Final Report Development of a Pulsatile Left Heart Simulator

Transcription

1 0 Final Report Development of a Pulsatile Left Heart Simulator Stephanie Bendtsen, Joseph Calderan, Celeste Dupont Team #17 Client #25 Client Contact: Dr. Wei Sun, University of Connecticut Tissue Mechanics Lab, 260 Glenbrook Road, Unit 2247, Storrs, CT 06269, (860)

2 1 Contents Abstract Introduction Background Purpose of Project Previous Work Done by Others Products Patent Search Results Map for the Rest of the Report Project Design Introduction Alternative Design Alternative Design Alternative Design Optimal Design Objective Subunits Prototype Realistic Constraints Engineering Standards Economic Constraints Environmental Constraints Sustainability Manufacturability Health and Safety Constraints Social Constraints Safety Issues Impact of Engineering Solutions Life-Long Learning Budget Team Members Contributions to the Project Stephanie Bendtsen Joseph Calderan... 25

3 2 8.3 Celeste Dupont Conclusion References Acknowledgements Appendix Updated Specifications Technical Specifications Material Specifications... 28

4 3 Abstract The purpose of this design project is to develop a pulsatile left heart simulator that tests mechanical and bioprosthetic replacement heart valves while accurately simulating the natural pressure and fluid flow conditions of the heart. The client requested that we improve the current flow loop design in his tissue mechanics laboratory, as well as design a method for easy implementation of a biological aortic root into the aortic valve position. In addition, he requested that we include camera ports that will allow clear images of the replacement valves to be obtained from both inlet and outlet sides during testing. To fulfill his requests, we developed a flow loop design oriented horizontally that includes simulations of the major components of the left side of the heart. The fluid flow begins at the atrium and flows through the mitral valve to the ventricular chamber. It is then pumped at a right angle through the aortic valve out to the ascending aorta, compliance chambers, and throttle valve before returning to the atrium. Viewing ports are present on both sides of the ventricle to obtain the desired images of the mitral and aortic valves during testing. Through the use of a flow meter and pressure sensors located throughout the system, physiological cardiac waveforms are obtained as a result of each test. Because the replacement valves have already been bench marked in previous tests in Dr. Sun s laboratory, we compared our results to those already obtained to ensure that our flow loop functions properly. Research and tests of replacement heart valves are both crucial to the implementation of replacement heart valves in patients with heart valve disease. Although a few devices have been developed in this area of research, our pulsatile flow loop design provides an innovative way to further enhance replacement heart valve testing methods. 1 Introduction 1.1 Background The client, Dr. Wei Sun, is an assistant professor in mechanical and biomedical engineering at the University of Connecticut. He has engaged in research focusing on cardiovascular biomaterials and biomechanics of replacement heart valves. Dr. Sun s old pulsatile left heart simulator reproduces appropriate physiological cardiovascular waveforms at each phase of the cardiac cycle. However, the goal is to alter the flow loop design so that the model is horizontal and easier to use, yet still reproduces the proper waveforms. The new system includes a more efficient way to mount the valves and has more secure valve housing. It accommodates for mechanical and bioprosthetic valve replacements of various sizes. Also, videos and images of the mitral and aortic valves can be obtainable from both sides of the system. 1.2 Purpose of Project The American Heart Association has reported that about five million Americans are diagnosed with heart valve disease each year. Heart valve disease is loosely defined as the condition in which one or more heart valves do not function properly. Valvular stenosis and valvular insufficiency are two types of valve dysfunctions. Valvular stenosis occurs when the valve tissue is so stiff that it prevents the valve from opening fully. This requires the heart to

