Stephen R. Topaz
After graduating from Purdue University with a degree in Mechanical Engineering, Mr.Topaz joined Dr. Willem Kolff’s lab at the Cleveland Clinic. Here, he helped design, build, and operate artificial hearts, developed the Intra-Aortic Balloon Pump, and instrumented hyperbaric chambers among other endeavors. Following this, he worked with several renowned academic institutions and medical device companies. These included Johns Hopkins University, Rutgers University, University of Utah, Hoffman LaRoche, Haemontics, Nova Biomedical, Abbott Labs, and Symbion. At these institutions, he was involved in the design and development of several medical technologies. He eventually retired to Oregon, working with the University of Kentucky on mobile devices including an internal cardiac turbine blood pump and developed a non-cavitating propeller for ship propulsion or pumping blood.
1 | INTRODUCTION
The title for this editorial comes from a remark made to a daughter by her mother. A young lady complained to her mother about living in the desert with her husband. This was during World War II and her husband was part of the atomic bomb project. The lady wrote, “There is nothing here, it is a desert.” Her mother wrote back, “Look Again.” Those two words ended up being the inspiration for a wonderful book on the wildflowers of the desert.
Over the years, we developed measuring equipment and techniques that could be used in other disciplines. We filled a warehouse of knowledge that others could use. We discovered that a great deal of our prior medical knowledge was wrong and we corrected it. We also observed many effects, artifacts, and other discoveries that were not useful for the problems prevalent at the time they were made.
So, we must ask ourselves about what we may have overlooked. To begin with, a quick glance at our exhibitions shows no collections of developing artificial kidneys, heart-lung machines, artificial valves, etc. This is because our past developments are now standard medical devices. However, this has negatively impacted our development work. New researchers stopped entering our society and developing; instead, they started using what we had developed. Nevertheless, we still have a lot of development to finish despite losing a few thousand potential developers. It is now time to investigate more fully what we left behind. It is now time to “Look Again.”
I am a mechanical engineer by profession. My foray into medicine began when I repaired braces at a YMCA camp for disabled children at Lake Clendening, Ohio.
One summer in the 1960s, I was looking for a place to work and there were three men that showed some interest in me. They were part of the founding fathers of the American Society for Artificial Internal Organs (ASAIO): C. Walton Lillihei, Adrian Kantrowitz, and Willem Kolff. I started to work for Dr. Kolff and over the years, both Dr. Lillihei and Dr. Kantrowitz played a surprising part in my work. There is one thing that these men all had in common, one thing that made them stand out beyond their ability; courage!
The monumental part that Dr. Kantorwitz played in the successful clinical acceptance of the balloon pump was because he could keep doing clinical research on the balloon pump as he had a grant that funded cardiac assist device development. He also had a crew of researchers that included some with engineering backgrounds. This was especially significant in light of the NIH requirement that clinical testing of medical devices not be done by the developing team. Added to this was his long history of trying to develop heart assist devices and being a great surgeon. An unintended benefit of his work was that he could not be accused of promoting his own invention since he did not invent the balloon pump.
At the Cleveland clinic, the Kolff department was in charge of the clinical operations of the heart-lung machine and artificial kidney (Figure 1). A NASA engineer, Kirby Hiller, helped design a pneumatic artificial heart driver tower as a research tool for Dr. Kolff’s lab. At that time, open-heart cases were done once a week, requiring 14 units of cross-matched blood for priming. The tubing
FIGURE 1 The Kolff lab on the sixth floor of the research building at the Cleveland Clinic. Dr. Moulopoulos can be seen working at the NASA artificial heart driver tower. On the far wall in the background, two mock circulations for testing artificial hearts and the balloon pump can be seen. The control panel with multiple dials designs the driving pressure wave form. The animal on the operating table has an artificial heart implanted. In this room, in 1961, several artificial organ replacement devices were being worked on.
sets and oxygenator setup were constructed in-house for each case as premade perfusion sets were not available. As the clinical use of extracorporeal perfusion started gaining ground, many previously held assumptions were turning out to be inaccurate, and these severely limited the success of the total artificial heart. For example, it had been assumed that the rate of flow needed in an extracorporeal circuit was 30 cc/kg/min. Another assumption was that anesthesia did not affect blood flow because the blood pressure stayed constant. The classic assumptions on range of cardiac output were also surprisingly limited. As the work on the artificial heart progressed and corrected some of these assumptions, this information became very useful for other specialties too.
