T.C.

BAHEEHR UNIVERSITY

CARDIOVASCULAR SYSTEM MOCK CIRCUIT

Capstone Project

Emir Gkberk Eken

STANBUL, 2012

T.C. BAHEEHR UNIVERSITY FACULTY OF ENGINEERING DEPARTMENT OF MECATRONICS ENGINEERING

CARDIOVASCULAR SYSTEM MOCK CIRCUIT

Capstone Project

Emir Gkberk Eken

Advisor: Dr. Kamuran KADIPAAOLU

STANBUL, 2012

T.C. BAHEEHR UNIVERSITY

FACULTY OF ENGINEERING DEPARTMENT OF MECATRONICS ENGINEERING Name of the project: Cardiovascular System Mock Circuit Name/Last Name of the Student: Emir Gkberk Eken Date of Thesis Defense: 06/07/2012

I hereby state that the graduation project prepared by Emir Gkberk Eken has been completed under my supervision. I accept this work as a Graduation Project. 06/07/2012 Dr. Kamuran Kadpaaolu

I hereby state that I have examined this graduation project by Emir Gkberk Eken which is accepted by his supervisor. This work is acceptable as a graduation project and the student is eligible to take the graduation project examination.

06/07/2012 Prof. Dr. Oktay ZCAN Head of the Department of Mechatronics Engineering

We hereby state that we have held the graduation examination of Your Name and agree that the student has satisfied all requirements. THE EXAMINATION COMMITTEE Committee Member 1. Dr. Kamuran Kadpaaolu 2. Prof. Erol Sezer 3. Dr. Khalid Abidi Signature .. .. ..

ACADEMIC HONESTY PLEDGE

In keeping with Baheehir University Student Code of Conduct, I pledge that this work is my own and that I have not received inappropriate assistance in its preparation.

I further declare that all resources in print or on the web are explicitly cited.

NAME Emir Gkberk Eken

DATE 06/07/2012

SIGNATURE

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ABSTRACT
CARDIOVASCULAR SYSTEM MOCK CIRCUIT Emir Gkberk Eken Faculty of Engineering Department Mechatronics Engineering Advisor: Dr. Kamuran Kadpaaolu JULY, 2012, 69 pages Heart disease is founded as the highest cause of death in the world. These loses can reduce by improving heart valves, ventricular assist devices (VADs), total artificial hearts, heart and lung machines etc. All these medical devices have to be tested on cardiovascular mock circuits (CVMCs) before starting clinical testing.

At 1975 Donovan et al. designed and built a complete mock circulation for testing artificial hearts but, atria or ventricles wasnt include to system. This CVMC has been the basis for many. Timms et al. (2010) designed and constructed a CVMC which includes both systemic and pulmonary circulatory systems. They accomplished to produce left ventricular pressure but, they couldnt prevent lagging in aortic pressure. Aortic valves opening and closing times or wrong resistance values may cause this problem. For prevent this problem more accurate heart valves may use and resistance may optimize with feedback control of proportional control valves.

Objective in this study was to design and build CVMC which is drivable with an elastance based feed-back control for simulate heart functions in various conditions. CVMC virtually designed by using Solidworks based on results which are obtained in the Simulink model. Pressure and flow inputs and check valve outputs are implemented into system by using dSPACE control card. CVMC operated successfully with compressed air and check valves. However, results are indicated a leaking problem of heart valves.

Key Words: Cardiovascular Mock Circuit, VAD and Heart valve test

ZET
CARDIOVASCULAR SYSTEM MOCK CIRCUIT Emir Gkberk Eken Mhendislik Fakltesi Mekatronik Mhendislii Blm Tez Danman: Dr. Kamuran Kadpaaolu TEMMUZ, 2012, 69 pages Kalp hastalklarndan kaynakl lmler hala dnyadaki en yksek saydaki lm sebebidir. Bu kayplar kalp kapakklar, ventrikl destek niteleri (VADs), yapay kalpler, kalp-akcier makinalar vs. Gelitirilerek azaltlabilir. Ancak btn bu aralar klinik testler ncesinde kardiovasculer mock dzenekleride (CVMC) test edilmelidir. Donovan ekibi 1975 ylnda kalp kapakklarnn denenmesi amacyla CVMC dizayn edip kurdular fakat, kulakk ve karncklar sisteme dahil edilmemiti. Bu sistem bir ok yenisi iin temel nitelii tamaktadr. 2010 ylnda Timms ve ekibi sistemic ve pulmoner taraflarn bulunduu bir CVMC dizayn edip kurdular. Bu sistemle sol karnck basncn baarl bir ekilkde elde etmelirne karn aort basncnn gecikmeli olarak elde edilmesini engelliyemediler. Bu probleme aort kapaknn zamannda alp kapanamamas yada diren deerlerinin optimum olmamas sebep olmu olabilir. Bu problemi engellemek iin daha iyi kalp kapakklar seilerek, direnlerde geri-besleme konroll, dorusal ak vanalaryla optimize edilebilinir. Kalp fonksiyonlarn eitli durumlara yerine getirebilicek, geri -beslemeli elastansla kontrol edilebilicek bir CVMC dizayn edip kurmak bu projenin amacdr. Bunun iin Matlabdeki simlasyonlardan elde edilen verilerle, SolidWorks de sanal dizayn yapld. Basn, ak bilgileri ve ek valflerini kontrolleri dSpace kontol borduna yerletirldi. CVMC hava basnc kullanlarak baarl birekilde iletildi. Ancak sorular kalp kaakklarnn kardna iaret etti. Anahtar Kelimeler: Kardiovasculer Mock dzenei, Kalp Kapak ve VAD test