5 4 work harder to pump blood through the valve, and may be attributed to aging or various infections. Valvular insufficiency is defined as an inefficient blood circulation through the heart, resulting in regurgitation. This condition is known as having a leaky valve because the valve does not close tightly as it should, which allows the blood to regurgitate, or leak backwards. For example, mitral regurgitation allows blood from the left ventricle to flow back into the left atrium. As a consequence of this improper valve function, less blood flows to the rest of the body. Both of these conditions are very serious and may even lead to death if left untreated. [1] Heart valve replacement surgery is one effective solution to the various problems accompanying heart valve disease. In this procedure, a mechanical or bioprosthetic heart valve is implanted into the heart in place of the defective valve. This design project serves to test heart valve replacements previously benchmarked in Dr. Sun s lab and to ensure that they function properly. The pulsatile flow loop simulates and recreates the pressure and flow conditions that exist in the left side of the heart. The modified design more accurately represents the natural working conditions of the cardiac cycle by allowing implementation of a biological aortic root into the flow loop while maintaining the accurate pressure and physiological cardiac waveforms. The model also includes windows on both sides of the ventricle so that images and videos can be taken of the mitral and aortic valves functioning during testing. These pictures and videos can then be studied, and necessary adjustments of the valves will be apparent. It was important to improve the previous pulsatile flow loop because the data obtained from this new system will give insight as to whether or not the replacement valves are functioning properly and can be implemented into human patients suffering from heart valve disease. Many individuals rely on suitable heart valves replacements to improve their quality of life. Proper functioning of the heart valves is crucial because if they are not studied and FDA tested, valve failure can result in death of the patient. 1.3 Previous Work Done by Others Products ViVitro Labs Inc. in Canada has developed the ViVitro Pulse Duplicator. This pulsatile heart simulator tests the performance and function of various heart valve replacements. In addition to testing mechanical and bioprosthetic valves, the Pulse Duplicator permits the testing of percutaneous, venous, and stented tissue valves. An image of the device is shown in Fig. 1. It is powered by a piston-in-cylinder pump head with a digital motor having a high torque to inertia ratio. As a brief overview of the model, the systematic set-up includes an atrium chamber which houses the mitral valve, leading to the ventricle. From the ventricle, the aortic valve leads out to compliance chambers via tubing. Tubing also connects the compliance chambers to a throttle valve serving as resistance, and connects back to the atrium. It also includes view ports to observe valve function, thin acrylic windows of ultrasound transmission, and transducer sites throughout the model to measure the wall pressure. It is also connected to analytical software to collect data from the test run. The ViViTest software control system produces simulated cardiovascular waveforms while simultaneously collecting pressures and valve flows. This device is also able to generate peripheral flows and evaluate left ventricular assist devices and other various assisting devices. Specifically, the Pulse Duplicator can be used

6 5 to test a variety of common cardiac conditions exemplified in the human body. For example, the flow of the fluid can be controlled to simulate a normal heart beat rate as well as cardiac arrhythmia and hypo and hypertensive states. Additional impressive features include both left and right heart configurations, and the ability to simulate pediatric cardiac conditions. Figure 1. ViVitro Pulse Duplicator [2] The Cardiovascular Mechanics Laboratory at the University of Ottawa has also used a left heart simulator to test their new leaflet sizing devices that make it easier for heart surgeons to take leaflet dimensions during surgery. They believe that valve-sparing surgery, or restoring the natural valve is a better option than valve replacement for patients because the living tissue remains in the heart. They aim to establish guidelines for aortic and mitral valve repair techniques based on their study of the mechanical properties of the repaired valves using the pulsatile heart simulator. Ultimately, our flow loop design could also provide surgeons in the United States with a device to establish the mechanical properties of replacement heart valves and develop innovative repair techniques Patent Search Results Patent # for a Pulsatile flow system for developing heart valves, was obtained by Steven Goldstein and Kirby S. Black in This invention includes a pulsatile flow loop wherein an aortic tissue valve can be mounted and studied in a dynamic flow environment similar to that of the human heart. The system includes a piston-type pump to drive the circulation which is connected to a waveform generator. A flexible elastomeric bladder simulating the ventricle connects to the aortic valve sample containing living cells through tubing. Tubes also connect the aortic valve to a compliance element, and back to the bladder. The fluid running through the system is similar to blood in that it is suitable for providing living cells with nutrients. An important issue at the time of development was a limited number of allograft heart valves available to those suffering from defective heart valves. An objective of the system was to provide an environment for porcine tissue valves to be converted from a xenograft to an autograph, while testing the effects of the flow rate, cycle frequency, and pressure on the valve performance. Although many of the elements in this system resemble

7 6 those of our flow loop, our design is more innovative and useful because it allows for testing of replacement heart valves of various types and lengths. The viewing ports in our design also allow for images and videos to be taken of the valves in action, which is extremely helpful when determining the source of error if the valve is failing. Patent # is for a Heart chamber simulator with electronic accelerated heart valve wear and fatigue test apparatus and method, patented in 1993 by Allen Eberhart. This replacement heart valve simulator tests the wear and fatigue of replacement heart valves so that the suitability of the valves for the human body can be evaluated. The device is powered by a fluid pulsed through the system by a pressure generator, utilizing a coil connected to flexible diaphragm. The coil is subjected to a magnetic field as well as a signal produced by the pressure generator. The magnetic interaction moves the diaphragm and replacement valve, which simulates the beating action of the heart. The pressure generator controls the type of signal, including pulsed, sinusoidal or triangular waveforms. It has the ability to simulate arrhythmia and other cardiac conditions so that the data records may be used to predict defects in the replacement heart valves. It may also include signals recorded from an actual human heart to reproduce in vivo fluid conditions and evaluate the replacement valve performance. Our flow loop design is also more innovative than this system because we our using a pulsatile pressure pump for the ventricle as opposed to a coil and flexible diaphragm subjected to a magnetic field. The pressure pump more accurately simulates the systolic and diastolic cycles of the heart because it can be set to a specific pressure. 1.4 Map for the Rest of the Report The remaining portion of this report will be divided into sections 2 through 12. Section 2 will describe the project design, including an introduction, alternative designs, and the optimal design along with its objective, major components, and prototype. Sections 3 through 9 will address the realistic constraints, safety issues, impact of engineering solutions, life-long learning, budget, team member contributions and the conclusion of this design project. The references, acknowledgements and appendix with updated specifications will be included in sections 10, 11, and 12, respectively. 2 Project Design 2.1 Introduction The human heart is very unique and difficult to study, so simulations are often created to model the heart and figure out exactly how it functions. Our senior design team in the UConn Tissue Mechanics Lab has developed a pulsatile left heart simulator. This device simulates and recreates the hemodynamic pressure and flow conditions that exist in the left side of the heart. The client had expressed the need for a newly designed left heart simulator that functions more efficiently and allows the user to collect data more effectively than the previous system. The old device was oriented vertically, which made it difficult to install and change the valves being tested. The system also leaked significantly during testing and it was difficult to prevent the leaks. The horizontal orientation of our device allows for easier assembly, insertion and removal of the replacement heart valves. Each component is compression fit using a series of rods so that the components can be easily slid apart and

