2.6 Cardiovascular Computer Simulation

Transcription

1 2.6 Cardiovascular Computer Simulation ROOM 23G22 Contents 1. INTRODUCTION GENERAL REMARKS LEARNING GOALS PHYSIOLOGICAL PARAMETERS GLOSSARY USING THE COMPUTER PROGRAM THE TOOL BAR DIAGRAM AND PLOTS SOFTWARE CLABUZH EXPERIMENTS USING THE MODEL OF AN ISOLATED HEART (IHL) PRESSURE CHANGES DURING THE CARDIAC CYCLE... 9 Goals... 9 Method... 9 Effect of heart rate on systole and diastole duration CHANGES TO THE VENTRICULAR VOLUME DURING THE CARDIAC CYCLE Goal Method Effect of heart rate on stroke volume and cardiac output Mechanisms to obtain an increased stroke volume with a higher heart rate

2 3.3. EFFECT OF FILLING PRESSURE ON STROKE VOLUME (FRANK-STARLING LAW) Introduction Goal Method Impact of filling pressure (intracardial regulation, Frank-Starling Mechanism) on stroke volume at different inotropic states (extracardial Regulation, Sarnoff- Mechanism) EFFECT OF MEAN ARTERIAL PRESSURE ( AFTERLOAD) ON STROKE VOLUME (SV, HSV) 16 Introduction Goals Method Influence of mean arterial pressure ( Nachlast, afterload) on SV (HSV), for different contractility (inotropy) states EFFECT OF VESSEL ELASTICITY ON BLOOD PRESSURE Introduction Goal Method Blood pressure with ageing (reduced compliance) Questions for Part EXPERIMENTS ON THE CLOSED LOOP MODEL (CCL) INFLUENCE OF BLOOD VOLUME ON CVP (ZVD) Introduction Goals Method Effect of Blood volume on CVP THE INFLUENCE OF CO (HMV) AND PERIPHERAL RESISTANCE ON MEAN ARTERIAL PRESSURE Introduction Goals Method Influence of HR on CO (HMV) and on mean arterial pressure for different TPR ISOLATED LEFT HEART INSUFFICIENCY AND INCREASES IN PULMONARY VASCULAR RESISTANCE

3 Introduction Goal Method Results and analysis HOW THE ACTIVATION OF THE SYMPATHETIC AND INHIBITION OF THE PARASYMPATHETIC NERVOUS SYSTEMS PREVENTS A LOSS OF BLOOD PRESSURE UNDER LOAD (SEE ERGOMETRY LAB CLASS) AND STANDING (SEE ORTHOSTATICS LAB CLASS) Introduction Goal Method

4 1. Introduction 1.1. General remarks Many factors regulate heart rate and stroke volume and the resulting cardiac output. Often several regulatory mechanisms act simultaneously and influence each other, which make it difficult to separate and to understand their individual effects. Therefore, it is extremely helpful to simulate the physiological processes in cardiovascular system by means of a computer model. The principle of this model is very simple: you can selectively display the components of the model (e.g. left ventricle with the input and output blood vessels) on the computer screen. The model variables are displayed directly and you can vary them simply by a mouse click. You can follow and interpret changes of the measured variables (e.g. ventricular pressure and volume) that occur during the cardiac cycle by directly observing them on the screen. In this way, you will be able to answer simple and complex questions and you can independently test hypotheses concerning the possible outcome of changing the different variables. One disadvantage of the simulation is the lack of the typical variability of measured values, inherent to the measurements in vivo. Furthermore, the number of variables in model is less than for in vivo situations, and the number of possible answers given by the model is limited. The model is based on experiments performed on an isolated, denervated preparation Learning goals To understand cardiac function in detail To identify the most important regulatory mechanisms for stroke volume To understand better the hemodynamics of the circulatory system To know which factors change the blood pressure and the underlying mechanism -4-