vi

TABLE OF CONTENTS
ABSTRACT .......................................................................................................................... v ZET ................................................................................................................................... vi TABLE OF CONTENTS ....................................................................................................vii LIST OF FIGURES ............................................................................................................. ix LIST OF TABLES ..............................................................................................................xii LIST OF ABBREVIATIONS ............................................................................................xiii LIST OF SYMBOLS .......................................................................................................... xv I. INTRODUCTION ....................................................................................................... 1 1. Heart ..................................................................................................................... 1 1.1. Anatomy and Pathology of the Heart as a Pump ........................................ 1 1.2. The Cardiac Cycle ....................................................................................... 2 1.3. Frank Starling Mechanism ....................................................................... 4 1.4. Resistance .................................................................................................... 4 1.5. Compliance ................................................................................................. 5 1.6. Elastance ..................................................................................................... 5 1.8. Heart Disease .............................................................................................. 9 2. Mechanical Circulatory Assistance (MCA) ......................................................... 11 2.1. Left Ventricular Assist Devices (LVADs) ................................................ 11 2.2. Cardiovascular Mock Circuits (CVMCs) ................................................. 13 II. OBJECTIVES ............................................................................................................ 18 1. Desired Functions ................................................................................................ 18 2. Design Criteria ..................................................................................................... 18 III. MATERIALS and METHODS.................................................................................. 19 1. Cardiovascular Mock Circuit (CVMC) Simulation ........................................... 19 1.1. Aim ......................................................................................................... 19 1.2. Method.................................................................................................... 19

vii

1.3. Simulink Model ...................................................................................... 19 1.4. Design ..................................................................................................... 20 2. Cardiovascular Mock Circuit Virtual Design .................................................... 26 2.1. Aim ......................................................................................................... 26 2.2. Method.................................................................................................... 26 3. Cardiovascular Mock Circuit Mechanical Building .......................................... 28 3.1. Heart Valves ........................................................................................... 29 3.1.1. Heart Valve Selection .......................................................................... 29 3.1.2. Assembly of Heart Valves ................................................................... 29 3.2. Check Valves .......................................................................................... 30 3.3. Pressure Sensors ..................................................................................... 32 4. Cardiovascular Mock Circuit Control ................................................................ 34 4.1. Aim ......................................................................................................... 34 4.2. Method.................................................................................................... 34 4.3. Hardware Installation of dSPACE DS1104 ........................................... 34 4.4. Software Installation of Control Desk .................................................... 35 4.5. Software Installation of Matlab/Simulink .............................................. 36 IV. RESULTS .................................................................................................................. 41 1. LV and Ao Pressures ......................................................................................... 42 2. Left Ventricular Volume .................................................................................... 44 3. P-V Loop ............................................................................................................ 45 4. Elastance ............................................................................................................ 46 V. DISSCUSION & CONCLUSION ............................................................................. 47

VI. FUTURE WORK ....................................................................................................... 48 VII. APPENDIX A ............................................................................................................ 48 REFERENCES ................................................................................................................... 51

vii

LIST OF FIGURES
Figure 1- Structure of the heart, and course of blood flow through the heart chambers and heart valves ........................................................................................................................... 1 Figure 2- Events of the cardiac cycle for left ventricular function, showing changes in left atrial pressure, left ventricular pressure, aortic pressure and ventricular volume. .............. 3 Figure 3- Effect on the cardiac output (CO) curve of left atrial pressure (LAP) .................. 4 Figure 4- Pressure Flow relationship value references on the pipe ................................... 5 Figure 5- Elastance and Compliance in RV, LV and Ao at systole and diastole ................. 6 Figure 6- Volume-pressure diagram, demonstrating changes in volume and pressure during the normal cardiac cycle. ........................................................................................... 7 Figure 7- Pressure-Volume Loop and Elastance-Time Curve .............................................. 7 Figure 8- Ventricular Potential Enegry and Stroke Work Diagram ..................................... 8 Figure 9- Effect on the Demand Oxygen DO2 of pressure volume area (PVA) ................... 9 Figure 10- HeartMate II LVAD as Bridge to Transplant System in Patients Body ........... 11 Figure 11- Parameters of open air reservoirs in a single subsystem of CVMC model. ...... 16 Figure 12- Parameters of closed air reservoirs in a single subsystem of CVMC model. ... 16 Figure 13- CVMC chambers and connections to each other. ............................................. 19 Figure 14- Parameters of pneumatic cylinder in a single subsystem of CVMC model. ..... 20 Figure 15 - A schematic of open air reservoirs in a single subsystem of CVMC model.... 21 Figure 16- Matlab/Simulink result of open-air reservoir .................................................... 21 Figure 17- Figure 18 - A schematic of close air reservoirs in a single subsystem of CVMC model................................................................................................................................... 22 Figure 19- Simulation Result for Compliance of Aorta Chamber ...................................... 22 Figure 20- Pneumatic Check Valves Placement in Left Ventricual System ...................... 23 Figure 21- Sine function values with respect to time. ........................................................ 23 Figure 22- A Simulink schematic and sine wave function and saturation values of RV of CVMC model. ..................................................................................................................... 24 Figure 23- Result of RV pressure function designed on Simulink. .................................... 24 Figure 24- A Simulink schematic and sine wave function and saturation values of RV of CVMC model. ..................................................................................................................... 25 Figure 25- Result of LV pressure function designed on Simulink. .................................... 25

ix

Figure 26- A schematic of CVMC model. .......................................................................... 25 Figure 27- Left Ventricle Pneumatic System Design ......................................................... 26 Figure 28- Solidworks Drawing of Designed Chamber ..................................................... 27 Figure 29- Solidworks Design of CVMC. .......................................................................... 28 Figure 30- St. Jude Mechanical Heart Valve ...................................................................... 29 Figure 31- Assembly of Heart Valves ................................................................................ 29 Figure 32- Pneumatic Check Valve .................................................................................... 30 Figure 33- Technical Drawing of Pneumatic Check Valves .............................................. 30 Figure 34- Check Valves Relay Circuit .............................................................................. 31 Figure 35- a) Calmed Pressure Transducers for Aort and Left Ventricle b) Edwards Pressure Transducers for Pressure Tank ............................................................................. 32 Figure 36- PBV connector of Pressure Transducers ........................................................... 32 Figure 37- A Non-inverting Amplifier Circuit ................................................................... 32 Figure 38- Amplifier Circuit ............................................................................................... 33 Figure 39- DS1104 R&D Controller Board ........................................................................ 34 Figure 40- Single Board Hardware of DS1104................................................................... 35 Figure 41- Control Desk Example Screen .......................................................................... 35 Figure 42- Simulink Schematics of Pressure Transducers ................................................. 36 Figure 43- Transonic Systems HT110 Bypass Flow Meter Panel ...................................... 37 Figure 44- Transonic Systems Inc. Ultrasonic Flow Meter Sensor .................................... 37 Figure 45- Flow meter placement on Y-connector ............................................................. 38 Figure 46- Simulink Schematics of Flow Sensor ............................................................... 38 Figure 47- Simulink Schematics of Check Valves Controller ............................................ 39 Figure 48- Simulink Schematic of General Connection ..................................................... 39 Figure 49- dSPACE connections of pressure transducers, flow meter and check valves ... 40 Figure 50- Workspace, heart monitor, dSPACE board, Flow-meter panel, amplifiers and power-supply....................................................................................................................... 40 Figure 51- Built four chambers Mock circuit ..................................................................... 41 Figure 52- ControlDesk GUI .............................................................................................. 42 Figure 53- Ideal PLV, PAo with Time Graph ........................................................................ 42 Figure 54- Recorded LV and Ao Pressures ........................................................................ 43 Figure 55- Pressure Relationships in Aortic Insufficiency vii ............................................. 44