8 7 removed if necessary. The design of the ventricle chamber allows images to be taken of the inlet and outlet sides of both the mitral and aortic valves during testing. We chose to develop our first alternative design, with a few modifications, because it was superior to the other two alternative designs due to the valve mounting method. This mounting device was the easiest design and allows for greater versatility because valves of various diameters and lengths can easily be mounted into the device for testing Alternative Design 1 This design attempts to incorporate previously constructed elements from the current flow loop system with select new elements to create an improved pulsatile flow loop that simulates the hemodynamic conditions of the left side of the heart. The start of the flow loop is the atrium. The atrium is a large reservoir chamber that supplies fluid to the loop and holds the excess fluid not currently in use by the system. The atrium in the Solidworks design of Fig. 2 was built previously by a graduate student in Dr. Sun s lab. The next component is the mitral valve housing chamber, composed of Plexiglas (the whole system will be made of Plexiglas so that flow can be monitored visually). The housing chamber will fit the mitral valve in place by compressing the valve against the side of the output of the atrium. The compression will prevent leaks around the valve allowing the correct pressurization in the chambers. The flow will then continue on to the ventricle. Figure 2. SolidWorks Model of the Optimal Design The ventricle design was also previously adopted from the model in Dr. Sun s lab. It is a two piece hollow system that houses a latex sack that separates the air chamber. The bottom of the chamber is routed to a pulastile air pump that serves to pump the latex sack pushing fluid through the system in a manner simulating that of a heart beat. The pump has two knobs that control the systolic and diastolic pressures of the ventricle. As shown in Fig. 3, the set up of the ventricle is a square, with the flow entering then leaving in a right angle. This square design allows visualization of the two valves while the system is running. Cameras can be mounted on two of the sides of the ventricle which will allow visualization of both valves simultaneously without affecting the overall flow waveforms. The two paths of view cross

9 8 along the center of the ventricle and continue through the valve chambers until they reach view windows at either the exit from the atrium or the entrance to the compliance chambers. Figure 3. Solidworks Model of Ventricular Chamber Upon leaving the ventricular chamber the flow heads through the aortic valve housing chamber. In this design the aortic valve housing will also be a compression fit. The walls of the chamber will compress onto the annulus of the valve that is being implanted in the system. As the annulus is compressed it will eliminate leakage in the system which will maintain the integrity of the pressure waveforms. A flow meter will be implemented at the aortic valve. This device will collect and measure the pressure in the system and flow rate of the water throughout the test. The data is then sent to the computer where it can be analyzed using the DataTrax software. After passing through the aortic valve the fluid enters the compliance chambers before passing through a throttle valve and returning to the atrium. The compliance chambers are a series of air pockets that ease the pressure curves of the aortic valve. Water is incompressible so the air pockets serve to absorb pressure and soften the curves. The design incorporates a two chamber box that has two output ports. The one on the bottom of the chamber leads to the atrium whereas the other leads to an empty, compressible chamber. This chamber allows for some variability in the compliance. This chamber can be pressurized with more air or filled with water to lessen the air in the system. The key factor to making this flow loop work is to have adjustable compliance so that the pressure and flow waveforms adequately simulate that of the human body Alternative Design 2 This design is comprised of the same main components as the original design: the atrium, mitral valve, left ventricle, aortic valve, ascending aorta, compliance chambers and throttle valve. All of the large components are composed of clear, acrylic Plexiglas. As with the other alternative designs, the layout of this design is horizontal as opposed to the vertical layout of the original design. This design was inspired by the need for a pulsatile flow loop with an easier method to house and mount mechanical and biological heart valves while replicating the physiological waveforms of the human heart.

