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WGR: This is Thursday, October 18, 1979 in Minneapolis at the Marquette Hotel and we have the privilege of hearing from Dr. C. Walton Lillehei in our ongoing series of interviews with Pioneers in Cardiac Surgery. The whole purpose of this, of course, is to capture the voice, the experiences and the emotions of the particular investigator at the time when he first became involved with cardiac surgery and it is, indeed, a great pleasure to be able to talk to Walt Lillehei. Dr. Lillehei, if you would go ahead and take over now and just narrate in your own spontaneous way some of your feelings when you were first involved with cardiac surgery in its very beginning.
LILLEHEI: I think my interest really began in cardiac surgery when I was in the Department of Physiology during which time I spent 1-1/2 years in Dr. Visscher’s department and at that time he assigned, he suggested, a problem that I might work on that he was also interested in and that was producing heart failure in dogs. I had previously spent close to two years in Dr. Wangensteen’s laboratory in full time research and the entire time was devoted to gastrointestinal problems and, actually, that is where I eventually wrote a PhD thesis on is that work but, subsequently, did work for an advanced degree in physiology. The problem that Dr. Visscher had suggested was that he would like some dogs in chronic congestive heart failure to study electrolytes and other plasma flow, blood flow through the kidneys under conditions of failure and times when they were not in failure.
Dr. C. Walton Lillehei
Worked with Dr Clarence Crafoord at Karolinska Institute, Stockholm.
Developed pump oxygenator and used it for removal of atrial myxoma 1953 (patient still alive today).
Implanted one of first encapsulated pacemakers (1958).
Devised atrial correction approach for transposition of great vessels (1958).
Honorary member of Society of Thoracic Surgeons.
Chairman, Department of Surgery, University of Zurich, 1961 until retirement.
By 1949 or ’50, Dr. Dennis’ machine in the dog laboratory, which happened to be right next door to my laboratory where I was doing this work in physiology up in the attic of the physiology building, as they were bursting out of their seams at the time, he was able to perfuse dogs for 30 minutes with the heart-lung machine and open the heart and sew it up again and a good percentage of them, something like 70 percent, as I remember, would survive. Thirty minutes was considered a very long time for an open heart at that point in time and, of course, as I said we were very interested observers since we were working on heart problems. But, also being right next door, we were keenly interested in the work he was doing. And I think by 1951 (as I recall, April) Dr. Dennis felt that his machine reached the point where it was suitable to apply to an open heart operation in man, and he sought a case and was probably very illustrative of the state of the art at that time. This was the sixth patient chosen for this first open-heart operation by extracorporeal circulation in man attempted. And, as I say, it occurred in April, 1951.
The preoperative diagnosis was an atrial secundum defect on a six year old girl who was in very severe congestive heart failure and it is interesting, I think, to note that she had had two heart catheterizations and one exploratory thoracotomy with a finger exploration of the heart because it was felt that clinically it was evident that she had some mitral disease in addition to her left to right shunt. The surgeon who explored her found wide open mitral regurgitation and so the diagnosis then remained “ASD with mitral regurgitation”. Well, when the patient was put on the heart-lung machine without a vent at that time but when the heart was opened, there was a tremendous surprise because for several reasons. One is there was a tremendous flow of blood out of the open heart which was dozens of times larger than it had ever been seen in the dog and everybody was literally flabbergasted at that. But that only complicated the other problem because she did not have a secundum defect. She had a complete A-V canal and with all of this blood and totally unfamiliar anatomy, the surgeons, which was Dr. Dennis with Dr. Varco assisting him, did the very best they could and I happened to be in there looking over their shoulder as an observer and was literally amazed at the lack of any familiar sites in this bloody field.
I think that part, of course of the bloody field, was that Dr. Dennis felt at that time, as did Dr. Gibbon, that if you are going to put a patient on heart-lung bypass you must pump at least 100 cc per kilogram of body weight if you could. But that was only the beginning. To that you must add a factor for the left-to-right shunt, so they were attempting to pump somewhere in the vicinity of 150 cc per kilogram per body weight per minute, and since this young girl had a huge blood volume and had been in very severe failure and had lots of collateral circulation, of course, that added to the return to the open heart and, as I said, the procedure took something like 30 or 40 minutes. They sewed up what they thought was a hole. Of course, the patient did not come off the heart-lung machine and, at autopsy, which was very instructive to me and all the others who were present at this situation, found that the mitral valve had been sewed up. It might sound horrendous at this time in 1979, but in 1951 it was quite understandable. In fact, it was somewhat amazing that they sewed up anything because it was such a mess. Well, that was, of course, somewhat discouraging, but the pump (heart-lung machine) had worked well as near as anyone could tell. And Dr. Dennis did two more in ’51 – later in ’51 – before he moved to Brooklyn in 1952. And again, I think I might just mention it because it is very illustrative of what the problems were at that time. I mean there were multiple problems not only knowing if having a heart-lung machine would work but having the correct diagnosis and recognizing anatomy even if the diagnosis was correct.