Figure 56- Ideal Left Ventricular Volume Change ............................................................. 44 Figure 57- LV Volume Change produced by CVMC ......................................................... 44 Figure 58- Ideal P-V Loop for Healty Human .................................................................... 45 Figure 59- Recorded P-V Loop of CVMC ......................................................................... 45 Figure 60- Mitral and Aortic Valve Regurgitation ............................................................ 45 Figure 61- Ideal Elastance Graph ....................................................................................... 46 Figure 62- Created Elastance Signal for P2......................................................................... 46

xi

LIST OF TABLES
Table 1- VAD devices, generations, manufacturers and types. .............................. 12

xii

LIST OF ABBREVIATIONS
ADC AHF Ao AV C CHF CO CVMC DAC GUI HF HR I/O IVC IVR LA LV MAP MCA MV PA PA PC PE PV PVA PVR RA RTI RV Analog to Digital Converter Acute Heart Failure Aorta Aortic Valve Compliance Chronic Heart Failure Cardiac Output Cardiovascular Mock Circuit Digital to Analog Converter Graphical User Interface Heart Failure Hearth Rate Input/output Isovolumetric or Isovolumic contraction Isovolumetric or Isovolumic relaxation Left Atrium Left Ventricle Mean Aortic Pressure Mechanical Circulatory Assistance Mitral Valve Pulmonary Artery Pulmonary Artery Pulmonary Capillary Potential Energy Pulmonary Venous Pressure Volume Area Pulmonary Vascular Resistance Right Atrium Real-time Interface Right Ventricle

xii

SAP SC SV SVR SW T TV VAD

Systolic Aortic Pressure Systemic Capillary Stroke Volume Systemic Vascular Resistance Stroke Work Cardiac Cycle Length Tricuspid Valve Ventricular Assist Device

xiv

LIST OF SYMBOLS
Units SI Conventional Pa mmHg m m cm m cm m cm m [dimensionless] [dimensionless] [dimensionless] [dimensionless] Pa.s N.s/m 3 m /s mL/min Pa.s/m mmHg.min/mL m/Pa m/mmHg Pa/m mmHg/mL

Symbol P V L r d Q R C E

Explanation Pressure Volume Length Radius Diameter Mathematical constant Difference Dynamic viscosity Volumetric flow rate Resistance (Hydraulic) Compliance Elastance

xv

I.

INTRODUCTION

1. Heart The heart can be considered as a pulsatile pump the duty of which is to receive blood from a low pressure reservoir and deliver it to high pressure reservoir at a given flow rate. Unidirectional characteristic of the fluid flow inside the pump is achieved with check valves.

1.1. Anatomy and Pathology of the Heart as a Pump Right atrium (RA) receives deoxygenated blood returning from the body via superior and inferior venae cava (See Figure 1). Blood flows into the right ventricle (RV) through, the tricuspid valve (TV). It is then pumped through the pulmonary valve into the pulmonary artery (PA). The PA splits into two to supply blood to both the left and right lungs, where the blood is oxygenated and flows into the left atrium (LA). Mitral valve (MV) opens and blood flows into the left ventricle (LV), where it is pumped through, the aortic valve (AV) into the aorta (Ao) at high pressure. Blood then flows through the high resistance systemic arteries and the low resistance systemic veins back to the RA. From this point, the circulatory cycle starts over to continually supply oxygenated blood to the whole body.

Figure 1- Structure of the heart, and course of blood flow through the heart chambers and heart valves 1

The circulation through the pulmonary arteries, capillaries and veins is realized by the RV and the circulation though the systemic arteries, capillaries and veins is realized by the LV. Since the total pulmonary resistance is almost five times lower than that of the total systemic resistance, the pressures are proportionally higher in the LV compared to RV in order to realize the same flow rate across each pump. This relationship can be expressed by the formula, ( ) ( ) ( )

(Eq. 1)

1.2. The Cardiac Cycle The cardiac cycle starts from the beginning of one heartbeat and ends at the beginning of the next heartbeat; and consists of four phases. Only the cycle in the LV will be explained below for simplicity, the cycle in the right heart being exactly the same, except for the differences in the names of the anatomic structures involved.

The first phase is called diastole. Diastole includes rapid inflow of blood into the LV from the LA through the MV, diastasis and atrial kick. Rapid inflow is caused when the ventricular pressure falls below the atrial pressure. As a result, the AV valve opens and blood flows into the ventricle rapidly as ventricular pressure keeps falling due to the continued relaxation of the ventricular wall. Diastasis is the period during which the heart is completely relaxed and the inflow rate is slowed down. . Towards the end of diastole, the atrium contracts, increasing the pressure inside and forcing the remaining blood into the ventricle. This is called the atrial kick.

The second phase of the cardiac cycle is isovolumetric (or isovolumic) contraction (IVC). As the ventricle contracts, the pressure inside the left ventricle (left ventricular pressure, PLV) rapidly increases and forces the closure of the mitral valve. LVP continues to rise until it reaches the level of the pressure inside the aorta (Aortic pressure, PAo). During this short period of rapid pressure rise, left ventricular volume (V LV) doesnt change because both AV and MV are closed. As soon as PLV surpasses PAo, AV opens, blood starts to flow into the aorta, VLV begins to drop and IVC ends.