Eventually, Dr. Kantorwitz presented to ASAIO, a reasonable group of successfully assisted patients that truly moved the use of the balloon pump forward.
2 | THE NEED F OR TEMPORARY CARDIAC ASSIS T
This was the medical climate for new devices in the early 60s. In that period, initial experience with clinical extracorporeal perfusion showed that normal hearts did not always resume pumping at a normal level. It was found that with some patients, just putting them back on the pump for a short time led to their hearts recovering enough to support the circulation.
The hunt was now on to find a pumping replacement that was not as large and limited as the extracorporeal heart-lung machines. A complicating factor was how the patients were to be cannulated. During this period, the blood for the extracorporeal support was removed through peripheral arteries and veins. These peripheral connection points were the usual location to connect the assist pumps to the patients. This meant that one team would start cannulating the patient before the main team could start working in the chest. Moreover, the cannulas were flow resistive when compared to the present-day ones and the patients tended to have a fair amount of calcium in the wrong places. In short, distant location, resistive flow, hemolyzing cannulas, and ineffective cardiac assist were how we started.
This is the theater that I was thrown into: From the engineering world of precision and calibration to a world of “It looks like this and that is the way it works.” I was an engineer and knew nothing about the medical world. While this may seem like an apparent disadvantage, it turned out to be quite the opposite. The medical staff would go to great ends to explain to me how things really worked, many times in better detail than they would explain to fellow medical staff.
3 | INITIAL WORK
When I joined Dr. Kolff’s lab, my first project was to transform a solenoid pump. The existing one was plagued with issues of overheating, blood cell destruction, and other structural issues. The key areas of interest for us were blood damage and blood flow which the pump made worse. The cumbersome tubing did not help either. The solution we came up with was not to handle or pump blood; rather, to use a balloon which could be rapidly inflated and deflated.
Spyridon D. Moulopoulos came up with an interesting idea in this regard after a morning conference, and we immediately
started working on developing a balloon pump prototype. We were able to test this balloon pump in a mock circulation before lunch the same day. The next step was to make a metal mold to dip coat a balloon, and by 4 pm that afternoon, we had the mold ready to be dipped (Figure 2). That was a Monday, and that Wednesday, a day that the usual artificial heart experiments were done, the balloon pump was ready for an animal test. The artificial heart experiments required several donor dogs for priming the heart-lung machine and one of these animals was used to verify that the balloon pump worked in animals. One balloon assist was done on a patient that was undergoing cardiac catheterization where the patient was supported but the heart never resumed normal function. The information collected during this procedure on the cineangiography table was eye-opening. The balloon pump did move a large amount of blood, blood pressure was maintained, the body was kept viable, but the heart never recovered. At the postmortem, it was found that the cardiac muscle was heavily loaded with calcium deposits. The balloon could pump blood, but it did not treat medical problems.
4 | THE SCIENCE BEHIND THE SCENES
4.1 | Aortic geometry and mechanics
The aorta at first glance is a tapered tube with a larger opening at one end and a smaller opening at the other end (Figure 3). But, having a curve, being distensible, and having controllable features, makes it anything but a tapered tube. Another small feature that complicates the function of the aorta is that it has tubes (arteries) exiting from it. The first question when examining the aorta is, what is the real exit area? Medically, it is understood that the flow through these arteries is variable. How much of the pumped blood will be lost to the side branches is an obvious question with no measurable answer. Other questions arise when it is realized that the volume of the aortic wall is fixed, which means that if you increase the diameter of the aorta by increasing the local blood pressure, the aortic length becomes shorter. This geometric fact affects blood
flow and pulse pressures.
FIGURE 2 Long balloon molds. Some of these shapes were to investigate if it was possible to change the amount of blood leaving the different ends of the balloon. The addition of different size balloons on the same catheter was tried to build a device that could be placed in the arch.