The second case was a ventricular septal defect which was correctly diagnosed. The patient had pulmonary hypertension. It was a child who also had a patent ductus which, of course, was totally unrecognized and again when the heart was opened there was a tremendous influx of blood and a right ventriculotomy was made and that patient did not survive either.
The third patient was correctly diagnosed as an atrial septal defect of the secundum type and things went smoothly and everybody was extremely happy. As I say, I was present at these operations as an observer but not as part of the team. And suddenly, as her heart was being closed, the surgeon looked down to see air throughout the coronary arteries and palpating the aorta, which was crepitant, and with the very high flows, at that time which was still running these 100-150 cc per kilogram per minute if they could be obtained at least as much as they could, the pump had run dry and unfortunately that patient lived two or three days but remained in a coma and did not survive. Well, then, Dr. Dennis moved to Brooklyn to be Chief of Surgery at Downstate Division of the New York State University. Of course, he took his heart-lung machine with him.
But the next important event, I think, as far as open heart surgery, and I think it is of some interest, that many developments that did lead to open heart surgery started in Dr. Wangensteen’s Department of Surgery beginning somewhere in the ‘50’s, certainly ’51 was the first clinical attempt. I think that has always been of interest to me because, as I look back, there seems to me far more large numbers of institutions which were far better equipped in terms of having worked on the problem longer, perhaps the staff were more experienced and prestigious, particularly some of the universities in the East. People have often asked why did it start at Minnesota and I think that probably, as I look back, there are two basic reasons. One is – we had excellent facilities in the sense that the world’s first heart hospital was built there and opened its doors, actually, in March, 1951. That certainly was a stimulus because they had set aside eight beds out of 40 (20 children, no, 40 children and 40 adults) so 80 beds had been set aside essentially – 10 percent—eight of them –(four children and four adult beds) for heart surgery even though heart surgery at that time was essentially limited to lesions outside the heart: patent ductus, pulmonary stenosis and, of course, some of the more bolder surgeons were putting their finger in to dilate the mitral or pulmonary valves.
The other was, I think, the presence of Dr. Wangensteen as Chairman, Department of Surgery, because (but we don’t have time to dwell on it here at any length), he was truly a visionary person, not a cardiac surgeon but had some aspects of his training program, I suspect, and his outlook on surgery that certainly facilitated the type of work that had to be done in order to develop some of these things. Basically, I refer to the fact that he had an unusual knack of spotting talent in people who didn’t even know they had any talent at all. And, many of those people that he selected as residents were rejects from other places because they didn’t fit the conventional mold of a surgical fellow. But, in Dr. Wangensteen’s eyes, they had some particular thing that he thought was very favorable to surgery. The other thing was that following World War II, of course, a large number of young surgeons returned from the Army (as did I and others that I am going to mention in a moment) to take residencies or to finish them if they had already started them. So, by 1950, he had gathered a relatively large number of young, ambitious, aggressive surgeons that were all trained in his mold, you might say, and basically that was that there was no problem that couldn’t be solved if you didn’t – if you were not unwilling – if you let your imagination proceed freely and, secondly, the only other limitation on solutions for problems, other than utilizing thinking processes and imagination, was your limitation on knowledge. And, he was a very firm believer that where knowledge was lacking, it could often be rapidly broadened in the experimental laboratory by appropriate studies. So, in that milieu I think it’s not surprising that some of these things developed rather rapidly.
The next very significant development was on September 2, 1952, and I think that is an important date in historical assessment of open heart surgery because on that day Dr. John Lewis, who happened to be a classmate of mine, a very close friend and buddy in the Army – we had returned to take residencies together. He had worked on the problem of – he was interested in the problem of heart surgery as well. He had done a series of experiments in hypothermia with dogs stimulated by the work of Bigelow in Canada. In fact, we had sat together in 1951 when Bigelow presented his work and I recall it well at the American Surgical in Denver, right outside of Denver where they had the meeting – it’s that big hotel
WGR: Broadmoor?