The third phase is called systole. Systole consists of two parts. These are rapid ejection and deceleration. Rapid ejection occurs when pressure inside the ventricle becomes higher than the pressure of the aorta then aortic valve open and blood flows into the aorta. Ventricular pressure remains slightly higher than Aortic pressure in order to create flow (QLV) through the aortic valve resistance shown in (Eq. 1). However, volume of ventricle decreases rapidly. Reduced ejection occurs when aortic pressure just above that the ventricular pressure, but blood flows into Ao because of inertia of blood itself. The atrial pressure rises slowly during this phase.

The fourth and last phase is Isovolumetric relaxation (IVR), occurs when the ventricular pressure falls rapidly and aortic pressure become lower than below ventricular pressure and aortic valve closes (See Figure 22).

All phases listed for LV are also valid for RV.

Figure 2- Events of the cardiac cycle for left ventricular function, showing changes in left atrial pressure, left ventricular pressure, aortic pressure and ventricular volume.
1

1.3. Frank Starling Mechanism The Frank Starling law states that the heart has ability of increasing contraction force and as a result its stroke volume. The Frank Starling law states that as more blood is flowed into the ventricle, the heart works harder to pump more blood. The Frank Starling law also states that heart is a loop that doesnt leak blood and what goes into ventricle must come out.1 Cardiac Output formula is shown below;

(Eq. 2)

Figure 3- Effect on the cardiac output (CO) curve of left atrial pressure (LAP)

1.4. Resistance Hydraulic resistance in vessels is defined as the slope of the pressure-flow relationship obtained by measuring vascular pressure at several fluid flow rates 2.

It is determined by the length (L), cross-section area of the pipe and fluid viscosity( ). Cross-section area calculates by using diameter (d) or radius (r). In standard fluid dynamics notation 3 (See Figure 4 ).

(Eq. 3)

Figure 4- Pressure Flow relationship value references on the pipe

1.5. Compliance Compliance (C) is the unit change in volume (V) of a deformable reservoir under unit change in pressure (P) applied into the reservoir. Also compliance is a passive property of the reservoir. It is given by the formula,

(Eq. 4)

1.6. Elastance The inverse of the compliance, the elastance is an active property. Elastance (E) describes the dynamics of the active return to the original shape of the variable volume reservoir after being passively filled. E is given by the formula,

(Eq. 5)

In the context of CV hemodynamics, C is used to describe the elastic properties of the atria, ventricles, arteries and veins under internal filling pressures.

E, on the other hand, is used to define the active internal contractile power of the ventricle during systole; or the strength with which major elastic-walled arteries, (especially Ao and PA) after being distended with systolic blood, squeeze passively and create internal pressure to propel blood forward during diastole.

Figure 5- Elastance and Compliance in RV, LV and Ao at systole and diastole

1.7. Pressure Volume Loop The physiologic meaning of cardiac phases, compliance and elastance can be better observed in the content of the pressure volume loops. Pressure-volume diagram shows simultaneous changes in volume and pressure during the cardiac cycle for the left ventricle. It consists of four phases, which are the same as those explained previously in section 1.2.

Phase I: Filling period (diastole). This phase starts the mitral valve opens, a ventricular pressure value around 0 and volume is about 45-50 milliliters and it called the end-systolic volume. Blood flows into left ventricle from the left atrium. Left ventricle pressure (PLV) and volume (VLV) increase to about 115-120 milliliters and 5 mmHg, respectively end-diastolic volume and pressure.

Phase II: Isovolumetric contraction period. This phase begins when the mitral valve closes upon the rise of PLV, while the aortic valve stays closed. During contraction the volume of the left ventricle doesnt change as both AV and MV are closed, so this phase called Isovolumetric contraction. On the other hand, pressure in the left ventricle increases rapidly until pressure of the left ventricle equals the Aortic pressure (P Ao) at about 80 mmHg.

Phase III: Ejection period (systole). This phase begins when the aortic valve opened. Blood flows into the aorta from left ventricle. During the ejection, pressure continues rising because of ventricle still contracts. At the same time the left ventricle volume decreases because of contraction. 6

Phase IV: Isovolumetric relaxation period. This phase begins when the aortic valve is closed and the mitral valve is closed. The left ventricle pressure falls back to the diastolic pressure level. During relaxation the volume of the left ventricle doesnt change, so this phase called Isovolumetric relaxation. ( ) ( ) ( ) (Eq. 6)

Figure 6- Volume-pressure diagram, demonstrating changes in volume and pressure during the normal cardiac cycle.

Elastance based control uses curve shown at Figure 7 . It is only experimentally derived. No method to accurately describe how it is performed.

Figure 7- Pressure-Volume Loop and Elastance-Time Curve

)(

) (Eq. 7)

(Eq. 8)

Figure 8- Ventricular Potential Enegry and Stroke Work Diagram

) (Eq. 9)

Myocardial oxygen demand ( (PVA). As shown in the formula.

) is a function of the pressure volume area

(Eq. 10)

In formula, 2.46 is a dimensionless variable find from given formula; 4

means energy needed for hearts basal metabolism and PVA. (see Figure 9) 8

doesnt dependent on

Figure 9- Effect on the Demand Oxygen DO2 of pressure volume area (PVA)

1.8. Heart Disease When the pumping function of the heart is not enough to provide the necessary flow to the body at the required pressure, the pump is said to fail. National Institute for Clinical Excellence defines heart failure as a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation.i

Acute heart failure (AHF) is defined as the rapid or progressive beginning of symptoms of heart failure AHF can be often cured with treatment.5 Chronic heart failure (CHF) is a long-term condition, heart muscle cant eject required amount of blood out of the heart over an extended period, e.g. months to years. This is called systolic chronic heart failure. If heart muscles are stiff and doesnt fill up with blood (diastole), this is called diastolic chronic heart failure.6

End Stage heart disease is the final outcome of many forms of heart disease that progressed to an end stage or an advanced form of that disease. The heart can no longer pump enough blood to fulfill the body's metabolic requirements. 6
i

National Institute for Clinical Excellence Chronic heart failure Management of chronic heart failure in adults in primary and secondary 2003 care. London

Coronary heart disease causes the death of more than 2 million people in European Union and 5.3 million people in Europe each year by being most important effect in all death reasons. %50 of coronary heart disease death occurs before age 75 and %15 occurs before age 65 in Europe.ii

