This is May 1, 1979 on the occasion of the 59th annual meeting of the American Association for Thoracic Surgery in Boston, Massachusetts. It’s a lovely day and a nice day to do something other than listening to scientific presentations. I am Gerald Rainer and we have the opportunity today to speak with Dr. Charles Hufnagel in one of continuing interviews with pioneers of cardiac surgery. I have asked Dr. Hufnagel to review some of the high points and the personal encounters that he had in his involvement in the early days of cardiac surgery. Dr. Hufnagel.
CH: It is always hard to know quite where to begin. I think that my involvement with the then non-existent area of cardiovascular surgery really began when I was a Cabot Fellow at Harvard. I was interested in surgical research and obviously really didn’t know what to do when suddenly I had that opportunity thrust upon me. But, I decided the first objective that I would try to achieve was to be able to anastomose the thoracic aorta because this had not been very satisfactorily performed in the past, although Alexis Carrel had made a number of attempts to do this. So, I embarked upon this as a potential solution to the problem of coarctation. Coarctation wasn’t really very well known in those days except as a pathologic entity.
WGR: What year was that, Charlie?
Dr. Charles Hufnagel
Dr. Charles Hufnagel
Dr. Gross couldn’t come over to the lab that day, so I said, "Well, you help me". So, with the help of this secretary, who we trained to scrub, that was the first successful dog that we had with anastomosis of the thoracic aorta - just putting it together - and that dog lived. But it was obvious at that point that there was a problem with paraplegia. Any of the dogs that had their aorta clamped for 15-20 minutes and the longer you clamped it the greater the percentage of paraplegia. And it was, at that point, that I suggested that we pack the dogs with ice and reduce their body temperature. And suddenly the paraplegia disappeared. I then did a study on clamping the thoracic aorta without doing anything to it for varying periods of time and demonstrated that the progression of the lesion with increasing time in dogs. In most of the dogs with paraplegia, we found it was the destruction of the anterior horn cells that produced it and that was the beginning of our interest in hypothermia and we applied it in this way. Once this had been achieved, the interest shifted to preserving vessels so that you would have them available, and Dr. Gross and I didn't do any more work together at that point, and I began to work with the freezing of blood vessels. I froze them in a mixture of carbon dioxide and alcohol in a glass tube and filled this tube with Helium under pressure to get better conduction than you get in the air. And so I established a bank of blood vessels for the animals first, and this was successful in the sense that the dogs lived and the aortas seemed to be relatively well preserved with, of course, the loss of the muscle cells and the replacement really with fibrous tissue.
But that was the beginning of a new era of thinking in blood vessel preservation. I did that then in humans and had a bank at the Brigham as early as 1946 of human vessels that were preserved for use, although we didn't use many. When I told Dr. Gross about this, I then had 10 dogs and, after a meeting of the Boylston Medical Society, which was a student group at Harvard, we sat out in the cold in the car and I told him about this and he became very excited about it. But, he didn't like freezing vessels, so he went ahead and went back to Carrel's old method of preserving them in a fluid of 4 degrees centigrade in tissue culture media. He was very critical of the freezing technique for some time after, maybe two or three years so he went back to freezing and by that time had built an apparatus for getting high vacuum. This was really a big deal and then we would seal the tubes with a flame torch to preserve the vacuum and those would keep for a long period of time. It was about that time that I went to Georgetown and continued the work there. Actually, prior to leaving Harvard, I had an associate, Felix Eastcott.
Eastcott came over and wanted to do some research in the lab and so he joined me with me in that endeavor and after I developed the drying process, which was after he left, (we were just freezing vessels when he was with me) I went over to London and set up the freeze drying technique for Eastcott and Rob, and actually we got some of this glassware and apparatus out of Sir Alexander Fleming's old lab. He had died in the meantime and his laboratory was temporarily vacant, so we used some of his old glassware. They actually became very active in that field and Eastcott, as you know, is still very active in the area of vascular work. So, that once we had some of the problems of preservation of vessels under good control, it became easy to attack the vascular problems and for replacement of vessels for either the atherosclerotic ones or trauma. And the preservation to my mind was the key to opening the door to really the clinically application. I had, however, in the meantime been very interested in synthetic vessels, too, and stumbled upon to the idea that a non-wettable surface. There were certainly evidence in the literature, as you know, that, for example, the blood transfusions, the paraffin, the glassware, and so on. Carrel had tried to replace the thoracic aorta in dogs as early as 1910 and had no success in this. All of the animals either thrombosed or hemorrhaged and so, up to that time, there had never been a real solid prosthesis that could be put into a vessel that would remain patent for a long period of time, even though many attempts had been made.
