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© 2004 European Association of Cardio-Thoracic Surgery
The mid-century revolution in thoracic and cardiovascular surgery: Part 612 Avenue Villardin, CH-1009 Pully-Lausanne, Switzerland
1.1. Introduction According to the Greek philosopher's saying ‘panta rhei’, so do scientific and medical advances follow a continuous stream to new forms of perfection. Even though the advent of extracorporeal circulation is only one more—if important—wave on the river of Heraclitus. The possibilities of cardio-pulmonary bypass have been such that it can rightly be looked at as the climax of a revolutionary development. 1.2. Hypothermia Before that turning point when cardio-pulmonary bypass became available, hypothermia as the sole method for open-heart surgery was an extremely short-lived one, from 1952 to 1954. Moreover, the method was never very popular, initially too cumbersome (remember the surface cooling in a bathtub filled with ice water!) and limited to simple straightforward operations. Few surgeons had the daring, technical skill, and speed to be satisfied with the 6–10-min time span allowed for an intracardiac operation. Though rapidly abandoned in favour of the heart–lung machine, hypothermia continues to be an essential part of modern bypass systems in the form of the heat exchanger. Furthermore, the introduction of ‘cold cardioplegia’ in 1959–1960 really started the development of ever more sophisticated and time-consuming techniques. The history of this chapter has been described many times elsewhere. The names of three surgeons essentially are associated with hypothermia Wilfred Gordon Bigelow, the pioneer in extensive research on the subject, John Lewis in Minneapolis who successfully performed the first closure of an atrial septal defect, on September 2, 1952, and Henry Swan the leader in the field.Henry Swan, at the University of Colorado, carried out his first open-heart procedure using hypothermia on February 19, 1953. He ‘excised’ a stenosed pulmonic valve during a 7(1/2)-min inflow occlusion. Swan went on to become the surgeon with the greatest experience who, in the few years before the coming of cardio-pulmonary bypass, brought surgery under hypothermia to perfection in hundreds of cases with a very low mortality. The two names, Bigelow for his research and Swan for his surgical experience, will always be associated with hypothermia in cardiac surgery. A fourth man, Charles Drew, should be remembered for introducing ‘deep hypothermia’. Drew was first assistant to Price Thomas when I first met him, and he later succeeded his great teacher at the Westminster Hospital in London. He performed his first successful repair of an atrial and ventricular septal defect under deep hypothermia on January 29, 1959. 1.3. The pacemaker Another fundamental contribution of cardiovascular research to the well-being of patients (and business!) should be mentioned en passant. Bigelow and co-workers reported on a still clumsy pacemaker machine at the 1950 meeting of the American College of Surgeons. Paul Zoll, the Boston cardiologist, is known as the ‘father of the pacemaker’ as he reported the first successful clinical use of a pacemaker in 1952. Lillehei, in 1957, used a wire electrode sutured to the myocardium bringing it out percutaneously to an outside machine for pacemaker stimulation postoperatively. Ake Senning is credited with the first implantable pacemaker in 1958!As a personal post-scriptum to this chapter I might add that during my frequent visits to Toronto I had many discussions with Bigelow about his research on the famous groundhogs, a wonderful personality only 3 years my senior. Incidentally, he never found the substance or mechanism, which enabled the animals to survive in hibernating conditions during the long Canadian winter! I cherish Bigelow's personally dedicated copy of ‘Cold Hearts’ (1984) which tells the whole story with many illustrations and over 208 pages. I also knew Charles Drew when he assisted Price Thomas during my early visits to the Brompton and Westminster Hospitals, and in the 1960s when watching him during his operations under deep hypothermia. Of course John Lewis was still in Minneapolis when I visited Lillehei at the Wangensteen Clinic. There is an interesting story about the chief Owen Wangensteen, John Lewis and Lillehei in the book ‘King of Hearts’ by Wayne Miller. In 1953, when Lillehei was ready and in a hurry to start his ‘cross-circulation operations’, Wangensteen refused to give him the green light and wrote Lillehei the following letter: "My dear Walt, Your persistence surprises me. I did not say you should not do your case. I merely indicated that I thought it would be a nice thing to do, in light that Doctor Lewis (Lillehei's senior) having pointed specifically toward repair of interventricular defects, to let him do the first cases here... Friendly, helpful, interested, and sympathetic competition is good...". Unfortunately, the next two operations of Lewis for V.S.D. were fatal. Lewis was devastated and Lillehei was right that hypothermia was not the answer for a V.S.D. Thus, we arrive at the fascinating chapter on cross-circulation and cardio-pulmonary bypass.