10 9 The major differences between this design and the other alternative designs lie in the mitral and aortic valve housing and mounting setup. In this model, both the mitral and aortic valve housings will have an inner mountings and outer chambers. The outer housing compartments will be compression fit to the ventricular chamber via four long screws running through both the ventricle and valve chambers. The valve chambers will also be compression fit to the atrium and ascending aorta in the same manner. By loosening the screws, the outer compartment will be able to slide down to reveal the valves. For the mitral valve, the inner mounting will consist of two aluminum plates compressing the mitral valve annulus to the valve-ventricle interface. At this position in both the mitral and aortic mountings, neoprene rubber gaskets will be used to secure the openings and prevent water leakage. It is extremely important that water leakage does not occur during testing as inaccurate flow rates, pressure readings and physiological waveforms may result. As compared to the mitral valve housing, the aortic valve inner mounting will allow for a variety of valve lengths. This is so that a porcine biological aortic root can be implemented into the flow loop. Because the size of this valve is larger, it more closely resembles the actual aortic valve of the human heart, which is an important aspect of this study. The aortic valve inner chamber will include a sliding aluminum base. The width of the aluminum mounting will be an inch long, minimally wider than the average diameter of the aortic valve. The perimeter of the mounting will be a half an inch high in order to compress the valve and maintain the integrity of its shape. An outer casing just high enough to slide over the perimeter wall will be implemented so that it can slide out to four inches but maintain the supporting mounting structure. Screws located on both sides of the valve mounting at two inches and four inches allow the valve to be securely locked in place. This way, one would simply have to unscrew and slide out the outer aortic housing to adjust the length of inner valve mounting to accommodate a switch from a mechanical aortic valve to a bioprosthetic aortic root. Images of the mitral and aortic valves during the test will be obtainable through viewing ports located on both sides of the ventricular chamber. This will allow for images of the valves to be obtained from both the inlet and outlet sides, as requested by the client. The base of the ventricle will contain two viewing ports, one aligned with each valve. Images obtained from these ports will be of the water flowing from the mitral valve to the ventricle, and from the ventricle to the aortic valve. The other two viewing ports will be located on the top of the mitral and aortic chambers to observe the flow of water from the atrium through the mitral valve, and from the aortic valve out to the aortic chamber Alternative Design 3 Similar to the two previous designs, this design uses the same basic device structure (refer to Fig. 2) including the atrium, mitral valve, left ventricle, aortic valve, ascending aorta, compliance chambers, and throttle valve, connected by tubing. There are three major goals of this design: to find a more effective method of mounting valves into the device, to design a way to image the valves from both sides during testing, and to provide a heat reservoir around the atrium. The device will have a horizontal orientation while still producing the same waveforms as the human heart.

11 Mounting Device In order to allow for testing on several different sized valves or valves inside stints, a more versatile design is used for the mounting devices. The valve or stint is mounted between two 6061 aluminum plates which are attached to the ventricle chamber on one side. The two aluminum plates are attached by pins in each of the four corners to keep them in alignment with each other. There are also springs between the plates in each of the four corners to push the plates apart. The springs are only attached to one of the plates so that they can be pulled apart to allow for easier access to the mounting site. A diagram of the structure of this portion of the flow loop is shown below in Fig. 4. Since the tests on this device will involve valves and stints of different lengths it is necessary to control the distance between the aluminum plates. This is done using a C-clamp on either side of the mount between the two aluminum plates. This clamp is adjustable from zero to four inches so it allows for the mounting of several different valves and stints. Attached to the side opposite the ventricle is an L-shaped portion, described in the following section, followed by the rest of the flow loop. On the aortic side, a flow meter which sends information to the computer is attached before continuing with the remainder of the flow loop. Figure 4. Top View of Aortic Valve Mount Imaging As described in design one, cameras are mounted on two sides of the ventricle to simultaneously image the output side of the mitral valve and the input side of the aortic valve during testing. The client also wants the ability to image the valves from the opposite side during testing. To resolve this issue, the tubing directly before and after the ventricle is replaced with an L-shaped portion of Plexiglas. A camera is placed at the imaging access point, as indicated below in Fig. 5. There are two of these segments in the flow loop, one before the ventricle to image the input side of the mitral valve and another directly after the ventricle to image the output side of the aortic valve.

12 11 Figure 5. Secondary Imaging Access Heat Reservoir In order to provide an environment more comparable to that of the human heart, there is a heat reservoir surrounding the atrium chamber to heat the fluid going through the flow loop. This is a compartment a few inches longer and wider than the atrium, as shown in Fig. 6, and kept at body temperature, 37 C. The temperature is controlled using an open-topped box to hold water, a device to change the temperature of the water, and the atrium chamber. To control the temperature of the water, an aquarium heater is installed into the box. Figure 6. Top View of Heat Reservoir 2.2 Optimal Design Objective The goal of this project was to build a pulsatile flow loop that simulates the hemodynamic pressure and flow conditions of the left side of the heart. It follows the blood flow from the left atrium all the way through to the ascending aorta. Along the way it passes through the mitral valve, the left ventricle, and the aortic valve. Upon completing travel through the ascending aorta the fluids must pass through a section that simulates the