5 1.3. Physiological parameters Enter the typical values for an adult. Blood pressure in body circulation: Arteries: P Systolic = mmhg P Diastolic = mmhg V. Cava: P Venous = mmhg ZVD Preload RV Blood pressure in pulmonary circulation: Arteries: P A.Pulmonalis Systole = mmhg P A.Pulmonalis Diastole = mmhg V. Pulmonalis: P V.Pulmonalis = mmhg Preload LV Heart rate (at rest): Stroke volume: Cardiac output: Hf = /min HSV = ml HMV = CO = l/min 1.4. Glossary EN DE Afterload Nachlast ( Druck in der Aorta [Wandspannung]) Aortic Root Compliance Mündungsstelle des linken Ventrikels in die Aorta Dehnbarkeit = ΔV / ΔP (Kehrwert des Volumenelastizitätskoeffizienten Contractility Kontraktilität Herz Kontraktionskraft (= Inotropie) CVP ZVD Central Venous Pressure / Zentraler Venendruck HR Hf Heart Rate / Herzfrequenz Preload Vorlast ( dem Füllungsdruck [Wandspannung]) RV, LV TLR TPR Rechter Ventrikel, Linker Ventrikel = Total Lung Resistance Totaler Gefässwiderstand im Lungenkreislauf = Total Peripheral Resistance Totale Gefässwiderstand im Körperkreislauf CO HMV = Cardic Output / Herz-Minutenvolumen Totaler Blutauswurf des Herzens pro Minute SV HSV = Stroke Volume / Herz-Schlagvolumen Blutauswurf pro Herzschlag EDV ESV = End-diastolic volume / Enddiastolisches Ventrikelvolumen = End-systolic volume / Endsystolisches Ventrikelvolumen -5-

6 2. Using the computer program Start the Cardiovascular Function Lab -program by double clicking on the icon (CLabUZH) The tool bar Button Function Speed: Simulation start /stop Select simulation speed Model: IHL: Isolated Heart Lab CCL: Closed Circulation Lab Reset Reset all parameters of current model to their initial values -6-

7 2.2. Diagram and plots Figure 1. CFL overview (model of an isolated heart: IHL) Three plots of the measured values are displayed (pressure-volume/pressuretime/volume time plots) in the upper part of the window. When you move the mouse cursor over the plot, you can read of the corresponding values. Remember to stop the simulation first before reading values. The lower half of the screen shows the experimental arrangement. You can change the model parameters by entering the values in the boxes Software CLabUZH free download from the uzh Institute of Physiology webside

8 3. Experiments using the model of an isolated heart (IHL) (See Fig 1) Check that the IHL model is running (IHL-Button activated). The model comprises 4 main components: venous blood inflow (Vv. pulmonalis), the pumping left ventricle, a piece of elastic vessel (aorta) and a peripheral resistance (TPR). Blood inflow in this model is assumed to come from an infinite source (this is not the same as the real situation), so that the Preload (CVP preload) can be predefined as a constant. Note: Although the graphics show both halves of the heart, only the left heart is active in the model. You can study the effects of the following variables on various parameters using this model: Variable Standard value CVPpulm Pulmonary venous pressure, filling pressure ( Vorlast = preload) 10 mmhg HR Heart rate (Hf) 70 min -1 Contractility Myocardial contractility (= Inotropy) 100 % TPR Total peripheral resistance 1.0 mmhg/(ml/s) Compliance Aortic compliance (ΔV / ΔP) 100% Table 1: Modifiable variables in IHL-Model. -8-

9 3.1. Pressure changes during the cardiac cycle Goals To become familiar with the phases of the cardiac cycle on the three plots (Pressure-time; volume-time; P-V) To relate the sequence of valve opening and closing in time and graphically To explain the time shift between ECG and ventricular and aortic pressure. To understand the physiological and pathophysiological effects of an increased heart rate. Method Set all variables to the default values [Reset]. I) Mark each mechanical phase of the heart cycle in IHL-Model (Fig 1): also indicate the start of the contraction phase (I) and ejection phase (II) of ventricular systole as well as the relaxation phase (III) and the filling phase (IV) of ventricular diastole in the 3 plots (Fig 1). Indicate which valves are open and closed (A-V (mitral) valve / Aortic valve)! II) Indicate the start and end of the electric systole in the plot below (Fig 2) using the ECG trace. III) Determine the effect of the heart rate on systole and diastole duration. Increase the heart rate stepwise (do not change the other variables!) and measure the diastole from the pressure curve on the screen using the mouse cursor. Plot 1) the absolute systole and diastole duration (in seconds) and 2) the relative systole and diastole duration (as % of the cycle period) as a function of the heart rate. Note how the systolic and diastolic pressures change with increasing heart rate. Tip: You can read of the difference directly by keeping the left button pressed and moving the mouse cursor over the plot. -9-

10 Effect of heart rate on systole and diastole duration Heart rate [min -1 ] Period of cycle [s] Diastole [s] Systole [s] Diastole [%] Systole [%] Generate the plot (enter the results in the corresponding worksheet of the Excel file 'Excel 2.6 Computersimulation'). The plot is made automatically: Systole and diastole are shown as a function of heart rate. Explain the observed changes. What is the significance of diastole on the coronary circulation? What measures would be necessary in the case of coronary heart disease?