1.4. John H. Gibbon (1904–1973) (Fig. 1)
John Gibbon will undoubtedly always be remembered as the man who, after 22 years of imaginative and persistent research, developed the first heart–lung machine to be used successfully for an open-heart procedure in 1953. His story is well known and has been told enthusiastically by his contemporaries Eloesser and Shumacker—great chest surgeons in their own right, intent on accentuating the merits of the man already in the shadow of Kirklin and Lillehei. Gibbon being of another generation than mine I never knew him personally, but when I started to attend the AATS meetings—as I said earlier in the back of the room reserved for visitors and ‘non-members’—I remember him well sitting in the front surrounded and respected by his peers, the great names of those days—Churchill, Graham, Blalock, Alton Ochsner, etc. In a recent letter, a Canadian cardiac surgeon, Anthony Dobell, who worked under Gibbon answered my question this way: "He was a wonderful mentor, a leading academic surgeon committed to general surgery and opposed to superspecialization. He was a remarkable surgical leader with remarkable knowledge of surgery and physiology. He could be called the father of extracorporeal circulation but not the father of heart surgery. His focus was the heart–lung machine and the one successful case sufficed for this purpose..." In summary, as the story is told, his interest in the problem started in 1931 when, as a research fellow of Churchill—he was not even 30 years old—he was assigned to ‘night watch’ a young patient dying and suffocating from a massive pulmonary embolus. In spite of the emergency embolectomy by his chief Churchill the patient expired in the morning. Gibbon himself describes his feelings: "During that long night's vigil the idea occurred to me that the patient's life might have been saved if some of her cardiorespiratory functions could have been temporarily taken over by an extracorporeal blood circuit". For the next 3 years, Gibbon was back in Philadelphia practicing surgery and only took up the idea again in 1934–1935 when he obtained another research fellowship with Churchill. From 1936 on he pursued this work at the University of Pennsylvania. During the Boston episode he married his research assistant, Mary Hopkinson, and from then on the two continued many years of research together. Charles Best and co-workers had just produced heparin in clinically significant quantities. Immediately realizing its importance for his research, Gibbon obtained a small quantity of the substance from the University of Toronto, and in 1939, at the meeting of the American Association for Thoracic Surgery, Gibbon was able to report the survival of four animals after bypass. Following an interruption of his research during the war years, Gibbon pursued his goal as Professor of Surgery, first at the University of Pennsylvania and later at the Jefferson University. The year 1946 was a decisive one for Gibbon. During a vacation he met Thomas Watson, the Chairman of IBM, who agreed to support the project financially and through technical assistance. This association apparently provided the needed breakthrough. In 1951, Gibbon was able to report on seven dogs surviving prolonged bypass, and on May 6, 1953, he performed the world's first open-heart procedure under extracorporeal circulation. His patient, Cecilia Bavolek, had a large atrial septal defect repaired during a 26-min cardio-pulmonary bypass. Following this epochal success, Gibbon lost the next four patients and abandoned all further attempts, an attitude that has puzzled many experts and was indeed criticized by some. It seems quite evident that Gibbon was essentially a scholarly investigator and not the aggressive type of surgeon like his Philadelphia neighbour Bailey. It may also be that at the age of 50 or more he had lost the drive to wrestle with the difficult problems of open-heart surgery. Be that as it may, Gibbon made a historical contribution in conceiving the first functioning screen oxygenator, the model for the highly successful IBM–Mayo heart–lung machine. John Kirklin had obtained Gibbon's authorization and had the machine perfected with the help of the Mayo physiology and engineering departments.