FIGURE 3 A tapered tube and the aorta. The shapes of these tubes and diagram of aorta appear the same but hydrolytically are very different when studied under pulsatile flow. The flow pulse timing greatly affects the body’s response. A tapered tube has a larger opening at one end and a smaller opening at the other end, therefore the flow velocity changes from one end to the other by the relationships of the area at these points. The fluid velocity entering the large end increases as it exits the small end and vice versa. A tapered tube is considered rigid.
In the 60s at New York University, a supercomputer was used to create an animation of the left atrium. The biggest problem for the programmer was how to describe the atrium’s boundaries. The atrium is bound to the body by the pulmonary veins and as it fills, it gets bigger, the mitral valve moves away from the pulmonary veins, and the volume in the atria gets larger. When the atrium expels blood into the ventricle, the mitral valve moves closer to the pulmonary veins. Blood passes through the mitral valve because the valve is moving, and only after a finite time does the blood volume actually move.
The ventricle and the aorta play a similar game where the mechanical movement of the blood-containing tissue moves around the blood and then the blood itself moves. The choice of the point of reference for movement measurement becomes very important when trying to describe this action. What does all this mechanical movement have to do with balloon pumping or more importantly the improvement of balloon pumping? Should the balloon be placed in the ascending aorta? Could electrically stimulating the active locations in the ascending aorta help perfusion? Some work has been done using a segmented balloon to be able to place part of the balloon very close to the valve and it has been seen to improve flow.
FIGURE 4 The classic location of the IAPB mainly because the catheter used would not bend through the aortic arch. The inflated balloon would also straighten with the possible insertion into an existing artery if placed elsewhere.
4.2 | Balloon pump placement
The aortic balloon is placed high in the aorta (Figure 4). There, it expands to expel blood and collapses to reduce the outflow resistance of the left ventricle, all synchronized with the normal heartbeat. The blood flow away from the balloon is from the ends of the balloon; therefore some blood flows in the normal direction, and some in the opposite direction. This means that the blood flow direction changes proximal from the balloon pump.
As the number of patients being connected to the extracorporeal pumps increased, it became obvious that peripheral cannulation was not optimal; hence, cannulation of the ascending aorta became the preferred way to return blood to the circulatory system. An added benefit was the decreased operating time (Figure 5).
The science of assisting the heart also improved. It was now possible to implant devices that could assist the heart and the most convenient location to return the blood was the descending aorta—about where the balloon pump would be placed. Clinical observations showed that the more effective way to assist the heart was to return the blood to the ascending aorta. These observations indicated that the aorta is sensitive to the location of blood return when it comes to long-term support.
4.3 | Blood flow
There were quite a few unexplained observations regarding blood flow. For instance, it was understood that the higher the blood pressure, the greater the blood flow, provided the resistance stayed constant. However, we also knew that extreme exercise required more blood flow and blood pressure usually increased in a normal patient and not in a trained athlete. But we did not fully understand how much the flow resistance changed, and likewise how low the blood flow was reduced with a minimal change in blood pressure when we anesthetized a patient.
FIGURE 5 The engineer’s view of the peripheral injection point for cardiac assist. This point was used as a blood return port for the first extracorporeal heart-lung machine. The pump shown would first withdraw blood to lower the aortic pressure to increase the ejection flow volume of the failing ventricle, and then return the blood to increase the aortic pressure and perfuse the body. The flow characteristics of the cannula damaged the blood and limited the flow volume that could be obtained.
The other aspect of blood flow is its control. How is blood flow controlled and for what reason do we need to change the rate of blood flow? The answer lies in what the additional flow is needed for. This can include functions such as removal of heat, aerobic muscular activity, delivery of chemical compounds, removal of carbon dioxide, mechanical energy, pulse or pressure, the transport of fluids, etc. The homeostatic system holds the control switch and there is not a single indicator that is available to the outside to indicate what the cause for the output change is in such conditions.