WGR: Did you have any anticoagulants at this time when you cross-clamped or did you just have to sew fast?
CH: Sew fast. We didn't use any anticoagulants and it is interesting that in all of the early work we thought that the use of anticoagulants was contraindicated from the point of view of the critical point of the test is, “could stop thrombosis without it?”. And so we did not use them. But because of the surface characteristics, I chose methylmethacrylate as the material that seemed to have some promise and actually machined most of the original tubes myself and polished them with jewelers rouge and all of the usual polishing agents and, when placing these into the thoracic aorta, the problem was basically hemorrhage from circumferential necrosis of the vessel where it was tied in place. At that point, we then devised multiple point fixations in which there were points of pressure and points of relief so that the blood supply to the distal end could be maintained beyond the point of fixation. That then allowed us to have a rigid prosthesis, which would stay open permanently in a high flow situation in the thoracic aorta. Once that had been achieved, it was obvious that you could modify that tube into something else, and all of these tubes had been placed just distal to the left subclavian artery. They were approximately one centimeter in diameter tubes for dogs. The idea of modifying it to a valve was apparent and, at that time that was the only material which we had that would satisfactorily function as a blood conduit in a viable situation. So, I started to modify the tube into a valve and used a myriad of designs, the tear shapes and bullet shapes and all kinds of moving types of valves-- hinged valves, and so on. I ultimately settled on a ball configuration. It had certain advantages because it would rotate and we thought that wear would be minimized. It was interesting that, even at that time, I made the balls hollow in order to try and adjust their specific gravity so that it was just a little less than that of blood, so that it would just begin to float in blood.
WGR: Was the ball made of methylmethacrylate too?
CH: Un huh. Everything at that moment was made of methyl methacrylate. It was very difficult to get anybody to make them. People weren't interested in, or weren't used to, working in the plastic materials with any precision. It might make signs or things of that sort out of them, so there was a great deal of work that I did myself and finally found a little company that would at least do something close to what you wanted. So we then made a hollow ball and fused it by heat and by rotating on a lathe the two hollowed out ends, putting it together again, and then making the outside. Then we made the cage in two pieces and fused them together because I was convinced that the smoothness of the surface was extremely important. So, we polished and polished and polished those surfaces and flared the ends to get the minimized turbulence at the ends, because that was where all the problems of clotting would tend to occur. And that was well recognized. So we managed that and continued to work on it from about 1946 until 1952 before I put the first one in a patient, as we were obviously very concerned that it would really work as well in the patient as it did in animals. We recognized that putting it in the descending aorta was only a partial connection of aortic insufficiency. But it was apparent that the amount of leak was tremendously reduced, so that it was a reasonable approach. I must say that it was with some trepidation that we approached the first patient. In the meantime, we tried to refine the design of the valve and work out the mathematics of it so that the area of flow around the ball was about 50 percent greater than the area of the inlet flows, that there was no drop in pressure across the valve. The middle part was left outside the aorta to get that additional space. The first patient was done in October of 1952 and survived. The valve made a rather horrendous noise and it could be heard easily if the patient had his mouth open because of the juxtaposition of the trachea. There were many refinements that went on after that which included switching to a hollow silicone ball and that ball was made of nylon, a hollow nylon core the next one. Again, the specific gravity was adjusted and the silicone rubber was fused under high pressure.
WGR: Was the indication for the operation on the first patient just pure aortic valvular insufficiency?
CH: Yes. At that time that we were doing these early ones, the sole indication was aortic insufficiency?
WGR: Were you pleased with the clinical response of the patient?
CH: Yes. The response was really fantastic and no one had ever seen anything like this at that time. Obviously it did not correct everything, but the patients that were chosen were patients who had severe disease. Most of them had a lot of angina, and had very big ventricles and heart failure and, in that sense, we would not consider them particularly good risks at the present time,although obviously we would do them with great ease and not be so worried about them as we were in those early days. But the dynamics below the valve were all normal and the head and arm pressures remained the same; they were unchanged. We recognized that there would come a time when we were going to put it in the normal position, interestingly enough. And we were sure that one could put the two valves in series without having to remove the first one. And, actually, I have done that many times since. The problem of aortic stenosis was not left untouched and we actually made a valve which we combined with the homograft and a rigid plug which we plugged into the ventricles and bypassed the valve and ran over into the aorta by using the homograft for the aortic end. In some we used the valve with the tapered conical (cut off ) cone base to put it right into the ventricle. In some, we put the homografts at each end and had an extra support outside of it so that in systole it wouldn't close off the homograft.