LILLEHEI: Broadmoor, right, and John had said to me that sounds like a great technique, and going back in the next six or eight months to work out the techniques. By September of 1952, he took a young Minneapolis girl (I think, appropriately enough, named Johnson) who was about five years old and by this time the pediatricians were getting a little better. She had an atrial secundum defect exactly as planned and lowered her body temperature to 26 degrees centigrade and occluded the caval inflow in a period of about 10 or 12 minutes sutured up the atrial secundum defect; heart defibrillated nicely and took over and she made an uneventful recovery. I believe that is the first successful open heart operation in medical history. Of course, word of that spread very rapidly throughout the country and the world. At that point, I guess you might say heart surgery moved from the laboratory, at least partly, into the clinical setting and two to three cases a week were being done. And results, even in those early days, were excellent when the diagnosis was correct. But, whenever a ventricular septal defect was operated upon, either by design or by accident, (and, of course, some AV canals were operated upon) and a few tetralogies were attempted particularly, infundibulectomy more than trying to close the ventricular defect. Patients all died. So, it gave excellent results for atrial secundum defect, particularly the congenital, but a few acquired, too, were operated upon successfully. So that experience, while a great stimulus, reiterated again I think what was well known, in a sense, that perfusion method was really necessary to give more time for these more complex defects.
Well, at that time, to go back to Minnesota, we were working in the laboratory on this problem of trying to devise a perfusion method but we had no heart-lung machine because Dr. Dennis had built this machine, raised the money and, of course, had taken it to New York when he moved. So, we were using the method that we never dreamed that we would want to use clinically but which worked exceedingly well. And I suppose I ought to say at this point that how important sometimes a very simple observation can be in unlocking what seems to be a very difficult problem. I am speaking now of what we call the azygos flow factor.
Working in the laboratory, one of the residents working with me at that time, Dr. Morley Cohen, who is now Professor of Surgery at Winnipeg, was testing the tolerance of dogs’ vital organs (but particularly the brain) to inflow occlusion because, back in that time, we had a general idea but really didn’t have too accurate data on just how long a dog’s brain would go with inflow occlusion at normal temperature and various degrees of hypothermia. He noted that when he was a little bit careless and looped the superior vena cava proximal to the azygos vein and occluded at that point and then occluded the inferior vena cava inflow at the point of entrance to the heart, the dogs would go 30 minutes and wake up and be perfectly normal at normothermia. That was amazing to all of us because the azygos vein is rather small, as you know, particularly in a dog. So we measured that flow – just took a condom and cannulated it for 10 seconds to take the flow and we found that the flow that those dogs were surviving on was 8-14 cc per kilogram per minute. Well, that was revolutionary to me and I knew the moment we saw that, that this was going to simplify something. I didn’t know what but if we didn’t have to pump 100 cc a minute certainly we must be able to do something. I well recall showing that to Clarence Dennis, who is a very good friend of mine, and he looked at me like I had a frontal lobotomy because the feeling was, as I had felt, (and all of us in that field had simply accepted) that you must pump the basal cardiac output.
Well, with that knowledge, we decided first that we would devise a method with a simple little pump (a sigmamotor pump) and use the animal’s own lung or part of it. And that worked well as far as perfusion, but whenever we tried to work on the heart it would kick the venous return out of the lung and, bang, in 10 seconds the lung would be edematous and school would be out for that dog. So, that obviously was not going to work for heart surgery, at least at that state of knowledge. Somebody asked why don’t we just use a donor dog and cannulate down in the groin (saphenous vein or femoral vein in the dog) then the artery and we will use a low flow of 10-12 cc per kilogram per minute. We’ll use the same little pump (the sigmamotor) and the advantage of a sigmamotor was that it would pump both directions at the same time because of compressed tubing externally. We started using that just to open the ventricle of dogs and sometimes we made a ventricular defect and other times we just left it open (the ventriculotomy, open) for a period of time and then closed it. We made a ventricular defect and then we would close it. At any rate, it was obvious from the experience that I had had observing Dr. Dennis’ work that after, oh, probably 50-75 dogs, that this was a tremendous method. We were getting superb recoveries, far better than we had seen with the heart-lung machine not only with the number of the animals but in the rapidity with which they recovered from this procedure.
So by early 1954, we felt that we simply had to try this because, from the work of Dennis starting in 1951 with the first heart-lung machine attempt by extracorporeal circulation using the heart-lung machine, by that time, 1951 through 1953, there had been about 20, as I recall, open heart procedures done around the world. Crafoord in Stockholm had done several. Borema in Amsterdam was another pioneer at that time. Dogliotti in Milano had done a lot of work. All of these men had developed their heart-lung machine in the experimental laboratory, as Dennis had, to the point where they were confident of it. They wanted to apply it clinically. In addition to those I mentioned in this country, there was Helmsworth in Cincinnati, that I recall, and Dodrell in Detroit and, of course, Gibbon in Philadelphia. Of those 20 operations, the only one that the patient ever recovered from was in May of 1953, as I recall. This was Dr. Gibbon’s operation with his heart-lung machine, quite familiar I think to all that worked in this field. That was a 15 or 17 year old girl who had an atrial secundum defect and she had an operation by a screen oxygenator and made an excellent recovery.