13 12 resistance of the body on blood flow before the blood returns to the heart. After passing through this section the fluid returns to the left atrium so it can pass through the loop again. Implementation of this device revolves around hemodynamic studies of either the mitral or aortic valve. Before a mechanical or bioprosthetic valve can be approved for use in clinical testing it must go through a rigorous set of tests to prove that it will function properly in the human body. There was an flow loop in Dr. Sun s lab that was capable of doing this but was not designed to accommodate his future studies. One key aspect of the new flow loop is the capability to mount a native biological aorta into the loop in the position of the aortic valve. The native aortic leaflets will function as they would in an actual heart. One of the reasons this is important is that it allows for testing of a different type of bioprosthetic valve, the percutaneous heart valve. These types of valves have been in development over the last decade and can be implanted into a human with the use of a minimally invasive procedure. The problem with testing these valves is that they are usually mounted in a stent and need to be expanded into the diseased tissue via a catheter balloon system. This means that there is no good way to mount this valve into the existing loop to study its flow dynamics. The addition of the native aorta into the loop creates a medium into which a percutaneous valve can be implanted. This not only allows for hemodynamic studies but also allows studies to be done on the radial strength of the valves in actual tissue. Tests can be performed to see what kind of back-pressures from the ascending aorta will cause slippage of the valve, which would most likely result in death if it happened in a patient. A schematic of the device is shown below in Fig. 7. Figure 7. Schematic of Optimal Design Subunits Atrium Chamber The first component of the pulsatile flow loop is the atrium chamber. Water is supply to the flow loop through the atrium. The main purpose of the atrium chamber is to serve as a reservoir, holding excess water not currently used by the system. Figure 8 shows the atrium previously built by a graduate student of Dr. Sun s research team. The atrium design consists of a 5.75 by by 3.25 open topped chamber of Plexiglas. The large open-topped chamber allows for a fluctuation in volume without causing a drastic increase in pressure throughout the rest of the system. This is important because an increase in pressure occurring at the beginning

14 13 of the loop would be experienced throughout the rest of the system. As a result, pressure readings obtained at the mitral and aortic valves would be inaccurate, as would the physiological waveforms of the system. A PVC tube connects the bottom of the atrium to a 5.25 by 3.5 by 3 block of Plexiglas. This component has a hole allowing the water to flow through to the mitral valve. The mitral valve chamber will be compression fit against the side of the output of the atrium which will prevent leaks around the valve. Four set screws run through the bottom atrium component, mitral valve chamber and ventricular chamber to pressurize the system. This will ensure pressurization and correct pressure waveforms to be produced by the mitral valve. A PVC tube is connected to the side of the bottom atrium chamber to allow the water traveling throughout the system to return to the atrium and flow through the system again. Figure 8. SolidWorks Image of Atrium Chamber Valve Housing The designs of the mitral and aortic valve housings are the same, allowing for mechanical, bioprosthetic and biological tissue valves to be securely implemented into the flow loop. The mitral valve is a key aspect of this flow loop because it acts as a doorway for fluid to flow through to the ventricle so it can then be pumped throughout the system. The mitral valve is a one way valve. As fluid is pulled into the ventricle, the two valve leaflets open allowing fluid passage. When the ventricle contracts pushing fluid out, the pressure of the two leaflets pushes them backwards, closing off the path. The mitral valve used in this system is a mechanical valve available in Dr. Sun s laboratory. Valves are manufactured and sold to hospitals, making it very difficult and expensive to obtain new ones. One of the key goals of this project is to be able to incorporate different sizes and types of valves into the mitral and aortic positions. The design of the valve housing reflects this issue. The housing consists of a solid aluminum rectangle (5.25 x3 x0.5 ) with a hole bored into it with a diameter of 1. This

15 14 hole extends through the majority of the rectangle (0.4 ) until the end where the diameter is smaller, allowing the valve to rest against a flat surface (Fig. 9). A biological tissue valve is inserted in the aortic valve position. This valve type consists of a sewing ring or annulus at the base that is supporting three struts. Between these supports are three tissue leaflets that meet in the middle. A crucial characteristic when attaching one of these valves is that the three struts must have a small amount of space to flex as the valve opens. To fix this valve in place, a thin-walled steel cylinder with an outer diameter the same as the diameter of the larger hole will slide down onto the valve once it has been placed in the chamber. The cylinder will be pushed down to compress the valve in place to prevent sliding. Along the rectangle four holes will be drilled from each edge face. Set-screws will be used to hold the cylinder in place, holding the valve steady in the process. Figure 9. Valve Housing Pulsatile Air Pump A pulsatile air pump is attached to the bottom of the ventricle chamber to pump fluid through the system simulating that of a heartbeat. The pump previously used in Dr. Sun s laboratory was implemented as it has accurately pumped fluid through the original flow loop in previous tests. It was able to generate proper pressure and fluid rates to produce physiological waveforms resembling those produced by a human heart. The pulsatile air pump is capable of producing adjustable systolic and diastolic pressures. The pump alternates between two phases (systole and diastole). The systolic phase is adjustable using the top dial control (Fig. 10) and acts to push air into the ventricle, simulating the contraction of the heart. The diastolic phase is controlled by the bottom dial and does the opposite. Air is pulled into the pump out of the ventricle to simulate the relaxing of the heart. The other controls included on the pump are systolic duration, which has been kept at 350 ms, and the heart rate in beats per minute. The power switch as also on this front panel on the bottom left.