11 Fig 2. The cardiac cycle (from Color Atlas of Physiology, 2003 Thieme) -11-

12 3.2. Changes to the ventricular volume during the cardiac cycle Goal To investigate the dependence of stroke volume and cardiac output on heart rate. Method Set all variables to the default values [Reset]. I) Note changes in ventricular volume during systole and diastole (Volume-Time plot and Fig.2). How does this relate to the ECG? II) Determine the dependence of stroke volume and cardiac output on heart rate. Increase the heart rate stepwise and the stroke volume and cardiac output values acquired will be displayed as a function of heart rate (Excel). Note: After each change in a parameter, allow sufficient time for a steadystate to be reached before recording the value. Effect of heart rate on stroke volume and cardiac output Heart rate [min -1 ] SV (HSV) [ml] CO (HMV) [l/min] Generate the graph (Excel): Stroke and cardiac output as a function of heart rate -12-

13 III) Consider what changes would be necessary to return the reduced stroke volume with a heart rate of 140 min -1 back to its normal value of 70 ml. Test your predictions using the model and enter the required changes for the compensation mechanism in the table. Mechanisms to obtain an increased stroke volume with a higher heart rate Compensatory mechanism Compensation value (units)

14 3.3. Effect of filling pressure on stroke volume (Frank-Starling law) Introduction Define and explain the term Preload (Vorlast): The increased stroke work that results from an increased filling pressure (central venous pressure, CVP/ZVD) depends on the length-tension relationship for cardiac muscle fibres. It is called the Frank-Starling mechanism, after its discoverers. The increased stroke work (increased contractility, positive inotropy) due to exogenous factors (sympathetic tonus) is also referred to as the Sarnoff mechanism. Goal Understand the Frank-Starling-Mechanism: the influence of filling pressure (CVP/ZVD Vorlast/preload) on stroke volume Understand the Sarnoff-Mechanism (increased contractility, positive inotropy) Method Set all variables to the default values [Reset]. I) Distinguish between the effects of the Frank-Starling-Mechanism and those of extra-cardial regulation of the myocardium (nervousness, hormones, also after medication) on the stroke volume. Increase stepwise the CVP (ZVD) from a minimal value to investigate how an increased CVP (filling pressure Vorlast, preload) increases the stroke volume. Each time, wait for a steady-state to be reached before adding the value to the graph. Repeat this for different contractility values. -14-

15 Impact of filling pressure (intracardial regulation, Frank-Starling Mechanism) on stroke volume at different inotropic states (extracardial Regulation, Sarnoff-Mechanism) Preload [mmhg] Stroke volume Contractility = 50 Contractility = 100 Contractility = 150 % Generate the graph (Excel): Dependence of stroke volume on filling pressure (CVP) and on the contractility (Inotropy) of the heart. Compare the effects of intra- and extra-cardiac regulation on stroke volume using the P-V plot and the curves. -15-

16 3.4. Effect of mean arterial pressure ( afterload) on stroke volume (SV, HSV) Introduction Define and explain the term Afterload (Nachlast): Because the aotic pressure ( Nachlast, Afterload) changes continually during the cardiac cycle so that a simple determination is not possible, in practice it is often equated with the diastolic pressure. Nevertheless, the program calculates the exact mean arterial pressure for each cardiac cycle (shown on the display as mean). Goals Understand the influence of the mean arterial pressure ( Nachlast, Afterload) on stroke volume (SV, HSV) Understand the influence of strength of contraction (contractility, inotropy) on stroke volume for different mean arterial pressures ( Nachlast, Afterload) Method Set all variables to the default values [Reset]. I) Investigate the effect of peripheral resistance (TPR) on stroke volume (HSV). Repeat the complete series of measurements for a weak (Contractility = 50 %) and strong (Contractility = 150 %) heart. -16-