1.5. John W. Kirklin (1917–)
A few years later, commuting from Minneapolis, I joined the many visitors watching one of the two best cardiac surgeons worldwide, doing one difficult open-heart operation after the other. Still, maybe another 15 years later I came to Birmingham, Alabama, to find out about Kirklin's automated, computerized postoperative management of critically ill patients. I was never really close to John Kirklin, probably few people were. He was an imposing personality in the world of surgery, not only as a surgeon and researcher, but also as the long-time editor of the Journal of Thoracic Surgery. Nevertheless, I knew him well enough and in his reserved, somewhat aloof style he was always ready to answer questions or engage in discussions. I respected him most for all of his fairness and friendship toward his most important competitor Walt Lillehei—only 60 miles away. In 1979, in his Presidential Address, he paid Lillehei the following tribute: "He always was and still is a great hero of mine (!) because of his enormous ability and warm friendship. It is some cruel trick of fate that there is no operation called the Lillehei operation, yet he was one of cardiac surgery's greatest innovators and did scores of first time operations". It is indeed rare among physicians that one of them gives his unreserved praise to his immediate competitor: both pioneers could claim a ‘Kirklin procedure’ or a ‘Lillehei operation’. They were both unique and the living symbols of our mid-century revolution in thoracic and cardiovascular surgery. Actually, during almost two years (1955–1956) only two surgeons in the world—60 miles apart—performed open-heart surgery on patients, Kirklin and Lillehei. When I went to see them operate in preparation for our open-heart program—like so many young surgeons from all over the world—we had a very convenient regular limousine service from Minneapolis to Rochester and back, a facility we all used depending on the respective operating schedules in the two hospitals. However, before describing the fascinating saga of Lillehei's career I would like once more to come back to Kirklin, and quote his scientific resume as written by Marc Ravitch in ‘A Century of Surgery, History of the American Surgical Association’: "Innumerable technical and conceptual contributions to cardiac surgery. Early modified Gibbon's oxygenator. Consistently produced results matching or bettering others reported. It may be that his major contribution has been, using the operating room and intensive care unit as sophisticated laboratories to demonstrate the value of systematic measurements and construction of formulae and normograms to indicate when, in the course of a given cardiac lesion, operation is to be undertaken and which operation under which circumstances. Extended the concept and design of computer management of the patient to indicate automatically what was to be done, how much and when". Incidentally, the system obtained never gained general acceptance and during a memorable meeting of the A.S.A. (1969) Malony gave the opposing paper with the revealing title ‘The Trouble with Patient Monitoring’, a point of view underscored by the highly respected Francis Moore of Boston. In retrospect, Kirklin may have been ahead of his time... The man who was ahead of Kirklin was C. Walton Lillehei.
2.1. C. Walton Lillehei (1918–1999) C. Walton Lillehei (Fig. 3) was able to tackle the problem before everybody else for two reasons. First of all the Wangensteen Clinic had a very strong laboratory—research base and having himself obtained a PhD Lillehei was able to put together a strong team for the open-heart surgery project. In second place Lillehei strongly believed that ‘open-heart surgery should get out of the laboratories into the clinical arena’, and he had the background, intelligence and tenacity to make things happen. Nobody can and will deny Lillehei's outstanding stature as a determined surgeon–researcher with a vision and a purpose. Nevertheless, the first class team he was able to assemble played a crucial role in the ultimate success of the cross-circulation experiment and the assembly of the first reliable bypass machine, the famous ‘bubble oxygenator’.
