, the nerve reflex system, and the kidney. The model contains a number of relations between parameters in these compartments and consists of about 60 variables.

Coleman's model of the blood pressure regulation and the cardiovascular system distinguishes three important regular quantities:

1. The extent of the vascular resistance is chiefly determined by metabolic and neural factors. In this way it is possible to keep the circulation of blood within the different tissues in the model as constant as possible (autoregulation) while adapting to system needs. The preservation of the flow within a number of tissues is one of the most important cardiovascular physiological priorities of the intact organism.
2. The mean arterial pressure; is acutely regulated by the nerve reflexes, notably the baroreceptor reflex (blood pressure regulation by the renin-angiotensin system is not included in CARDIO). In the long run blood pressure is regulated by the kidney function which controls the extracellular fluid volume.

3. The cardiac output is primarily determined by the venous return. Moreover the cardiac output can be directly influenced by the function of the heart as a pump.

Figure 9.1 The block diagram, also conceptual model, of the computer simulation program CARDIO. This model contains all the elements which play a role in regulating the blood pressure in a human body. The arrows indicate the intervention possibilities which the student can use for experiments.

Figure 9.1 contains a graph of the most important relations in the model. The interventions which are possible in this model and their points of application are mentioned in it. The most important variables of the model and their normal values are:

  • AP, Mean Arterial Pressure, 100 mmHg
  • CO, Cardiac Output , 5000 ml/min
  • TPR, Total Peripheral Resistance, 0.02 min.mmHg/ml
  • UO, Urine Output, 1 ml/min
  • HR, Heart Rate, 70 /min
  • BV, Blood Volume, 5000 ml
  • RAP, Right Atrial Pressure, 0 mmHg
  • CHEMO, Sympathetic nerve activity (chemoreceptor), 0
  • BARO, Sympathetic nerve activity (baroreceptor), 100% (=1)
  • SYMPS, Sympathetic Autonomic Outflow, 100 % (=1)
  • PO2, Arterial O2 Pressure, 100 mmHg
  • BUN, Blood Urea Nitrogen, 10 mg%
  • ECFV, Extra Cellular Fluid Volume, 15000 ml
  • MCFP, Mean Circ. Filling Pressure, 7 mmHg
  • GP, Glomerular Capillary Pressure, 60 mmHg
  • DELP, Pressure Gradient for Venus Return, 7 mmHg
  • RAR, Renal Artery Resistance, 1.67 min.mmHg/ml
  • BUNI, Urea Formation, 10 mg%
  • BUNO, Urea Excretion, 10 mg%
  • ED, Edema, 0
  • RVR, Resistance of the venous return, 0.0014 min.mmHg/ml

    Structure of the model
    The model underlying the computer simulation program CARDIO was further developed from Coleman's model and tested at the University of Limburg at Maastricht with the RLCS system and later on at the University of Twente with the computer simulation system MacTHESIS. The description of this model will be discussed relative to Pascal notation and to analogue notation, as well as to the manner in which these notations complement each other.

    The heart
    In the model the basic Cardiac Output (COB) -- i.e., the cardiac output without the influence of the autonomic nerve system -- is a function of the right atrial pressure (RAP). The cardiac output (CO) is determined by the basic cardiac output (COB) and a heart function parameter (HF). This heart function (HF) is a function of the right atrial pressure (RAP), the mean arterial pressure (AP), the sympathetic nerve activity (AO), possible cardiac glycoside (DIGI), and the basal heart strength (HSB).

    The circulation
    Many tissues in the body function optimally when the flow through the tissue of the organ remains constant within certain limits. The regulating mechanism that controls this tries to realize it through changes in the resistance. In this model an attempt has been made to include an overall description of the autoregulation phenomena. The mean arterial pressure is the product of the total peripheral resistance and the cardiac output:
    AP: = CO*TPR;

    Intra- and extracellular fluid volume
    The extracellular fluid volume (ECFV) is directly influenced by the fluid volumes which are taken in by the body minus those which leave the body:
    ECFV: = ECFV + (WIN - UO - BL)*dt;
    In the model ECFV(0) = 15000 ml and the intake and output is 1 ml/min. The water intake of the body (WIN) is set to 1 ml/min. The urine output (UO) is 1 ml/min and the loss of blood (BL) is normally 0 ml/min.

    The nerve reflex system
    The autonomic nervous activity (AO), the value of which in the normal situation is adjusted to 1, is dependent on the chemo and baroreceptor activity, a possible adrenergic blockade (BLOCK), a possible pheochromocytoma (PHEO) -- which develops an excessive sympathetic activity -- and a possible alpha-adrenergic influence of norepinephrine (NOREPI).

    The kidney
    The kidney function depends on the composition of the blood, aldosterone, neuronal factors, angiotensin, vasopressin, and the mean arterial pressure. In this model the basic urine output (UOB), normally 1 (ml/min), is a function of the mean arterial pressure (AP), the basal renal arterial resistance (RARB), the autonomic output (AP), and a vasodilatation factor (DILAT).
    The complete model written in Pascal is given by M?ller and Van Wijk van Brievingh (in press). In their book an executable MS.DOS version of CARDIO has been enclosed.
    Results (can be used in the exercise section)
    The normal values for the mean arterial pressure (AP), the cardiac output (CO), the total peripheral resistance (TPR), the urine output (UO) and the heart frequency (HR) in the computer simulation program CARDIO, with the given aggressive values and without any intervention are:

  • AP =100 mmHg;
  • CO=5000 ml/min;
  • TPR = 0.02 min.mmHg/ml;
  • UO =1 ml/min
  • HR =70 min.

    These 5 important hemodynamic variables can be supplemented by the extracellular fluid volume (ECFV), the blood volume (BV), or the pressure of the right atrium (RAP). These variables are normally not easy to measure. In the exercises described here such variables play an important role. The computer simulation program CARDIO not only gives visual feedback on the student interventions but also textual feedback.
    The following messages can appear on the screen when a particular variable reaches above or below a certain limit:

  • 40 < PO2 < 80 'Doctor, I can't get any air.'
  • 35 < PO2 < 40 'Doctor, I don't really know what's happening
  • to me anymore. I am losing my bearings.'
  • 30 < PO2 < 35 'Your patient is turning blue'.
  • PO2 < 30 'Your patient loses consciousness.'
  • AP < 85 'Doctor, I feel so dizzy.'
  • ED > 1 'Doctor, my feet are swollen, my shoes pinch.'