17 Influence of mean arterial pressure ( Nachlast, afterload) on SV (HSV), for different contractility (inotropy) states TPR (mmhg / (l/min)) Contractility = 50 % Pmean in Aorta (mmhg) HSV (stroke volume) Contractility = 100 % Pmean in Aorta (mmhg) HSV (stroke volume) Contractility = 150 % Pmean in Aorta (mmhg) HSV (stroke volume) (ml) Generate the plot (Excel): Dependence of stroke volume on mean arterial pressure ( Nachlast, afterload) for different strength of contraction (contractility, inotropy) What do you deduce from the curve shape concerning possible therapeutic strategies for treating a weak heart condition (inotropy = 50%)? -17-

18 3.5. Effect of vessel elasticity on blood pressure Introduction The vessel compliance (=Dehnbarkeit) decreases with age, whereas the vessel resistance increases. This has a directly measurable effect on blood pressure variation. Goal To study the effect of physiological ageing of the aorta on the blood pressure variation, and in particular on the pulse pressure. Method Set all variables to the default values [Reset]. I) Reduce the compliance of the aorta in steps as indicated and observe the arterial blood pressure (systolic, diastolic, mean and pulse pressure) In the experiment, changes in TPR, preload and inotropy are not taken into account. Blood pressure with ageing (reduced compliance) Compliance ml/mmhg PSystole (mmhg) PMean (mmhg) PDiastole (mmhg) Pulse pressure (mmhg) Generate graphs of the data (Excel). Interpret your graphs. -18-

19 Questions for Part 3 Which variable(s) influence the mean arterial and diastolic pressures (for normal / or given SV (HSV))? Ohm s law for circulation: What does 'Pulse pressure' mean? The pulse pressure is a measure of.. Explain the changes in diastolic pressure (taken as the mean arterial pressure) with increasing heart rate and constant CVP (ZVD): Explain the changes in systolic pressure with increasing heart rate and constant CVP (ZVD): What is the relationship between diastole and the left coronary circulation? What are useful measures to treat coronary heart disease? -19-

20 4. Experiments on the closed loop model (CCL) Figure 3 The CCL-Model (Position of the heart in the circulatory system is not anatomically correct) After the experiments on the isolated heart, we will now focus on the circulatory system. The model uses a simplified circulatory system that comprises the body circulation and the pulmonary circulation. Both comprise adjustable vessel resistances (TPR: Total peripheral resistance / TLR: Total pulmonary resistance) and each has a manometer and two points that give the actual pressure. You can define the contractility (Inotropy) for each half of the heart. In vivo both ventricles are always influenced by the sympathetic nervous system in the same way. For the simulations, the artificial separation will help you display the underlying process and understand the effects of pathological changes better. The program calculates the Cardiac Output: CO (HMV: Herzminutenvolumen) and the chamber volumes (EDV / ESV) and you can read these directly from the graphical display. You can study the influence of the following variables on different measurement parameters: -20-

21 Variable Blood Volume Total volume of circulating blood Standard value 5.4 l HR Heart rate(hf) 70 min -1 Contractility RV / LV Contractility (Inotropy) of left and right ventricles 100 % TPR Total peripheral resistance 1.0 mmhg/(ml/s) TLR Total resistance of pulmonary vessels 0.1 mmhg/(ml/s) Compliance Compliance of aorta (ΔV / P) 100 % Table 2: Adjustable variables in CCL-Model -21-

22 4.1. Influence of blood volume on CVP (ZVD) Introduction The CVP (central venous pressure/zvd) corresponds to the pressure in body veins in the vicinity of the heart and is almost identical to the pressure in the right atrium. For a normally functioning heart, the CVP (ZVD) is an indication of the total blood volume. The following experiments should illustrate this dependence. Goals To observe the dependence of CVP (ZVD) (PV. cava superior et inferior) on blood volume and understand their relationship Method Set all variables to the default values [Reset]. I) Increase the blood volume in steps from 5.0 l until you reach the maximum value. The mean venous pressure will be displayed as soon as the model reaches a steady state. Make a graph of the relationship. Effect of Blood volume on CVP Blood volume (l) CVP (mmhg) Graphic (Excel): dependence of CVP on blood volume Which other parameters can you change to give a similar increase in CVP? How can you distinguish between these different causes? -22-