Lillehei still worked in the laboratory when Morley Cohen (Fig. 4) joined him. Cohen was a young Canadian surgeon interested in training at the famous Wangensteen Clinic. According to the chief's principles he was first sent to the laboratory where he was attached to his senior Lillehei. It was while working together that Lillehei discovered the publication of Andreasen describing the low-flow azygos principle. Morley Cohen later, with another student Herbert Warden, performed practically all the animal experiments with the ‘azygos principle’ until he was ready to take cross-circulation to the operating room and follow up on human patients and donors. Richard DeWall (Fig. 5) only appeared for the bubble oxygenator. It was Dick DeWall who was the tinkering genius who, discussing the problem with his chief Lillehei, put together the amazing, still functioning contraption called the ‘bubble oxygenator’ allowing the Lillehei team to progress from cross-circulation to the very first ‘heart–lung machine’ functioning with DeWall at the machine in human case after human case. Richard L. Varco (1912–) grew up in very modest circumstances in a small town in Montana. He was Lillehei's senior by 6 years and was one of Wangensteen's first residents. He was involved in every stage of early cardiovascular surgery in Minneapolis. Among the first surgeons to perform the Blalock operation outside of Johns Hopkins, he early on reported enviable results with the blue-baby operation. He helped Clarence Dennis with his unfortunately unsuccessful operations under cardio-pulmonary bypass in 1951, and John Lewis with his first successful A.S.D.-closure under hypothermia (1952), and personally demonstrated the feasibility of operating for pulmonary stenosis under normothermic inflow occlusion. He encouraged Lillehei's work from the start and was his first assistant in all 45 cross-circulation cases. He was a somewhat taciturn, unemotional, highly intelligent, brilliant surgeon. His moral support and help certainly was an important factor in the ultimate acceptance of cross-circulation and consequently of Lillehei's career. To us, European visitors accustomed to rigid hierarchical rules in our university clinics, it was one more revelation to observe the generosity of the accomplished surgeon helping a young colleague.
Before starting my career as an amateur historian of our past I never discussed this important team-aspect of his success with Walt Lillehei, although I would have had many occasions to do so. Walt had of course many friends all over the world, but since our meeting as young, hopeful residents at a bar in Atlantic City in 1951—half-a-century ago—we had what the French call ‘des atomes crochus’ and remained lifelong friends. I do not compare myself to him, but we had the same determined attitude towards our profession. In 1956, 4 years after Atlantic City, Lillehei had already become the world-famous surgeon he was to remain all his life, the ‘father of open-heart surgery’. That spring, or early summer, we made a memorable tour through the South of France with our wives in what is today a vintage car, my black ‘Citroen 11 légère’ front-wheel drive. I want to tell this story only to throw light on the unique character of this man away from laboratory, patients, and operating room. Many years later, during his ‘retirement’, he described himself in an article, as a ‘skeptic at heart’. He never accepted a professor's authority and said "Questioning authority was one of the principal ways we made significant progress in open-heart surgery; once they said it could not be done it was a sufficient challenge to do it"—an attitude actually typical during the entire story of the mid-century revolution for all the actors. Lillehei had this unorthodox approach in small everyday situations as well, as the story of our French vacation will show. On a pleasant summer evening, at the end of a typical French dinner beside the river Rhône at Villeneuve-lès-Avignon, Lillehei's wineglass was half-full with an excellent Bordeaux wine when he started to fill it up with the remaining white wine we had at the start of the meal. In answer to my shocked exclamation that he could not do a thing like that, a ‘sacrilège’ to the French gourmet, he said in his quiet, somewhat smiling manner: "Why not? In a minute both red and white wines will mix in my stomach, anyway". As one can see, he believed in ‘heterodoxy’ and questioned authority in small things as in the most important problems! Arriving at the fascinating history of cross-circulation and the bubble oxygenator I would like to refer the reader to the many detailed histories written about this important chapter and only briefly review the essential steps from the laboratory to the operating room. Walt Lillehei's life has been so often written about in biographies, medical journals and newspapers that I prefer to concentrate my message on the significant milestones which marked his career as probably the most important pioneer in our field during our ‘mid-century revolution’. His life, like everybody else's was marked by ups and downs. The two most important intervals: his life as an army surgeon in the North African desert and during the battle of Anzio, and his ordeal with radical, head, neck and mediastinal surgery for a parotid malignancy, should be remembered. I think that they toughened his character to confront the tormenting decisions and responsibilities of his unique career. On the road to open-heart surgery I consider the key event being his coming across the apparently insignificant paper on low-flow