Moreover, 5.2 million adults between ages 40 to 70 year of age in USA have heart failure and every year 550.000 new cases occur. 1 million of these patients have periodic heart attacks and half of these patients die in one year. According to the 2002 World Health Organization Report, 11.8% of males and 10.5% of females in the world population had troubles from heart disease. High death risk of heart disease, in 2002, 16,655,000 people died in the world.iii National Vital Statistic Report in the USA shows that 831,000 people died from various forms of heart diseases in 2006 and, in 56,565 the cause of death was heart failure.iv

ii

Annual Report 2009 by European Hearth Network The World Health Report 2003: Shaping the Future. World Health Organization. iv National Vital Statistics Reports, Deaths: Final Data for 2006. U.S. Department Of Health And Human Services
iii

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2. Mechanical Circulatory Assistance (MCA)

Heart pumps were invented in order to keep alive CHF patients until heart transplantation. However, donated organs are limited, but the number of patients waiting for a heart transplant waiting is increasing with the population. Because of that, heart pumps were designed that can implanted by providing options for patients on whom transplantation operation cant be performed (Bridge to Transplant). So, patients started to live with portable mechanical cardiovascular circulation assistances (MCA) until transplantation. LVAD is a heart pump that is Bridge to Transplant system by pumping blood from Left Ventricle to Aorta (See Figure 10).

Figure 10- HeartMate II LVAD as Bridge to Transplant System in Patients Body 7

2.1. Left Ventricular Assist Devices (LVADs) The left ventricular assist device (LVAD) is a mechanical pump which is implanted to help the hearts left ventricle pump blood into the aorta. LVADs are used in patients with end-stage heart failure.

The early VADs replicated the heart by using a "pulsatile" action where blood is alternately sucked into the pump from the left ventricle then forced out into the aorta.

Continuous flow pumps have the advantage of simplicity resulting in smaller size and higher safety. These devices are referred to as second generation LVADs. A side effect is that the user will not have a pulse or that the pulse intensity will be seriously reduced. These are second generation LVADs. 11

Third generation LVADs removed bearings in the pump using either hydrodynamic or electromagnetic suspension or both together, and reducing the number of moving parts to one.

Device

Generation Generation 1 Generation 1 Generation 2 Generation 2 Generation 2 Generation 2 Generation 3 Generation 3 Generation 3

Manufacturer

Type Pulsatile. Pulsatile. Continuous axial flow Continuous axial flow Continuous axial flow Continuous axial flow Continuous centrifugal flow Continuous centrifugal flow Continuous centrifugal flow

Novacor HeartMate XVE HeartMate II

HeartMate III

World Heart Thoratec Thoratec Thoratec Jarvik Heart MicroMed

Ventracor

Jarvik 2000 MicroMed DeBakey VAD

VentrAssist

HVAD DuraHeart

HeartWare Terumo

Table 1- VAD devices, generations, manufacturers and types.

Sha Kkaksu et al. placed three MicroMed DeBakey VAD to three male patients, aged 37, 41 and 40, all had end-stage left heart failure. These are the 1st implantations of a left ventricular assist device in Turkey. 8

Producing this LVAD in Turkey has some advantages. Because people who will use LVAD can attend stages for medical opinion of designing and producing of LVAD, the rate of deaths caused by using imported LVADs in a wrong way will decrease. For testing LVAD before humans it has to be tested on Cardiovascular Mock Circuits (CVMCs) and animals.

12

2.2. Cardiovascular Mock Circuits (CVMCs) CVMCs are used as a mechanical representation of human cardiovascular system in vitro. Early versions of CVMCs were built for testing artificial heart valves CVMCs also can be used for testing of total artificial hearts, artificial lungs and many other artificial organs. In these systems stepping motors used for create an artificial heart beat.9
10

Kolff et al. (1959)

constructed a mock circuit which consisted of both

pulmonary and systemic sides. Compressed air used to operate ventricles, also to obtain pressures of aortic and pulmonary arterial chambers. No resistance valves used in this study.

Donovan et al. (1975)

11

designed and built a complete mock circulation for

testing new artificial heart designs in an artificial environment. However, Donovan et al didnt include atria or ventricles which limit the cardiovascular device testing capabilities. This device used acrylic material to build a chamber, for replicate aortic, systemic venous, pulmonary arterial, pulmonary venous and ventricular components. Dimensions of this system are 605mm wide, 403mm high and 202mm deep. This cardiovascular mock circuit has been the basis for many CVMCs since.

Verdonck et al. (1992)

12

designed and built a complete mock circulation for

testing mitral valves. For this reason aortic and mitral valves in the system could change easily. The left ventricle verb made by silicone and latex atrium were both anatomically shaped and mounted in water filled Plexiglas tanks where the pressures are controlled by an external circuit. This CVMC was later used by Vandenberghe et al. in 2003, to estimate the hydrodynamic performance of the PUCA II LVAD. 13

Baloa et al. (2001)

14

studied control of cardiovascular mock circuit by using the

elastance-based control. This study used the elastance of the ventricle to change control output and develop a new strategy. The authors concluded that this design was successful in using elastance-based control for simulating different cardiac conditions.

13

Koenig et al. (2004) 15 produced a systemic mock circulation to test pulsatile and continuous ventricular assist devices (VADs). A mock ventricle was created of

ellipsoid shape with mounts for the aortic and mitral valves. This system was used with a pressure chamber to replicate desired pressure values. A resistance realized by a latex tube in the system. However, the pulmonary circulation to complement the systemic side was not included in the system.
16

Pantalos et al. (2004)

constructed a CVMC to replicate the Frank Starling

response for several situations. In this system flexible polyurethane was used for produce atrium and ventricle. A polyurethane aorta was connected to the ventricle. Pressure volume loops representing natural situations were produced also this system can be replicate the Frank Starling response for all situations. The primary limitation of this system is there is not having a pulmonary vasculature mock circulatory system.
17

Gregory S.D. (2004)

designed a mock circuit that used compliance based

control. Means calculating pressure using compliance. Also Mock Circuit didnt accurately replicate the elastic nature of pressure and volume values in Figure 2. Timms et al. (2005) 18 designed and constructed a complete CVMC for testing of VADs. The purpose of this study was to design and construct a CVMC that was capable of replicating several situations. This mock loop was not shown to produce accurate pressure and flow data for several situations. Limitations in this study

involve the use of slow check valves for use in replacing the natural heart valves.
19

Timms et al. (2010)

designed and constructed a CVMC which includes both

systemic and pulmonary circulatory systems. Also simulation includes calculations of circuit volumes, resistances, and compliances. However, the system was not

accurately replicating the human cardiovascular system. There is a lagging between pressures of LV and Ao. Aortic valves opening and closing times may cause this problem.