23 4.2. The influence of CO (HMV) and peripheral resistance on mean arterial pressure Introduction In this experiment you will investigate how the mean arterial pressure is affected by the blood inflow and outflow. You can change the inflow by changing the heart rate and the outflow by changing the peripheral resistance. Goals Understand the influence of the CO (HMV) on mean arterial pressure Understand the influence of the peripheral resistance on the mean arterial pressure Method Set all variables to the default values [Reset]. I) Increase the heart rate stepwise and measure the stroke volume at each step. Calculate the CO and measure the mean arterial pressure. Enter both values as a function of the CO in the table. Carry out the experiment for TPR =0.6, 1.2, 2.0. Influence of HR on CO (HMV) and on mean arterial pressure for different TPR Hf (min -1 ) = 0.6 HMV (l/min) Pressure = 1.2 HMV (l/min) Pressure = 2.0 HMV (l/min) Pressure (mmhg) Generate graph (Excel): mean arterial pressure as a function of CO (HMV) and peripheral resistance. -23-

24 4.3. Isolated left heart insufficiency and increases in pulmonary vascular resistance. Introduction Various diseases can lead directly or indirectly to heart failure on the left or right side. This always leads to changes in the overall cardiovascular system. Goal To understand the mechanism of how changes in each loop can influence one another Method Set all variables to the default values [Reset]. I) Set the contractility of the left ventricle to 25%. Observe the resulting pressure changes. II) Set the contractility to the starting value and increase the TLR (Total Lung Resistance). Note the changes. Results and analysis In Experiment I) you can see the effect of a left heart insufficiency, as for example in the case of a heart attack. Experiment II) shows the effect of an increase in pulmonary vascular resistance (for example as a result of COPD, pulmonary fibrosis) whereby the increase in pressure in the pulmonary arteries has the opposite effect ( Pulmonary Hypertony). -24-

25 4.4. How the activation of the sympathetic and inhibition of the parasympathetic nervous systems prevents a loss of blood pressure under load (see Ergometry lab class) and standing (see Orthostatics lab class). Introduction For working muscles (e.g. Ergometry lab class) local vasodilation leads to a decrease in the flow resistance that in turn causes a decrease in the total peripheral resistance (TPR). When standing (e.g. Orthostatics lab class) the lower half of the body contains approximately 0.5 L blood more than when lying so that the return flow to the heart is reduced. In both cases the activation of the sympathetic and inhibition of the parasympathetic nervous systems respectively, protect against a decrease in blood pressure. Goal Understand the effect of the sympathetic nervous system on blood pressure by means of simulation Method Set all variables to the default values [Reset]. I) Simulate the effect of vasodilation in the working muscle by reducing the total peripheral resistance (TPR) to 0.6. Compensate the accompanying drop in mean arterial pressure (Pmean) by increasing the heart rate HR (Hf) and contractility (Contractility-RL and -LV). Measure the change in SV and pulse pressure and enter these in the table together with the altered measured values. -25-

26 Compensation for a decrease in total peripheral resistance during work by stimulating the sympathetic nervous system. Blood TPR HR Contr SV CO Pmean Ppulse Vol (l) mmhg l/min min -1 ml l/min mmhg mmhg Lying [Reset] Work without compensation Work + sympathetic stim. Effect Note: From experiment I) only the effect of the sympathetic nervous system on the HR and the contractility is simulated. Moreover the sympathetic activity limits the decrease in the TPR, such that an increase in the resistance in other areas occurs. II) Simulate the reduced backflow of blood resulting from standing, whereby the blood volume is reduced by 0.4 L. Compensate for the resulting decrease in mean arterial pressure (Pmean) by increasing the HR, the contractility (inotropy) and the TPR. Measure the change in the SV and pulse pressure and enter these values into the table as well as the changed and read values. Compensation for a decrease in return blood flow when standing (see Orthostatics lab class) resulting from sympathetic stimulation Blood TPR HR Contr SV CO Pmean Ppulse Vol (l) mmhg l/min min -1 ml l/min mmhg mmhg Lying [Reset] Standing without compensation Standing + sympathetic stim. Effect