And that very important event though provoked relatively little notice, as I recall, at that time for a couple of reasons. First, I suppose was the fact that by that time a number of centers, including Henry Swan in Denver, had taken up hypothermia – I think he had already been working on it before he heard about Dr. Lewis’ work and, of course, successful operation. Other people around the country were repairing atrial secundum defects with excellent results, as I said – around a 90 percent success rate for atrial secundum defects. And, secondly, I suppose was that Gibbon tried three more operations, as I recall, and none survived; so Gibbon unfortunately was quite disappointed. I spoke with Mrs. Gibbon just earlier this year and asked her that question. And she said he was a very sensitive person and with four deaths he felt that he did not want to go on. So he never did another heart operation. At any rate, throughout the world and the people that were working in this field, it was a feeling of pessimism which we all shared in that open heart surgery was a great concept, obviously needed. Tremendous things could be done if you could stop the heart, open it up, empty the blood. But this was probably going to be of limited value because how could you expect a sick human heart ravaged with heart failure and disease, tremendously hypertrophied and dilated, to withstand a major operation and a cardiotomy, incisions into the wall, stitching and cutting within it and then repairing to take over and support the patient. And it seemed very logical because, as I said, all of these people I cited a few moments ago who had been pioneers in the clinical application of the heart-lung machine have had excellent results in animals but, when they returned to human, they had had failures, one exception I mentioned.
And it seemed that the heart-lung machine was not at fault. Of course, there were problems of diagnosis and some of these others, but other cases were correctly diagnosed and did not recover. The atrial septal defects were doing well because those patients were not really nearly as sick as some of these other patients where it involved the ventricles and the valves. So, that was the feeling in early ’54 and I guess we shared in it. But I guess, fortunately, we did not necessarily believe it. And, again, Dr. Wangensteen was a tremendous help. He came over to the laboratory one day, as I recall, and saw one of these cross circulations in a dog. Anything new and innovative had a great appeal to him and he was enthusiastic about it and, without his support, I certainly would never have been able to do it because we started to look around for a patient and word did get out in the hospital that we were contemplating, (by saying “we” – that Morley Cohen was working on it as I have already mentioned; Dr. Herbert Warden was a resident at that time;subsequently or presently he is Professor of Surgery at the University of West Virginia; Varco, who was a staff man and interested in cardiac surgery, was doing the Blalock’s, ductuses and so on at that time). And we managed to interest one of the pediatricians who had a patient who was about 15 months old who had been in the hospital for some six or seven months. Usually they sent those kids home to die if they didn’t have a ductus or coarct because there was nothing else to do, but this patient kept getting severe pneumonia and not dying and coming back and, I guess for several reasons, Dr. Anderson felt that he might be a candidate for this rather radical procedure. And we proposed, of course, using one of the parents as a donor because in all children( who are legitimate at any rate) one of the two parents will have the same blood type.
We did find a few exceptions in our subsequent studies but, at any rate, in this case the father had the same blood type. We talked to him and he was the donor. So, on March 26, 1954, we undertook this operation for ventricular septal defect in this very sick infant. And things went rather well – it was a large defect and, of course, we sutured it up rather than use a patch, and the child came off the pump, woke up, and did rather well for 14 or 15 days and then he got tracheobronchitis (he had atelectasis before the surgery, of course, with chronic failure) and we lost the child, I think, about the 18th day. But at autopsy we were very encouraged because the defect was about 90 percent closed with stitches even though it was a large membranous defect. And,again,the child did not have heart block, which was one of the other things that people had predicted with ventricular defects since the bundle was know to run, even at that time, in close proximity of the membranous area that they would all have heart block. So, even though the child died, we were rather encouraged and, although there was a lot of opposition within the other departments in the hospital, particularly medicine and pediatrics, Dr. Wangensteen insisted and supported us to go ahead.
So in early April (about mid April) was when this child had died – a day or two after the other child had died – we did the unprecedented thing, I guess, of scheduling two cases in three days – ventricular septal defect by cross circulation. The reason that was done is Dr. Wangensteen suggested it probably would be a good time to do it because the superintendent of the hospital was out of two and a couple of other key people and that is what I mean by the support that we had from him. Fortunately, both of those made an excellent recovery. Both had membranous defects and cross circulation went smoothly and we were obviously thrilled. I think the important thing of that was that it was immediately evident – both of those were infants, one a girl and one a boy – that the “sick human heart” theory was just not valid.