16 15 Figure 10. Pulsatile Air Pump Front Panel Ventricular Chamber In the human body, the left ventricle is responsible for pumping blood through the aortic valve into the ascending aorta and out to the rest of the body. In this flow loop, the ventricle pumps fluid through the system powered by the pulsatile air pump described in Section The ventricle design is adopted from the pre-existing ventricle developed by Dr. Sun s research team, consisting of a latex sack housed in an airtight chamber. The pulsatile air pump is connected to the bottom of the chamber. As seen in Fig. 11, the ventricle chamber is designed as a square, with the flow entering then leaving in a right angle. The top portion of the ventricular chamber is a 5.25 x5.25 x3 block with a 3 diameter cavity in the center. This square design allows for visualization of the mitral and aortic valves while the system is running. Cameras can be mounted on two of the sides of the ventricle which will allow visualization of both valves simultaneously without affecting the overall physiological flow waveforms. The two paths of view cross along the center of the ventricle and continue through the valve chambers until they reach view windows at either the exit from the atrium, or the entrance to the compliance chambers. Both windows are detachable but the window following the aortic valve must be removed to attach the first compliance chamber and obtain more accurate waveforms. Each heartbeat simulated by the pulsatile air pump pushes an amount of fluid through the system determined by the systolic and diastolic pressures applied by the pump to the left ventricle. The human heart contracts during the systolic phase of the heartbeat. To implement the systolic phase into the flow loop, the pump pushes air through a tube into the airtight chamber housing the latex sack, directly influencing the internal pressure. As a result, the sack collapses inward, pushing fluid through the aortic valve. Simultaneously, this contraction of the ventricle applies pressure to the mitral valve which will close it, preventing water from entering the atrium via this route. In contrast, the diastolic phase of the heartbeat is when the ventricle

17 16 relaxes and fluid flows through the mitral valve to refill the ventricle. To simulate the diastolic phase, the pump draws air from the ventricular chamber, creating a vacuum. As a result, the sack inflates to its original size and is filled with fluid from the atrium through the one way mitral valve. This process accurately simulates the muscle contraction and relaxation periods of the human heart, enabling the valve function to be focused on during testing. Figure 11. SolidWorks Model of Ventricular Chamber Ascending Aorta The ascending aorta is the component of the heart that delivers the oxygenated blood coming from the heart out to the entire body. The ascending aorta is the largest artery in the body and it splits into smaller portions as it moves further away from the heart. In the flow loop, this component is made up of a series of tubing to simulate the separation of the blood into different sections to travel throughout the body. Tubing along is a very tough and resilient material so that it can withstand high pressures. Since the arteries in the body actually have an elastic component, the flow loop must compensate for the rigidity of this tubing. This is achieved by incorporating two separate compliance chambers in the ascending aorta. Compliance measures the ability of the walls of arteries and veins to contract and expand as the interior pressure changes. The compliance chambers mainly soften the pressure waveforms obtain from the loop but they can also shift the waves up or down Aortic Turn The aortic turn is the first component simulating the branching of the blood from the aortic valve out to the rest of the body. It is a 5.25 by 3.25 by 3 block of Plexiglas with two holes of 1 diameter; one running straight through it to compliance chamber I and one off at a right angle to compliance chamber II Compliance Chamber I The outer tube of this chamber is approximately five inches in length and has an inner diameter of three inches and an outer diameter of three and a half inches. The chamber was cut in half and a sheet of Dragon Skin 10 Platinum Cure Silicone Rubber was placed in between the two pieces (Fig. 12). To make attaching the chamber onto the rest of the device easier, the two halves were glued to the silicone sheet, creating one piece. Gasket material was also glued

18 17 to either end of the chamber to prevent leaking when assembled. An end plate compresses the chamber to the block after the aortic valve using threaded rods, washers, and wing nuts. The first compartment, closest to the aortic valve, fills with water and air is let out of the system through the pressure tap on the top. The second compartment is air-tight so that a syringe or hand pump, attached to the pressure tap, can pressurize the compartment and control the amount of compliance. Drawing air out of the second compartment allows the membrane to expand more and pushing air in limits the extent of expansion. These properties can soften or spike the waveforms depending on the extent of each action. Figure 12. Image of Compliance Chamber I Compliance Chamber II The outer tube of this chamber is approximately eight inches in length and has an inner diameter of three inches and an outer diameter of three and a half inches. The tube within the chamber is made up of three layered commercial punch balloons with the ends cut off. As seen in Fig. 13, the balloons are connected to hose barbs using hose clamps and the hose barbs connect to the rest of the system. The chamber is air-tight and connected to a controllable pressure pump gauge through the pressure tap so that as the pressure within the tube is changed, the size of the inner balloon changes accordingly. The device has this feature because the pressure at which the best waveforms are produced is unknown. The ability to adjust the amount of compliance applied to the system provides a method for adjustment in troubleshooting if the waveforms obtained at first are not quite what is expected. Increasing the pressure in the chamber increases the aortic pressure, shifting the range of the waveforms. The fluid flows through the rubber compartment within the tube so that the pressure can adequately impact the flow.