One experiment that I observed was the controlled generation of hemorrhagic shock by removing a fixed amount of blood, checking the blood pressure, waiting a short time, and repeating this process until the blood pressure began to fall, indicating the initial stages of hemorrhagic shock. In this procedure, we observed that the tissue pH started to drop 20 min before the standard indicators of shock were present (Figure 6). The normal tissue pH is in the range of 5 to 6, not the 7.35 to 7.45 range of blood pH. The question to be answered is when does shock start? When does the body start responding to the blood loss? When does loss of homeostatic control start? Extending that question in patients with failing hemodynamics, when do the vascular control systems start compensating for the hemodynamic insult, thereby masking initial symptoms?
The Intra-Aortic Balloon Pump has sometimes been shown to increase cardiac output, especially when the heart cannot meet the demands of the body. If you pump with an intra-aortic balloon in the body of a healthy and unanesthetized animal, blood flow increases and then
FIGURE 6 Shock test in a normal dog. These measurements suggest that vascular compensation mechanisms that operate to stabilize the body are not the classical measurements used to describe when corrective actions should be started. The use of a muscle metabolic mechanism is not a standard clinical data point.
FIGURE 7 The compensation mechanisms for regulation of blood flow change with the level of anesthesia. The true measure of a device’s effect must be indexed with the level of anesthesia and the operational level of the vascular system.
drops to the pre-pump level in about 10 s. When the same is done in a deeply anesthetized animal, the cardiac output increases greatly. While the anesthetized animal has a normal blood pressure, the cardiac output is reduced. The more important observation in these experiments is the speed at which the cardiac system reacts to changes in blood flow (Figure 7).
5 | FUTURE DIRECTIONS
What do these little observations mean? Clearly, a better understanding of how anesthesia affects the vascular system and other systems would be very helpful for long-term patient care. While deep anesthesia can help demonstrate how pumping devices change blood flow, knowing its effect and calibrating it could make it useful as a tool to indicate the overall condition of the un-anesthetized patient.
The neuro-mechanical responses of the aorta should be understood so that better balloons can be designed, and better placements can be instituted for improved blood pumping. These responses could and should be studied with the thought that perhaps some electrical stimulation timed with the mechanical pumping might further improve the efficiency of the balloon pump. Monitoring these responses just might be a more accurate way of timing the pumping in order to increase device efficiency.
The question of how to better wean the balloon pumping and return the vascular system to its unassisted state is one of those continuing problems that we have yet to solve. At the other end of the spectrum is the question of when should we begin to assist. Severe hemodynamic compromise, while a definite indicator to assist, is not the most ideal time to start helping a patient.
6 | FINAL THOUGHTS
We encountered many failures on this path. The biggest one was not continuing to work with Dr. Kolff at the Cleveland Clinic. Both Dr. Kolff and I left for the same reason. The governing body decided that if you were not an MD or PhD you could not be on staff. The Kolff lab could not operate without that strange mix of specialties that generally did not have those titles. I, being just a BSME, would lose my faculty position; so, I went to Johns Hopkins to work with Vincent Gott in the department of cardiovascular surgery. In addition, working with regulatory bodies was at times frustrating as they were not very fast on the uptake of new technologies.
In retrospect, I would say that having specialized professionals (Doctors and Engineers) working on a shared objective is much better than a professional such as an academic bioengineer, with “half” the expertise in two intersecting fields such as medicine and engineering. In my case, being just an engineer working in a medical environment with strange titles such as Associate, Research Associate, Consultant, Development Engineer, etc., worked out quite well. The different entities just focused on bringing me in and I engineered.
In the end, I’d like to draw the reader’s attention to why we do all this. Once upon a time, I was in the business of developing a fetal monitor and during one of the clinical tests, a child was saved—a Hollywood type event!
After the child was delivered safely, I was with the medical team back in the coffee room, and I remarked that no one had said “Thank You” to us. Dr. Joe Poppers responded, “Steve, our job is to save lives, not get thanks”. Over the years, I have seen that many little things have been done, sometimes far removed from the patient, that have saved lives and no one said, “Thank You.” In fact, much of what we do will never get a “Thank You,” but our business is still saving lives. Let us just keep on doing that.
Appreciation for editorial support to Danial Ahmad, MD, MPH, Editorial Coordinator of Artificial Organs.
Stephen R. Topaz
SP Tech, St. Helens, Oregon, USA
Stephen R. Topaz, SP Tech, 360 St. Helens Street,
St. Helens, OR 97051, USA.