physiology by Anthony Andreasen in the 1952 British Journal of Surgery. Only very few clinicians would have been alerted by the title or the essentially theoretical problem of laboratory physiology. But Walt Lillehei was, and immediately had his laboratory assistant Morley Cohen look into the practical possibilities of low-flow circulation for extracorporeal bypass. They named the phenomenon that an animal's brain survived with only a small fraction of the total blood volume, the ‘azygos flow principle’. As the saying goes ‘discovery happens to the prepared mind’ and, as Lillehei said, ‘the essence of wide applicability is simplicity’. The latter ‘bon mot’ will apply especially to the next step, the ‘Lillehei–DeWall bubble oxygenator’. Coming back, for the time being, to the azygos, the low-flow principle which simplified enormously the problem of cross-circulation in the animal experiment by preventing overloading of the donor animal's circulation. The ensuing laboratory work of Morley Cohen established every minute detail of the procedure. Of course Lillehei was intent on getting open-heart surgery ‘out of the laboratory into the operating room’. When he insinuated the idea of using this placenta-like cross-circulation between a patient and a human ‘donor’, Clarence Dennis (Lillehei's senior) thought "that I was some kind of a nut" and when later he presented the clinical series Willis Potts, the noted cardiac surgeon, ironically suggested that the author had just presented an operation with a 200% mortality risk. There is no question that at the time, coming from an as yet unknown surgeon, it was a momentous decision to bring cross-circulation ‘from the laboratory to the operating room’ and, as I said, his experience behind the World War II battlefields and his own battle with cancer gave Lillehei the kind of adamant strength of character to do so, and more so to go ahead with 45 consecutive cases on human patients and donors, correcting some of the most complicated congenital cardiac malformations. Undoubtedly the moral caution of one of the few very important surgical leaders, Owen Wangensteen, should not be underestimated. As I mentioned in an earlier chapter, another unexpected generous applause came from the highest authority, the man who had started modern cardiovascular surgery a decade before, Alfred Blalock. On April 27, 1955 Lillehei, still only a guest of the American Surgical Association, presented 10 cross-circulation cases for correction of complicated tetralogy and pentalogy. The discussion was opened by Blalock who said: "I must say that I never thought I would live the day when this type of operative procedure could be performed. I want to commend Drs Lillehei and Varco for their imagination, their courage and their industry". In closing the discussion Lillehei announced ‘a bright future’ for artificial oxygenator ‘but not for the complex types that have been described to date’. Just 16 days later after the A.S.A. meeting, on May 13, 1955, Lillehei made his prediction come true by the first clinical use of the ‘Lillehei–DeWall bubble oxygenator’. For the reader in years to come it might be interesting to reproduce excerpts of a reply Morley Cohen wrote to me on February 17, 2001, "As regard to Richard Varco's role in the open-heart story may I say he was a superb surgeon who blended unusual technical talents with physiology and science. The latter came to him from his position in the basic science physiology department under Dr Maurice Visscher. After the war the head of the surgery department (Dr Owen Wangensteen) ‘borrowed’ Dr Varco from Dr Visscher to boost the teaching capabilities of his own department, especially in surgical physiology. With the passage of time Dr Varco decided to make surgery his permanent career... Walt Lillehei felt that the complexity of the early heart–lung machines made the goal of safe bypass difficult to achieve. In early 1951 Lillehei, with Varco's encouragement asked me to work in his laboratory facility on this problem in particular". Dr Cohen then describes in some detail his intense experimentation with the minimal (azygos) blood flow, first with a model of oxygenation by part of the dog's own lung and, only following unsatisfactory results with this model, his passage to cross-circulation experimentation in the laboratory: "Dr Warden and I discussed this at length and considered such alternatives of a source of oxygenated blood as a placenta might provide. At this point the idea of using a second intact dog in which we cannulated the vena cava and aorta through the groin we were able to solve the problem of a controlled source of oxygenated blood for the test animal (returning an identical flow of venous blood to the donor animal). With this technique of cross-circulation we were able to carry out a second set of intracardiac operations and defect repairs with high survival and low mortality. Dr Lillehei joined us in the laboratory at least once a week, providing constructive suggestions... Finally, in early March 1954, the four of us carried out a successful repair in a young girl. This was followed by another 45 cases of a variety of lesions with laudable success and low mortality in the ensuing months". In the summer of 1955, Dr DeWall solved the problem of artificial bubble oxygenation utilizing ‘Antifoam A and a helical reservoir’. Eventually, Dr Cohen returned to Winnipeg and was appointed Professor of Cardio-thoracic Surgery at the University of Manitoba. As an author as well as a reader we should be grateful to Morley Cohen to have left with us this first hand report.