19 18 Figure 13. Image of Compliance Chamber II Data Acquisition Data is acquired from the system using either the square-wave electromagnetic flow meter or pressure transducers. Both are run using the LabScribe2 program on the lab computer. Data comes in from both sources as a voltage and is scaled to read as either liters per minute or millimeters mercury. The flowmeter probe is mounted in the system right before the aortic valve housing and is connected to the square-wave electromagnetic flow meter. This detects the flow rate of the water flowing throughout the system and will be able to detect regurgitation if it is present. Pressure transducers are attached to pressure taps located at the top of the ventricle and aortic turn components which measure the left ventricular and aortic pressures, respectively. The data obtained from these transducers allow the pressure waveforms of the running system to be produced and analyzed. A pulsatile flowmeter is implemented in the flow loop right before the water returns to the bottom atrium component. The flowmeter includes a metal piece that moves up and down the scale as the flow changes. The reading should be taken, not from the top of the metal piece, but from the widest part of it. An average of the highest reading and lowest reading gives an approximation for the average flow rate throughout the system. The purpose of including this flowmeter while still using the electromagnetic flowmeter was to have two methods of reading the flow rate and also to have a more immediate method of obtaining this reading. The flowmeter must be installed so that it is upright and no stress is put on the body of the meter Throttle Valve The throttle valve acts to regulate the overall flow throughout the system. It has a numbered dial from 0 to 5 (Fig. 14) that indicates how large the opening is and can be easily adjusted. This acts to retain a higher pressure system in the aortic section and a lower pressure system in the atrium. Increasing the number on the dial increases the overall flow of the system

20 19 and decreases the aortic pressure whereas reducing the number on the dial decreases the flow and increases the aortic pressure. The throttle valve was taken from the ViVitro flow loop and implemented into this system after other valves were tested and found to be unsatisfactory. Figure 14. Throttle Valve 2.3 Prototype The first prototype was a combination of all the sections listed in the original Optimal Design except for Compliance Chamber II immediately after the aortic valve. This was added after we did our first assembly and decided that the pressure waveforms were not satisfactory. The original prototype also had the balloon compliance chamber facing in the opposite direction that it is now. The 180 degree rotation from its original place allowed us to connect the outlet flow to the inlet flow with greater ease. Our original design for compliance chamber II included a silicone tube instead of the three layered balloons. We originally thought this would successfully expand to soften the pressure waveforms. However, after a few days of testing, the silicone developed a small hole. It didn t take long for the tube to burst due to the pressure and fluid flow of the system. We thought of replacing it with another silicone tube but we realized that this problem may reoccur throughout the life of our flow loop. To ensure the user would not have to complete the difficult task of replacing the silicone tube, we decided to implement the three layered balloon system. This way, the material is more resilient and will not pop under pressure. This resulted in a reliable compliance system that will not have to be replaced as long as the system is in use. We also originally had hard plastic piping connecting the outlet to the inlet flow but this was eventually eliminated and replaced with soft rubber tubing so that we could switch out the throttle valve we had in the system and replace it with the old throttle valve used in the ViVitro system. This softer tubing also makes it much easier to drain the system of water after each test is complete. Other than a few minor changes our original prototype worked very well. We had to sort out a few issues with leaking sections from the tube threadings but these were easily fixed with silicone. A SolidWorks image of the final device design is shown below in Fig. 15.

21 20 Figure 15. SolidWorks Model of Final Design 3 Realistic Constraints 3.1 Engineering Standards As requested by the client, the final pulsatile flow loop model must allow implementation of mechanical and bioprosthetic valves of various sizes while producing accurate physiological waveforms resembling those produced by the human heart. Each component of the flow loop must be compression fit as to not leak or alter the pressure or fluid flow rate of the entire system. If the waveforms are inaccurate or if a problem exists with the valve function, such as regurgitation, the system must be re-evaluated to find a solution to the problem. This may include modifications to the valve mountings or ventricle set-up. The whole system must be constantly monitored to locate and prevent problems. 3.2 Economic Constraints Although the client was quite generous with the budget, we had to keep it in mind at all times. We did not go over the budget and ordered our materials early on to be prepared if we needed to troubleshoot our design and order additional components. 3.3 Environmental Constraints To the extent of our design, the flow loop will only contain water running through it. Although the water will be supplied by Dr. Sun s laboratory, we can reuse the water flowing through the system multiple times as to not take advantage of the supply. We had to be conscious of leaks and clean them to avoid biological hazards associated with the use of the biological tissue valve.