So, with that success, obviously we started doing these patients two a week and that was a pretty good load, sometimes three because of the logistic problems of having to arrange for the donor. The only requirement on the donor really was that they have the same blood type and be in good health; although the strain on the donor’s heart was very insignificant because, again, we were pumping 10-15 cc per kilogram of body weight with these infants. These early cases were all infants (most all were under the age of two) and the pump, of course, did the work of circulating the blood. The dangers to the donor were really essentially, and they were well cognizant of it, first some kind of mismatch on the blood. Secondly, some imbalance and even though the sigmamotor pump it was rather easy to get imbalances because even with that low flow which, of course, if you tried to do a high flow it would have been a disaster. But a catheter could get against the wall of the vein and things like that. So we had to be very careful of that.
The third danger, I think, was air embolism which we had seen in the animal but fortunately never saw it in the human or didn’t see it. But knowing the hazards, I guess, was good reason to know how to avoid them. At any rate, we went ahead regularly then at two or three a week with ventricular defects and by August of 1954, I think, we were ready (by July, actually, the first one) we were ready to try in addition to one of these atrioventricularis commonis (atrioventricular canal) which had really been the bane of the surgeon because they were so terribly complex. Well, our first one was again correctly diagnosed by this time – it was an infant and it was a complete canal – and whereas we did pretty well getting this repaired, the child had heart block and lived for about 12 hours and then succumbed. The next one was an infant that John Keith sent us from Toronto Hospital. He is a very well known pediatrician in Canada and he had heard about the success for the ventricular defects and he had this girl, 15 months old, as I recall who had very severe failure and they were having great trouble keeping her alive. He had diagnosed an atrioventricular canal and called me up. And I said, “Certainly, we would like to have a go at it”.
Then, on August 6, 1954, we operated on that little girl and she was our first success. She made an excellent recovery and actually was recatheterized once about three months after surgery and once again about 15 years after surgery, (20 years, I guess it was) when she was pregnant to make sure that she would be able to tolerate the pregnancy. She had complete closure of her defects and mild regurgitation. I hear from her frequently. She has had several children now and has done well. Well, that was a great stimulus and, again, we really had in the back of our mind from the very beginning the tetralogy problem because I felt, at any rate, that the tetralogy was basically a two-fold problem - a ventricular septal defect and pulmonic stenosis – and we did something that I think was very important at that time. We had been doing it even before this first successful ventricular defect and, that is, having the diener in the autopsy room call me or one of the team or all of us anytime they had a death in an infant. We would go down to the autopsy room and, of course, I think it is the same in many universities, most autopsies are done late at night and done by the residents- the professors are never around. The resident didn’t care. We would look at the heart and if it had a defect we could operate on it right in situ under a dry field and we had probably a half-dozen over the year and a half or two years that we were doing this a variety of defects – ventricular defects, tetralogy. The tetralogy, I have some early pictures that we took after we repaired it. It was ridiculously simple in those infants, we thought, as opposed to looking at a tetralogy in a formalin jar where things were thick and stiff like shoe leather which, even today if you looked at it, you would say they were not reparable.
So, with that background, we felt we were ready for the tetralogy. Here again it was a more controversial thing because the other defects I’ve spoken about – none of them had palliative procedures at that time. Banding was unknown. Tetralogy, of course, had an excellent palliative procedure – the Blalock operation started, I think, in 1945. This was ’54. But, at any rate, with the support from above, we were able to obtain a patient from the pediatricians. I must say that the two young pediatricians, Drs. Paul Adams and Ray Anderson, were extremely helpful. I operated on that child on August 31, 1954 and, fortunately, that one was a complete success. There was no problem with perfusion and the child was recatheterized some months later and had complete closure and a 10 mm gradient, as I recall. And had that first one failed, we might have had great difficultly because many, even in our own department, didn’t feel that we should operate on a tetralogy when you had such an excellent palliative procedure. But, the feeling was that this operation was corrective and whereas it might (and actually did) have more risk in the beginning, certainly like any other operative procedure, we should be able to reduce the risk as we learned more about it. There were ten tetralogies done by cross-circulation and six survivors, four deaths – which was 40 percent mortality. As high as that was, it was not tremendously higher than the 15 percent or so that was present with the Blalock at that time and, of course, if they had a Blalock obviously they had to look forward to something corrective later if that was going to be possible
So, in that first year from March 26 1955 to early April 1955 (’55 or ’56) we did 45 of these cross-circulations. I think 27 of them were for ventricular defects and 19 survived. Sixteen of those 19 were under the age of two and I think it is important to point out here that we were not able to do that good in infants for the next several years with the bubble oxygenator, which I will touch on in a moment. You know it is obvious that this method had some fortuitous advantages that we didn’t fully appreciate at the time, although we did realize that such things as acid-base balance and so on were taken care of automatically, you might say, by the donor. And, of course, nobody knew anything about potassium in those days and all those things that came later. And they were all taken care of for us. So, it was obviously a great boon. About midway through those 45 operations, actually a young resident joined us named Dr. DeWall, whose main training, I guess you might say, for heart surgery was that he was very interested. He was a general practitioner in Anoka, Minn. and he was very unhappy with that. He had been there about a year and at that time we thought we needed an extra hand because in the operating room Dr. Cohen and Dr. Warden usually took care of the donor. Dr. Varco and I operated on the patient and we had to have someone to turn on the pump and so on. We found that after awhile if we put a reservoir in the venous line of the pump that things worked better so far as occlusion of the cavas. We couldn’t really depend upon the anesthesiologist to do that, so Dr. DeWall was taken on to do that.