At that point I also suggested to Tom Donovan, who was working in the laboratory at that time, what we could do to get around the pulmonary valve. And we did that. The apical-aortic anastomosis, as we termed that bypass for aortic stenosis, still has a place with modifications and so on in hypoplasia of the annulus and of the aortic root. These developments led obviously to a new approach to the problem of valvular disease and demonstrated that you could have a moving prosthetic which was activated by the blood pressure and the changes in pressure, and would open and close very satisfactorily. We were then moved on to try to put this in the aortic position - in the subcoronary position. And we did this in animals. The basic problem seemed always to be that this was basically an obstructive valve because it had to move far enough into the narrowing part of the aorta that it was always a compromise as to whether you were getting excessive obstruction or not. And this, I think, was a deterrent to our moving to that position in patients, although we did it in animals for sometime and actually devised a number of designs using valve stops and so on and made these all out of methacrylate and silicone rubber- (the ball out of silicone rubber) and the cage out of (and these were open-caged valves) not really like the ultimate one that Al Starr used, and he used curved cross cages and we had open posts with little stops coming in. So as that progressed, we also became interested after Blakemore and Voorhees had done their original work with vinyon-n. We continued to move along in the area of arteries or prostheses for arterial replacement and we did not think vinyon was a very satisfactory material. So we moved quickly to Orlon ®, which after a lot of testing in the laboratory seemed to be quite satisfactory. Actually I think it was in 1953 that we began using these in patients.
WGR: In the form of valve leaflet replacement?
CH: No, this was in the form of tubes which we sewed up and made flat pieces of cloth sewed into tubes and we were using them in the abdominal aorta and in the large vessels in the upper leg - the common femoral or the iliac vessels. It was interesting that the problem of wear and deterioration was always one which concerned everyone. But the Orlon® never gave problems about deterioration the way nylon did and we have had followup patients for as long as 18-19 years. They had the original sewn grafts without any disruption of the graft. It was interesting, too, that the problem of wear in those original valves was virtually non-existent. And very recently we have managed to find, I think it was, seven patients who have had valves placed between 1954 and 1958 who still had functional valves without evidence of any leak in their prosthetic valve.
So that development of that problem of obstruction led us to work with the discoid - the free floating discoid - valve for both the aortic and mitral replacement because we recognized in the mathematics of the aortic root that if you kept the length of travel to a very short distance, that you stayed within the maximal diameter of the sinus of Valsalva below the normal narrowing of the aorta, which occurs just above the sinus. I always talk about the mathematics of the aortic root. In the normal, the outlet of the ventricle is "x", the maximal diameter of the sinus is "1.5 X" and right above it goes to "x" again. So that by keeping the travel of the valve for about five millimeters (five to seven millimeters) you could stay within that because the normal sinus is approximately 15-20 millimeters long depending on its size. But at that point, we felt we wanted other materials than methyl methacrylate for a variety of reasons and we began to use polypropylene. And by 1962, I guess it was, that we had developed a free-floating disc in a couple of forms - one with the cage which had cross bars on it and one with the completely open cage and little hooks to keep the thing from going - and started to use those both in aortic and mitral valve replacements in animals. And, then shortly thereafter, in patients.
So it was interesting that while I started out with the ball valve that we once had gone into the open heart things, I never used ball valves. I think that the ball valve was an interesting forward step in the development of valves but, that because of its size and its mass and the torque which it produces in striking the seat and other things, that reduction of the mass with a lighter material such as polypropylene, which was also very tough, had a great deal to offer and gave better dynamics. So that in the interval between that, we had been working with flexible inlets. Everybody had leaflets, you know, because it was simple to recognize that if you had an aortic valvular disease that you could make something that sort of looked like a leaflet and put it in there and it should work. Actually, very few of those leaflets really worked very well. There were those that were made of Teflon; there were some that some people used polyurethane and a number of other materials, pericardium of course, and untreated pericardium. We had gone through the tissue type of valve things in the laboratory and thought that they were not suitable for any human applications at that time and so we went to a laminated type of prosthesis which was made of polypropylene cloth impregnated with silicone rubber under high pressure. We made some leaflets with a reflex edge.