22 Sustainability Due to the fact that in the trial and error period of testing the system consists of running the system countless times a day, it is important that our design is stable and resilient. The Plexiglas of the previous flow loop design cracked at the location of the screw insertions over time. To avoid this problem, our design implemented smaller screws, enabling the Plexiglas to withstand the pressure of the system. More importantly, it is crucial that the replacement valves remain in good condition and continue to function properly. Because the valves currently used in experimentation are about five years old, we must constantly monitor their function. If one of the valves is no longer suitable for testing, it may be necessary to order a new valve which would be very expensive. It is important that the biological tissue valve be removed from the system when not in use and returned to the glutaraldehyde solution so it doesn t dry out and still functions properly. It is also important that the pulsatile air pump functions properly throughout the trial runs. This is because if the correct systolic or diastolic pressure isn t implemented into the system from the beginning, it is not possible for the accurate physiological waveforms to be produced. It would also be very expensive to replace such a crucial component of this system. The flowmeter probe is also extremely sensitive and should be handled with care. Too much pressure applied can skew the detected flow rate, which will also result in inaccurate results. It is important that this flowmeter remains accurate and reliable throughout the duration that the flow loop is used as it would be very expensive to replace. 3.5 Manufacturability Although much of the material will be provided by the Tissue Mechanics Lab, it was necessary to construct many components from Plexiglas and aluminum. The valve mountings, ventricle chamber, bottom atrium component, aortic turn and compliance tubes were machined in the UConn Machine Shop. Because the proposed design did not hinder accurate physiological waveforms in any way, it wasn t necessary to redesign specific components. All components can be easily reproduced using a CNC machine, milling machine and lathe. 3.6 Health and Safety Constraints When working with biological tissue it is important to follow the UCONN Environmental Health and Safety standards. Additionally, one should use caution when working with fluids that have passed through any biological tissues. Gloves should be worn whenever working with the device. One must also use caution when working with the electrical devices such as the electromagnetic flow meter. Electric shock may occur if one is careless when dealing with fluids near electrical outlets or open wires. 3.7 Social Constraints Once the initial design was constructed, troubleshooting and modifications were necessary to achieve the appropriate cardiovascular waveform results. Time was a great constraint the second semester due to the need to troubleshoot the square-wave electromagnetic flow meter, experiment with the pressure settings of the compliance chambers, pulsatile pump and throttle valve, and silicone the various leaks that continued to

23 22 occur. Each group member was able to sacrifice and manage their time so that the completed project was successful and satisfactory to the client. 4 Safety Issues The main safety issue associated with this device is the use of biological tissue. All users should handle biological tissue according to the UCONN Environmental Health and Safety standards. While most of the tissue used in the device should be harmless (the porcine tissue is the the same meat as would go to the local grocery store) if human tissue is used extreme precautions should be used. Caution should also be used when using any of the electrical devices. Irresponsible behavior could lead to electric shock. When working with the flow loop near devices such as the electromagnetic flow meter one should be careful not to spill near any wires or electrical outlets. 5 Impact of Engineering Solutions The device itself will not have a direct impact on society because it is a model of a heart, as opposed to a device that will, for example, be designed, tested, and implanted into an individual. At the same time, the implications of this device are potentially great. Now that it is complete, several different mechanical and bioprosthetic heart valves can be mounted and tested using the device. The device can be used to observe how the aortic and mitral heart valves function during the cardiac cycle through imaging the heart valves from the inlet and outlet sides. This will help gather additional information about heart valves to help improve the design of replacement heart valves and create additional solutions to the problem of heart disease. Because heart valve replacement surgery is quite common, testing of bioprosthetic heart valves for success in the in vitro environment will provide surgeons with the confidence that the valves will function properly in a patient. Patients will be able to understand that their new valve will function like their original valve, alleviating the fear that it might fail or that they might have to undergo another surgery to have it fixed. Currently, ViVitro Labs Inc. in Canada has developed the world-wide known ViVitro Pulse Duplicator in which they rent out to companies and surgeons to test their replacement heart valves. Additionally, companies and surgeons have the option of sending their heart valves to ViVitro to have technicians complete the testing. Our pulsatile left heart simulator can be easily manufactured and marketed so that companies or surgeons in need of testing replacement heart valves could potentially purchase a flow loop for themselves. This way, it would be less of a hassle and companies could test the replacement valves regularly. An increase in heart valve replacement research would result, aiming for the ability to improve the lives of those suffering from heart valve disease. 6 Life-Long Learning Through researching and designing modifications for the pulsatile flow loop, we acquired knowledge and experience that will be of great use in future projects and ultimately in industry. Because an understanding of how the components of the flow loop combine to