The extracorporeal perfusion of isolated organs, usually the kidney, was established by physiologists as early as the turn of the 19th century. As DeWall wrote in his excellent 1961 review on blood oxygenators, blood gas exchange is the same whether the ‘filming’ of blood runs over an air bubble or a metal screen. Most researchers, Drinker, Gibbon, Melrose, Kay-Cross, Crafoord and Senning were attached to the screen method. Lillehei, on the contrary—looking at the years of failure by Gibbon—considered the screen oxygenator to be too complicated and early on he opted for the ‘bubbler’. Once more the skeptic at heart made the right decision. He put one of his gifted men, DeWall, a 27-year-old general practitioner turned researcher, on the job of building a bubble oxygenator to be used instead of the cross-circulation donor. In the shortest possible time during the cross-circulation episode in the operating room, DeWall, in the laboratory, solved all the problems, the physiological ones, large versus small bubbles, as well as the practical ones, like the supposedly ‘Dairy Pump’ or the disposable polyethylene tubing used in a ‘mayonnaise factory’. Thus, within the year, Dick DeWall put together the key-element for the early open-heart surgery, the famous ‘bubble oxygenator’ which looked more like a gadget for kids to play with or more like a Model T Ford of 1913 (!) than Lillehei's Buick convertible (1955), certainly not like an up-to-date medical appliance. Be that as it may, the strange contraption worked perfectly for Lillehei and Varco and turned out to be the prototype for the commercially produced disposable ‘Helix bubble oxygenator’, the earliest bypass machine enabling most of the early teams all over the world to finally embark on unhurried open-heart surgery.
Half-a-century has passed. When I first came to Brookline, Mass.—today's vast hospital center—the place was still a quaint village and in Minneapolis, walking away from downtown in search of a steak restaurant or a bar, I soon found myself on an unpaved deserted road towards wide-open spaces of Middle America. Surgery has evolved from crude tourniquet lobectomy to total correction of tetralogy with the help of the disposable bubble oxygenator. One can rightly say that with the daring cross-circulation episode and the bubble oxygenator in Minneapolis, and the Gibbon–Kirklin machine at the Mayo Clinic our mid-century revolution had attained its (temporary) zenith. For 2 years, 1954–1955, there were only two places, two surgeons, Lillehei and Kirklin, performing open-heart surgery. Essentially, since the cardio-pulmonary bypass everything became possible and spectacular accomplishments by new pioneers were still to come. First the heart valves by Hufnagel, Harken, Starr and Lillehei himself, then the most spectacular explosion of aorto-coronary bypass, and finally transplantation by Barnard and Shumway—both trained by Walt Lillehei. The ‘condicio sine qua non’ still was cardio-pulmonary bypass. Today's historians as well as the leaders in our field should always remember that the all-important aspect in a surgeon's life is to pass on his trade from one generation to the next. Surgeons come and go. Most of the great surgeons I have remembered in these pages are already forgotten or soon will be. Very few deserve to remain household names like Ambroise Pare, Halsted or Cushing. The reader will have felt that maybe only two of my ‘heroes’, Lillehei and Kirklin, deserve a place in history to be remembered by generations to come. Be that as it may, names are unimportant as long as medicine and surgery perdure and other new developments and revolutions will occur. Panta rhei says the philosopher. As for the author of this review he can only feel grateful to the many surgeons and friends who made his life as a 20th century surgeon as fascinating as it was.
doi:10.1016/j.icvts.2004.07.002
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1. Open-heart surgery
2. Lillehei, cross-circulation...