The edge of the leaflet was turned back on itself to go against the aortic wall and that was left open without any silicone rubber for the ingrowth of tissue. And these valves were difficult to place because, if you didn't place them evenly, obviously one got more wear than the others and it was apt to break down. So that went through several evolutionary stages in relation to the way in which the valve was made and basically it was polypropylene. Those leaflets were the only leaflets, I think, that really lasted for any significant length of time. I happened to talk to John Grow the other day and he had taken one out recently that had been in for 18 years before it failed.
WGR: These were either single or composite one, two, or three leaflets depending on what was needed?
CH: Yes that's right. That's right. And we did have it made as a tri- leaflet kind of arrangement, but it was really quite crude and, in general, we placed the three leaflets and, as time went on, at first it was one, then it was two, and then it got to be that everybody got three. But they were placed individually, in general, at that time. It was somewhat later than that, I guess in the late 60's, that we went to a really unitized trileaflet with a frame and that frame brought into focus the shape of the aortic root and the scalloped contour of the aortic annulus. And I think that was the first valve that really had that and actually now I think that many of the bioprostheses are coming to that shape because it makes it very easy to place and we used those unitized trileaflet valves and had the same kind of problems. After a time, a certain number of these broke down because of the inability to quality control the process so that the distribution of forces was exactly equal. This one was very easy to place, however, and you could put three sutures in each leaflet area where you would remove the leaflet in the annulus and one at each corner and that was it. And it would stay there and it would heal extremely well. So again, it was a matter of material fatigue in relation to the stress. The stress was equally divided. They've lasted extremely well. But this is another area.
WGR: If you could, could you describe a little more in personal detail the feelings you must have had that day-I believe you said it was in October, 1952- when you first implanted your descending thoracic caged-ball prosthesis for the treatment of aortic insufficiency?
CH: Well, as you know, we had had a long experience in the laboratory. We had great concern about clamping he thoracic aorta for a period of time that was longer than 10 minutes. We thought we should have a maximal limit of 10 minutes. In the patient, that was a little short, but the concern was 1) for the cord, and 2) with the problem of acute left ventricular failure in a patient that was already borderline, or barely, compensated. And so we made every effort to do it as quickly as possible.
And so, days and days before, I would go over and over and over and over in my mind and try to foresee all of the possible problems and to have a valve that had the proper fit because there’s obviously considerable variation in the aortic size. And all night, every night, I was operating over and over and over, thinking about this and I’m sure I dreamt of every complication that could occur. But, as we approached this time, I don’t think there’s anything more than that—that wasn’t a great emotional thing. I think you had all of the data that you could get and the time had come to move and you were going to do it. And, obviously, we hoped we would have the favorable outcome. And there was grave concern for the patient under these circumstances. And we talked to the patient at length and made sure that the patient understood what was going to happen. It’s interesting that the first patient was a woman in her 30’s with severe disease. It didn’t bother her about the operation because she was in such difficulty that she thought this was the greatest thing since the wheel. We could offer her the only possible means of getting rid of her problem. It was interesting that she got a job in the hospital after her operation. She worked in the X-ray department, I think, for 8 or 10 years, and then ultimately died of other problems not related to her aortic insufficiency.
WGR: How long was your cross-clamp time on that first case?
CH: It was about 7 minutes. We had a number of instruments to facilitate that. We had a holder for the valve so you could slip it in. We had made a holder for the multiple point fixation rings which slipped on and put the rings around while the aorta was still intact. You made your clamping. Cut the aorta. Used the valve holder to slip it into the aorta which had been triangulated. And then just closed the clamp and the multiple point fixation rings held that. And then at the other end, you clamped it. And as you did this, we filled the valve to get all possible air out of it. The cross clamp times in these patients could be, and usually were, extremely short unless you ran into some technical difficulty, really that you should have anticipated.
WGR: Dr. Hufnagel, thank you so very much for this fascinating interview. It’s just been absolutely superb visiting with you and we appreciate your time. We have enjoyed it immensely and we look forward to more comments and thoughts coming out of fertile minds such as yours. Thank you again.
CH: Thank you.
Publication Date: 21-Feb-2005
Last Modified: 28-Feb-2005