14

In CVMCs, Air/water tanks (chambers) are used to model the venous and arterial compliances and venous, arterial, and other system ow resistances. Water is used instead of blood. Pressures are generated by water in hydraulic columns. Pressure is calculated with water height (h) in these columns, density (p) of water and acceleration of gravity (g) by given the formula, (Eq. 11) (Eq. 12) (Eq. 13) (Eq. 14)
v

(Eq. 15) (Eq. 16) (Eq. 17) ( ) (Eq. 18) (Eq. 19) ( ) (Eq. 20)

1st order kinematics exponential decay charge.

Ch: Hydrolic compliance.

15

Figure 11- Parameters of open air reservoirs in a single subsystem of CVMC model.

A r r (r- )(- )

(Eq. 21) (Eq. 22) (Eq. 23) (Eq. 24)

(Eq. 25) (Eq. 26) (Eq. 27) ( ( ) ) (Eq. 28)

Figure 12- Parameters of closed air reservoirs in a single subsystem of CVMC model.

16

17

II.

OBJECTIVES

1. Desired Functions Goal of this project is to design and build Cardiovascular Mock Circuit which is drivable with an elastance based feed-back control that can replicate hearts pressure-volume relationship accurately. For this goal pressure volume relationship was calculated using elastance.

Product of this project will be used for VADs tests for this purpose product must be sturdy. Product life has to be at least 5 years. However, product has also to be cheap either. On the other hand system must be accurate for trustable test results. That means system has to reproduce values of pressure, volume, flow of cardiovascular system within 5% error of pressure and flow values. Modularity is another function desired for CVMC. System has to allow for later improvements. Control of CVMC system has to be elastance based feed-back control for reducing errors.

2. Design Criteria Product life depends on material selection and design of parts. In order to choose material, all of the criteria have to take into account. Body of chambers must be transparent and rigid. Piston, top and bottom covers must be though, rigid and strong and leak-proof. Low cost Materials have to be chosen. However, this criterion conflicts to first criteria about transparency, rigidity and strength. In order to make an accurate model and getting an accurate aortic pressure and flow graphs, designing the right mechanical model is important. The mechanical design must be compatible with both electrical and hydro-dynamical model of our vascular system. For modularity, design of parts has to be simple, replaceable and standardized as much as possible. Elastance based control requires simultaneously and continuously pressure and flow sensor inputs. Feed-back control changes output according to inputs, elastance and feed-back signal. 18

III.

MATERIALS and METHODS

1. Cardiovascular Mock Circuit (CVMC) Simulation

1.1. Aim Create a simulation model to replicate the function of the heart. This was to be used to design and improve CVMC by finding dimensions of mock circuit components such as length and diameters of pipe for suitable resistance or height and diameters of chambers. 1.2. Method Computer program called MATLAB/ SIMULINK (The Mathworks, Natick, MA, U.S.A) was chosen to simulate CVMC in visual environment.

1.3. Simulink Model A Simulink model was needed to simulate the functions and components of the CVMC. Components of the CVMC are shown in the (Figure 13).

Figure 13- CVMC chambers and connections to each other.

19

1.4. Design

There are eight chambers for simulating different parts of cardiovascular system. These are Venus Pool and Right Atrium (RA), Systemic Capillary (SC), Aorta (Ao), Left Ventricle (LV), Pulmonary Venous (PV), Pulmonary Capillary (PC), Pulmonary Artery (PA) and Right Ventricle (RV).

In the Left and Right Ventricles, simulated by pneumatic cylinders and generate pressure and volume. These cylinders have to supply maximum pressure, in the limitation of volume change.

Figure 14- Parameters of pneumatic cylinder in a single subsystem of CVMC model.

Six chambers of mock circuit are open to air, except Aorta which is the only chamber close to atmosphere. Because of high pressure of Aorta chamber if it is open air, it has to be high about 2 meters. Instead of using 2 meters high chamber, water height can be reduced by using close chamber with pressurized air above the water column.

To model the CVMC, subsystems for left atrium (LA), left ventricle (LV), aorta (Ao), systemic capillaries (SC), right atrium (RA), right ventricle (RV) and pulmonary arterial system (PA) were created. The pressure and flow output of each system was 20

calculated using the flow output from the previous subsystem and the pressure output from the following subsystem. A schematic of CVMC model can be seen in Figure 19. Parameters of a single subsystem for open air reservoirs which are LA, SC, RA, PA and Lungs, were shown in the Figure 15.

Figure 15 - A schematic of open air reservoirs in a single subsystem of CVMC model.

Figure 16- Matlab/Simulink result of open-air reservoir

21

Figure 17- Figure 18 - A schematic of close air reservoirs in a single subsystem of CVMC model.

1.2

x 10

-5

0.8

0.6

0.4

0.2

0 -2

-1.5

-1

-0.5

0.5

1.5

Figure 19- Simulation Result for Compliance of Aorta Chamber

Resistance has to be replicated by mock circuit. Also Systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) can change with a control valve to desired resistance level. 22

For create a ventricular pressure, sine wave function used and signal saturated. RV pressure changes between 5 mmHg to 25 mmHg. Also systole and diastole times are known.

Figure 20- Pneumatic Check Valves Placement in Left Ventricual System

Pneumatic valves and controlled LV pressure so that,

Constant In systole: ( and, in diastole: ( ) { ( ) ( ( ) ) ) { ( )( ( ) )

Figure 21- Sine function values with respect to time.

23

( ( ) ( ( ) (

( ) (

( ))

(Eq. 29)
) ( ))

( ) (

(Eq. 30)
) )

(Eq. 31) (Eq. 32)

Figure 22- A Simulink schematic and sine wave function and saturation values of RV of CVMC model.

Figure 23- Result of RV pressure function designed on Simulink.

24

Figure 24- A Simulink schematic and sine wave function and saturation values of RV of CVMC model.

Figure 25- Result of LV pressure function designed on Simulink.

Figure 26- A schematic of CVMC model.