In the meantime, as I say, there were two or there cases a week. His assignment was to work in the dog laboratory and I felt that the one that we had done some work along actually even before cross-circulation of bubbling oxygen in the blood and it was clearly evident that was a marvelous way to oxygenate blood. But, of course, at that time I think it was a universal agreement, if you talked to anybody who was knowledgeable in the field, that the one oxygenator that would never work would be the bubble oxygenator because it would destroy the brain. Well, about that time Dow Corning developed antifoam (Silicone A) and that was a marvelous substance for reducing surface tension and getting rid of bubbles and seemed very innocuous to the blood and I guess that hundred of thousands of clinical tests it is relatively innocuous as far as exposing it to blood. But that alone did not get rid of the bubbles fast enough, even with these low flows that were running. The oxygenator that was devised then between Dr. DeWall, who was working on it, and me, Dr. Cohen, and Dr. Warden was a simple bubble oxygenator which took a black rubber cork and put about 25 hypodermic needles through it and through that the oxygen passed and met the blood coming up through the center of the cork and it was never, as I said, any problem with oxygen/CO2 exchange.
Then that would go up this mixing column or bubbling column and across which it would first meet the antifoam when it crossed over towards the reservoir and then I think the important innovation that really made the bubble oxygenator safe and feasible was the idea of using a spiral coil – helix, if you will – in the reservoir. What that did is the bubbles that weren’t debubbled by the silicone antifoam-A in the exit from the bubbling column would go into this reservoir and, because it was a spiral descent, the bubble-free blood, of course, would be heavier and the bubble-containing blood would continually be forced to the top. So, we had the forces of gravity working on our side as long as we had a minute or two – whatever the flow was, you needed a minute or two – quantity equaled to a minute or two of flow in order for that process to work. We started using that simple bubble oxygenator in March of 1955 and we still used cross-circulation for about another month on what we felt were the difficult cases as hypertension and things like that. Then, in that transition period, we used both methods. It was evident that the bubble oxygenator which had, as I said, (I guess it was not evident to us immediately) but not having quite as good results, at least it freed us from the vexing problems and certainly the responsibility of the donor as well as the logistic problem and, of course, some patients did not have donors. Of those 45, I think two or three had people who volunteered to be their donor.
Fortunately, there was no mortality or morbidity in the donors of those 45. So, by March and April of ’55, the bubble oxygenator was working well and work continued. By that time a young fellow who was an intern on our service named Vincent Gott had joined the group. He was very interested in the heart and he went to the laboratory in ’55, ’56 working with the rest of us – Gott, DeWall, Cohen, and Warden. Our goal was to make this oxygenator as simple as it was and disposable, as it was something that could be fabricated and not have to be put together. By 1956, what we call the sheet oxygenator was perfected and working quite well and we patented that at that time and gave those patents to the University and they licensed Travenol to make it. Travenol did an excellent job of putting this unitized oxygenator together, shipped it out in a box all sterile and ready to go. This had an explosive effect on open heart surgery. There weren’t too many places that did cross-circulation but at the time the oxygenator came around, get a simple thing that they could hang up, fill with blood, and start going of course, as I said, that had a tremendous effect.
In the meantime, I should mention whereas Gibbon had given up completely at work with his oxygenator, Dr. Earl Wood, the physiologist at the Mayo Clinic, who was also my instructor in physiology, working with Dr. John Kirklin, had taken over this design. By March of ’55, I think, they did their first successful operation with the Gibbon oxygenator. So, then we had two types of oxygenators. Of course, there was still great concern to anyone who lived through that period or even reads about it with the bubble oxygenator, but I guess the times solved the problem as far as its efficacy. Actually, by 1963, another young fellow in our group who was working on this, named Arnold Lande was assigned the problem of developing a simple disposable membrane oxygenator. We thought that maybe that would be better than the bubble. He did a superb job but actually we learned more about the membrane oxygenator and I guess it took two or three years before I realized that actually we were not getting any better results from the membrane than the bubble. When you started to think about it, we realized that the large foreign surface of the membrane was as damaging to the blood as the bubbles. And I guess things haven’t changed too much today. The bubble oxygenators of today, with more knowledge, have evolved and learned how to reduce the oxygen flow and so on, and they have become very efficient.