25

2. Cardiovascular Mock Circuit Virtual Design

2.1. Aim By using the results obtained in the Simulink model of a Cardiovascular Mock Circuit (CVMC), a new CVMC was virtually designed to produce accurate pressure and flow diagrams. The new CVMC was required to replicate the human circulatory system.

2.2. Method SolidWorks (Dassault Systmes, Vlizy, France) is 3D CAD (Computer Aided Design) program is used to design the product before production. SolidWorks was used to design six air/water chambers and chamber for left ventricle (LV) and right ventricle (RV).

2.2.1. The Ventricle

Figure 27- Left Ventricle Pneumatic System Design

26

2.2.2. The Chamber

The six chambers which are Venus Pool and Right Atrium (RA), Systemic Capillary (SC), Aorta (Ao), Pulmonary Venous (PV), Pulmonary Capillary (PC) and Pulmonary Artery (PA) represented by transparent, horizontal chambers with one hole at the top for air transfer and three holes at the bottom of the chamber for fluid flow. Connection between chambers was provided by using flexible transparent Tygon tubes.

Figure 28- Solidworks Drawing of Designed Chamber

27

3. Cardiovascular Mock Circuit Mechanical Building

By using the results obtained in the Simulink model and Solidworks drawings of a Cardiovascular Mock Circuit (CVMC), a new CVMC was mechanically built to produce accurate pressure and flow diagrams. The new CVMC was required to replicate the human circulatory system.

CVMC is designed with four chambers for simplify system. However, this system can improve to eight chamber with adding other chambers.

Figure 29- Solidworks Design of CVMC.

28

3.1. Heart Valves 3.1.1. Heart Valve Selection For simulate heart valves St. Jude artificial heart valves was used. St. Jude mechanical heart valve is shown in the Figure 30. Both Aortic and Mitral valves are standard cuff-polyester types. Aortic valve (AV) tissue annulus diameter is 29 mm, Mitral valve (MV) tissue annulus diameter is 25 mm, and material is pyrolytic carbon and woven polyester cuff.vi

Figure 30- St. Jude Mechanical Heart Valve

3.1.2. Assembly of Heart Valves Artificial heart valves are placed into polypropylene tubes. In that way mitral valve is connected between LA and LV and Aortic valve is connected between LV and Ao. (see Figure 31 )

Figure 31- Assembly of Heart Valves

vi

St. Jude Medical Heart Valve Division, St Jude Medical Mechanical Heart Valve, Physicians Manual

29

3.2. Check Valves Pneumatic check valves are used for control air flow in the LV system. Check valves needs air pressure and +24V to change status. However, for

Figure 32- Pneumatic Check Valve

Figure 33- Technical Drawing of Pneumatic Check Valves

Diastole valve, systole valve and compression valve which are shown in Figure 20, were 30

used as three pneumatic check valves in shown positions.

Figure 34- Check Valves Relay Circuit

31

3.3.

Pressure Sensors

a)

b)

Figure 35- a) Calmed Pressure Transducers for Aort and Left Ventricle b) Edwards Pressure Transducers for Pressure Tank

Figure 36- PBV connector of Pressure Transducers

Range of data voltages are measured from pressure transducers are between 0 and 5mV. Thats why voltage amplified with analog amplifiers. As a amplifier Texas Instruments uA747C is used. Calculations of amplifier based on ideal pop-amp formula in (Eq. 33). Amplified voltage has to be between -10V and +10V for usability in the system and also protection of dSPACE hardware.

Figure 37- A Non-inverting Amplifier Circuit

32

(Eq. 33)

Amplifier circuit (shown in Figure 38) is constructed for each pressure transducer and output voltage is measured between 0V and +6.7V.

Figure 38- Amplifier Circuit

33

4. Cardiovascular Mock Circuit Control

4.1. Aim CVMC requires a control mechanism. It was vital that the parameters which control the CVMC could be easily changed.

4.2. Method dSPACE (dSPACE GmbH, Germany) is a hardware and software package that

supports the tools for control of check valves by collected real-time pressure and flow data from transduces and flow-meter.

4.3. Hardware Installation of dSPACE DS1104 dSPACE DS1104 R&D Controller Board upgrades PC to a powerful development system for rapid control prototyping (shown in Figure 39). Real-Time Interface (RTI) provides Simulink blocks for graphical I/O configuration. Controller board provides to configure all I/O graphically, insert the blocks into a Simulink block diagram, and generate the model code via Simulink.

Figure 39- DS1104 R&D Controller Board

dSPACE DS1104 Single-Board-Hardware has 8 analog to digital converters (ADC), 8 digital to analog converts (DAC), Digital I/O sub-d connector and serial interfaces. ADCs are used as input connections from pressure transducers and flow-meter. DACs are used as output connections from Matlab/Simulink to check valves. 34

Figure 40- Single Board Hardware of DS1104

4.4. Software Installation of Control Desk For the graphical user interface (GUI) Control Desk software was used (shown in the Figure 41). Control Desk allow user to change parameters in real time and reading input and output values simultaneously. Also Control Desk provides data accusation.

Figure 41- Control Desk Example Screen

35

4.5. Software Installation of Matlab/Simulink Simulink is a subprogram Matlab which is using of graphical block approach on computing environment. dSPACE software includes Simulink blocks which are designed for take inputs from CVMC via dSPACE to Simulink environment and gives outputs from Simulink to CVMC.

4.5.1. Pressure Input Pressure input is obtained from using analog amplified pressure signal in dSPACE. Two different kinds of pressure transducers are used. Calmed pressure transducers are used for measure Ao and LV pressures and Edwards pressure transducer is used measure for air tank pressure in CVMC. In dSPACE analog amplified pressure signal amplified digitally by 10 times because of dSPACEs ADC inputs reduces signal by 10 times for circuit protection. Digital pressure signal is filtered by Analog Filter Design box of Simulink for reduce noise and increase stability. Voltage of digital pressure signal measured and mapped by dSPACE. Measured data is compared with Drager heart monitor, as taken as golden standard of measurement, by using MATLAB, curve fitting function and quadratic polynomial method. After mapping results are rounded and pressure values are obtained (see Figure 42).