I suppose the last thing( let’s not make this too long) the important byproduct of open heart surgery that I think is significant was the development of a new treatment for heart block. Now, as I mentioned earlier, it had been predicted by some of the pessimists that every single patient with a ventricular defect of any size or tetralogy would end up with heart block if we were able to operate on them at all. Fortunately, that pessimistic prediction was not totally valid but it wasn’t entirely invalid either. In these first patients that I mentioned through ’54 and ’55, about ten percent of the isolated ventricular defects or the tetralogies developed complete heart block, as we knew very little about really how to avoid it. We knew nothing about how to avoid it at those times. That doesn’t sound so bad, except in the first six patients 100 percent died. Ten percent of the first 60 developed it, but all of them died. What we were using at that time, of course, was the conventional treatment. Heart block was thought to be a rare phenomenon under any circumstances and very few people knew much about it or had much experience, but what little was known was that Ephedrine, of course, Epinephrine, obviously to keep the heart rate going faster would be a benefit, and Atropine had been recommended.
We used all of those drugs, as I said, with no long term success. Some of them we were able to keep alive for a week or ten days or even two weeks, but eventually we lost them. We heard about the treatment that Zoll was using in Boston for cardiac standstill in which you put electrodes on the chest. And he said you could stimulate the heart at standstill, and indeed you could, but it took about 50-75 volts of current and that is very painful. Of course, if applied repetitively at 70,80, 90 times a minute it was very uncomfortable for the patients and even in these infants where we were able to restrain them so they couldn’t rip these electrodes off, then we would get ulcers, infected ulcers, and we didn’t save any long term with that either. About 1955, as I recall, a new drug for asthma came on the market called Isuprel (or isoproterenol). It actually was used as a powder. I remember when we used to have to weigh it out and dissolve it, but it had an excellent chronotropic effect on the heart. And with Isuprel (it was also longer acting so we didn’t have the volatility of Epinephrine and Ephedrine where the blood pressure would be zero at one minute and 300 the next minute with an intravenous drip) I think we saved 54 percent of the next ten or so heart blocks and, with that, we made an important discovery (at least it was important to us at the time) that about two-thirds of them reverted to sinus rhythm if we could keep them alive a month. If they didn’t revert by a month, they were permanent most of the time and that was another problem. So that was a step forward, but we were still working in the dog laboratory. It was kind of a crash program to do something with heart block.
One of the residents assigned to that problem and worked on it full-time was William Wehricks. We tried other drugs too, but none of those worked very well. This electricity, of course, was uppermost in our minds and the idea occurred, “Well, why not just put a simple wire into the heart?” and fortunately in the dog you can produce heart block very easily - you don’t even need a heart-lung machine – inflow stasis and a stitch, so we had an excellent experimental preparation. And with the wire into the myocardium, it didn’t even have to be insulated. We found that 5-10 milliamps, or 1-2 volts, would control the heart rate perfectly in these dogs. I think within a week of that discovery we used it on our first patient, which was January 30, 1957. It was a tetralogy patient. We put a wire into the heart. We had no pulse generator of the conventional type. We had borrowed a Grass physiological stimulator from the Department of Physiology and that was the thing they used for demonstrating to medical students the effect of electricity on nerves, glands and muscles, etc. You could set your parameters for rhythm and current output very easily. That worked well, but it had to be plugged into the wall and, of course, that was a very severe inconvenience. On the patients who got heart block in the operating room, we had to string cords down the back to get them back to their postoperative recovery room. If they had to go for an x-ray or anything – again, string cords. We also were cognizant of the fact that, when it happened in the dogs, we could electrocute somebody with that arrangement. So, I had an idea that we ought to have a little box for the battery as our current requirements were very small – four or five volts at the most. There was a physics student who was working in our laboratory named Robert Russ, as I recall. He seemed very smart and very alert. He was always going to make this, but four or five months went by and we were still using this Grass stimulator whenever we had a block and nothing ever evolved. He was a graduate student, had no office and he lived in the dormitories. You could not call him. Whenever I would run him down he would say, “Well, everything is coming fine. The parts are on order”, and so on, but nothing ever happened.