Figure 42- Simulink Schematics of Pressure Transducers

36

4.5.2. Flow and Volume Input Analog flow data is obtained by using Transonic Systems Inc. HT110 bypass flow meter panel (see Figure 43) and Transonic Systems Inc. ultrasonic flow meter sensor (see Figure 44). Analog signal output of flow meter is transferred from analog output of HT110 bypass flow meter panel to computer environment via dSPACE.

Figure 43- Transonic Systems HT110 Bypass Flow Meter Panel

Figure 44- Transonic Systems Inc. Ultrasonic Flow Meter Sensor

37

Digital data which is measured by dSPACE compared with flow values which are read from HT110 Bypass Flow Meter Panel. MATLAB, curve fitting function, linear polynomial method is used for determine gain between flow value and digital flow data. Flow value is obtained as a L/min unit and converted to ml/sec (SI unit) by conversion gain. For finding volume value in chamber, flow value is integrated and summed with a initial volume.

Figure 45- Flow meter placement on Y-connector

Figure 46- Simulink Schematics of Flow Sensor

38

4.5.3. Check Valve Control Check valves are control by pulse signal generators. Opening time and duration are adjusted by hand. Changing timing of these time variables is provided to change diastole and systole duration, heart rate, elastance and stroke volume.

Figure 47- Simulink Schematics of Check Valves Controller

4.5.4. General Connection Flow sensor, pressure transducers and check valves connected to each other as shown in Figure 48.

Figure 48- Simulink Schematic of General Connection

39

Figure 49- dSPACE connections of pressure transducers, flow meter and check valves

Figure 50- Workspace, heart monitor, dSPACE board, Flow-meter panel, amplifiers and power-supply.

4.5.5. CONTROLDESK Graphic Based User Interface (GUI) CONTROLDESK provides a graphic based user interface (GUI) for observe Simulink system in real-time. CONTROLDESK is used for observe LV and Ao pressure, P-V loop, elastance control signal and other control parameters. 40

IV.

RESULTS
All result are obtained by using CVMC built in Bahcesehir University, Bioengineering Research Laborotory. Four chamber CVMC shown in the Figure 51.

Figure 51- Built four chambers Mock circuit

41

Figure 52- ControlDesk GUI

The CVMC is successfuly replicated heart physiology in vitro. Pressure values of LV and Ao and LV volume values conditions stably and accurately. are verifed the abiliy of CVMC regenerate physical

First part of the ControlDesk/GUI (Figure 52) shows PLV (Green line) and PAo (Red line) which are obtained by Calmed pressure transducers via dSPACE. Second part shows P-V loop of heart, x axis is indicated LV volume and y axis is indicated LV pressure, in real-time. In third part in an order PLV, PAo, air-tank pressure and LV volume are numerically showed. At the bottom of the screen elastance based air-tank pressure and LV volume are showed by graphically.

1. LV and Ao Pressures

Figure 53- Ideal PLV, PAo with Time Graph

42

PLV and PAo values recorded in real time and grafically displayed in Figure 54. In all results maximum pressures are slightly elevated from 120 mmHg to 130-140 mmHg. However, pressures can reduce by decreasing maximum air-tank pressure, means decreasing elastance.

A)

B)

C)
Figure 54- Recorded LV and Ao Pressures

As you can see from Figure 54 PAo increases before AV open and also PAo decreases rapidly after AV close. These results indicate AV leaking when it is closed. The presence of backwards flow across a closed cardiac valve is defined as valvular regurgitation (insufficiency).vii In this project there is Aortic insufficiency and results are supported this finding. (See Figure 55)

vii

Web source: ` Doppler Changes in Valvular Regurgitation` http://www.echoincontext.com/doppler02/doppler02_02.asp

43

Figure 55- Pressure Relationships in Aortic Insufficiency vii

2. Left Ventricular Volume Ideal volume is shown in the Figure 56. Stroke volume (V) in human normal physiology is approximately 70-80 ml. However, in ideal pressures CVMC produces less stroke volume than ideal (See Figure 57). That mean resistance between LV and Ao is higher than human physiology.

Figure 56- Ideal Left Ventricular Volume Change

Figure 57- LV Volume Change produced by CVMC

44

3.

P-V Loop

III P-V Loop Stages II I I -Diastole II -IVC III -Systole IV -IVR

Figure 58- Ideal P-V Loop for Healty Human

IV

A)

B)

C)

Figure 59- Recorded P-V Loop of CVMC

Ideal P-V loop for healthy human is shown in the Figure 58 and some of the recorded p-v loops shown in the Figure 59. As you can see in the recorded p-v loops IVC and IVR are not completely isovolumetric that results supports the theory about heart regurgitation (see Figure 60). Also stroke volume is not sufficient but in the Figure 59, C stroke volume is in an acceptable range.

Figure 60- Mitral and Aortic Valve Regurgitation viii

viii

Web Source: Aortic and Mitral Regurgitation http://www.cvphysiology.com/Heart%20Disease/

45

4. Elastance

Figure 61- Ideal Elastance Graph

In CVMC, elastance is directly proportional to P2 (LV air pressure, see Figure 20). That is the reason control algorithm based on controlling P2.

Figure 62- Created Elastance Signal for P2

46

V.

DISSCUSION & CONCLUSION

CVMC has been designed to replicate pumping functions of heart and characteristics of circulatory system.

Cardiovascular mock circulation systems provide an easy and desirable way for testing cardiac devices during development process. For this reason system has to be portable, adjustable and most importantly trustable.

Recreate heart pumping function with controlling compressed air in the ventricle was successful. Results are comparable to heart functions but, system has to simulate different heart states and failure situations.

The shapes of the PV loops which are obtained with CVMC were similar to in vivo results. However, an increasing in volume was observed at the beginning of diastole and the end of the systole. The problem is artificial heart valves (AV- MV) are leaking when they are closed. This problem gives similar results with Aortic insufficiency.

47

VI.

FUTURE WORK
In my master thesis I am planning to improve CVMC. Heart Valves will change with hydraulic check valves because of static leaking during IVR and IVC. Air check valves will change with proportional control valves for control air pressure increase and decrease durations. Resistances will change with computer controlled proportional control valves for simulate different conditions and diseases of heart and circulatory system. RV and other chambers will add to CVMC. For new chambers and RV, new pressure and flow sensors will implement to the system. New ventricle design will be build and implement into system. (see Appendix A)

VII.

APPENDIX A

48

49

50

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