So one day, Earl Bakken, a fellow that was a bright young electrician then, used to come over to the hospital but he did not work for the University. But he would come over because some of the equipment in the operating room, like the Sanborn recorders which he had a franchise to market here, the hospital electricians did not understand them so he would come over and fix them. Sometimes we would sit around and talk. I took him down to the laboratory and showed him what we were doing. I said, “Earl, we need a little box with a battery in it”, and so on. Well, in about four weeks he came back with the first pacemaker, a little square box at that time with the battery and the transistors had just come on the scene within that year; otherwise, you had to have some tubes, I guess, something like that. But that made it even more feasible. Well, that worked tremendously well and the patients could put this in their pocket and, of course, this completely changed the outlook. Bakken, at that time, had a TV repair shop in the garage behind his home and we have all seen those pictures – you might see them in a museum – in which he made these and, of course, other people who were operating who had problems with heart block would refer them to Earl. That was the start of the Medtronic Company, which has been quite successful over the years.
And, of course, then the next major step was the idea of Greatbatch and Chardack, of putting this type of thing under the skin. Well, I think that is irrelevant. A lengthy summary of some of the early days.
Jerry, if you have any other questions, I would be happy to elaborate on them.
WGR: Dr. Lillehei, I really appreciate your comments and you have taken us through that period just in exactly the way that I hoped you would. I do have one question. Because the background that you portrayed points up a different time as compared with the present, now, it is almost as though we are in a great era of clinical application and, in speaking to some of my friends, you almost get the impression that there is nothing left to conquer. No more challenges. Is it really that or is it just that people don’t let their imagination run as freely as you did in your days with Dr. Wangensteen?
LILLEHEI: Well, I think it is some of both. I have two sons that are doctors and they both are surgical residents and I must say that I have looked around long and hard for a place that would have a training program like Dr. Wangensteen’s, but I don’t think it is possible these days with all the restrictions that have intervened, and one can argue with that at some length, I guess, pro and con. At any rate, I don’t really think some of those things probably could have been done in the present era of informed consent, FDA approval, and all of those things. So that’s part of it. The other is that I think in any radically new field, as open heart surgery obviously was, just as in brain surgery earlier, abdominal surgery before then, there is a rapid period after it’s known it can be done. In thoracic surgery, for example, are many developments of significance. Very important about new operations, new techniques, and new ideas. And then, after a few years, obviously there is a leveling off as the possibilities, you might say, of that particular technique are developed and refined and applied. So, I suppose you can look on for ad infinitum, at least in open heart surgery, that there is going to be rapid advances of the 20 years or so between the ‘50’s and ‘70’s, but certainly there are other new fields that need to be conquered. Obviously, there is plenty of room for improvement in open heart techniques and there are still some areas that we certainly have not mastered. I suppose you might mention prosthetic heart valves, although I am rather enthusiastic about the way that is developing.
The artificial heart, for example, has been stalled for 15 or more years. If you had asked me 15 years ago when we would have a good, implantable pump, I would have said within a couple of years. But here we are in 1979 and there is still a number of limiting problems and I think somehow that there must be a way to unlock that field, perhaps the way the azygos factor – the azygos flow idea – did for open heart surgery, because I really think that was a very significant turning point along with the fortuitous choice of using a donor at that time when we didn’t know virtually anything about how to manage the severe cardiac patients as far as electrolytes, acid-base balance, and things like that. I say “the young” because I guess, unfortunately, old professors don’t usually come up with significant new ideas. I suppose there is no absolute limiting factor but, the way it is, new ideas of significant differences usually come from the young investigator for obvious reasons. I think also, though, it is important in training programs that you have, if possible, (this may be an ideal that is not always possible) people in positions of authority who really have open minds. Everybody thinks that they have an open mind, or likes to think they have an open mind, but I think the human mind is particularly geared to see what is wrong with something when somebody presents you with a new idea rather than what is good about it. I think that is probably – it’s been decried and criticized – the way it is always going to be because not every new idea is good. Not every change is progress. I think the young investigator - and it’s unfortunate he is young because he is immature, he is inexperienced – he has a new idea that is easily destroyed by someone who’s authority or eminent scientist telling them, “Well, that is no good. It won’t work. It has been tried before,” – that type of thing. And I shudder to think how many brilliant ideas have been stifled in the bud by ill-advised criticism to a young person.
I say that is why I cannot emphasize too much why I think – I’m sure open heart surgery will develop somewhere, someplace but I think that it was a unique circumstance in Minnesota at that time with Dr. Wangensteen and his philosophy and his interest in new methods, new techniques, and his ideas. He often quoted John Hunter’s famous dictum to Jenner: “Don’t think; try the experiment.” And I think we could modify that for Wangensteen as not only, “don’t think; try the experiment, but think”. That type of philosophy is very important to the development of new fields that are radically different.
WGR: Well, thank you very much. This has been just a superb time. I really appreciate it. Thank you.