| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1997;64:1561-1563
© 1997 The Society of Thoracic Surgeons
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
Abstract
I recall the origins of cardiac surgery and the evolution of cardiac transplantation. Although the results of transplantation have been greatly improved during the past two decades, newer concepts and research offer the hope of an even greater future.
Because this conference is titled "Cardiovascular Surgery—Then and Now," I have taken some freedom in defining then. Then to me begins in the year 1945, when I first met and worked under William H. (Harry) Muller, Jr, at Johns Hopkins. He was one of four assistant residents, and I was one of eight interns. He was a standout even then, a quality that has progressively increased in the intervening years.
That was the year of the first blue-baby operation that was to become a signal event in cardiovascular surgery and in my life. Although I did not realize the significance of it at the time, on November 29, 1945, Dr Blalock performed the first Blalock operation, or "subclavian pulmonary anastomosis" as he called it. Two days later I rotated to the surgical service that took care of children in the Hariet Lane Home for Children (replacing Denton Cooley), and much ado was made of the little 16-month-old infant in an oxygen tent. Then there was not much one could do except use an oxygen tent, and that did not do much. There were no chest tubes, so repeated needle thoracenteses were used to remove the accumulation of pleural fluid. A needle was left in the intercostal space to relieve her tension pneumothorax. The little 4-kg child was tough, and she survived. Two other children underwent the Blalock operation in the ensuing months, and the 3 of them were reported at the Hopkins Medical Society meeting the following March and in the Journal of the American Medical Association in May. There was much acclaim as these pitifully blue, dyspneic children became pink and were able to be active.
Soon afterwards I left for the Navy, and while I was in San Francisco awaiting transport to the Philippines, the news media made much of a half-million dollar deficit reported that year for the Johns Hopkins. Then there was no Blue Cross, Medicare, or much state support, and the trustees were expected to find ways to make up this deficit without resorting to managed care, merger, buy-out, or affiliation.
A few months later, Harry Muller entered the Army just after the most important event of his life: his marriage to Miss Headly, Head Nurse of Halsted 5, also a standout, competent, attractive lady with a unique combination of professionalism and friendliness, who wore one of the most distinctive nursing caps. (Then nurses wore caps and white uniforms.) By getting married at the time of his departure, Harry escaped a clause in his contract with the hospital that prohibited changing one's marital state while a house officer. In 1944, just before graduating from medical school and after gaining the appointment as an intern at Johns Hopkins, I had informed Dr Blalock that I would like to marry and requested his permission. He wrote that in his experience unmarried house officers had been the better ones, but if I felt it necessary I had his approval. It turned out that Dr Blalock was very interested in and solicitous of the well-being of residents' wives and families.
When I returned to Johns Hopkins after a little more than a year in the Navy, about 200 Blalock operations had been performed. The usual schedule was for the chief resident to begin the day assisting Dr Blalock with the Professor's operations before taking care of his own operative load. Bill Scott was the only chief resident, and he was the busiest surgeon in town. He had already completed a residency at Children's Hospital in Boston and was looking for someone who could relieve him who would be dedicated to the heart service, dedicated in the sense of being expendable. I was that expendable assistant resident. It was my lucky break, for in the next 9 months of 1946 to 1947 I assisted Dr Blalock and other members of the faculty with another 200 operations, and was helped by Dr Blalock to perform a few myself. That laid the groundwork for my wife, Louise, and me to accompany Dr and Mrs Blalock so I could assist him while he was a visiting professor at Guy's Hospital in London. This was followed by a short stay in Paris. On the way over we traveled with Dr Edward P. Lehman, who preceded Harry Muller as Chairman of Surgery at the University of Virginia, and his wife. Traveling with the Lehmans bolstered my interest in and affections for the University of Virginia that began when, as a student at Davidson College, I made a couple of trips to that campus. I was a little jealous of Harry Muller when he was offered the Chairmanship at the University of Virginia in 1954.
Then, 1946 to 1949, there was little to do with transplantation but there were frequent thyroidectomies and not infrequent inadvertent parathyroidectomies, a disabling complication. Medawar had reported his early work with transplantation and demonstrated greater success with transplantation of fetal tissue. It seemed possible that fetal parathyroid tissue could be transplanted to some of the patients who had lost their parathyroids, so as a trial, Denton Cooley and I agreed that he would transplant fetal parathyroids from an abortus to my abdomen. I remember three things about that event. He removed one a month later and found nothing but scar tissue I presume the remaining one is nothing but scar tissue today. Mrs Sherwood, the humorless operating room supervisor who frowned on our shenanigans, had a bill for $64.00 sent to me for the use of the operatin room, which was four times my monthly salary then, and the pathologist sent me a report that the donor had syphilis. I mentioned this once when Denton was presenting his growing experience with transplants to the Southern Surgical Society, and Denton's comment was that "Now you know where Henry gets his mental aberrations." If you are wondering, the pathologist was joking.
The then in cardiac transplantation shifts to 1967, when Christiaan Barnard first successfully transplanted a human heart. The world was waiting for this event and use of the operation spread like wildfire. Transplantation of both the kidney and the liver had already been successful and served as a helpful guide, as it has subsequently, with the use of drugs for the management of immunosuppression. The operation as it had been developed by Shumway Lower is dramatic but not very difficult. More than 100 heart transplantations were done in 1968, with the highest incidence of 26 transplantations in November. You can recognize the pattern of an epidemic: first, a few cases that spread the germ and infected the world with the idea, followed by a quiescent period in which the germ was incubating and teams were tooling up, and then it spread like a full-blown epidemic. But immunity soon came in 1969, as everyone realized that although it was feasible to transplant hearts at that time, it was not reasonable to do so because of the imperfection of drugs used to fight rejection and the lack of skill in administering them.
Those were exhilarating pioneering days. We made our own antilymphocyte globulin from a pet horse we had on our small farm and used the children's thymus glands that we incidentally removed when the thymus interfered with exposure during repair of congenital heart disease. (This was before we knew much about the role of the thymus.) We performed only a single operation in 1968, but resumed our program in 1980 when Norman Shumway was encouraging others that transplantation had become practical results were getting better. The following year, 1981, Thomas Starzl joined us at the University of Pittsburgh and brought with him great experience and expertise with transplantation, which at that time was a bud waiting to blossom. Starzl had discovered how to use cyclosporine, and he was one of the few who had access to it for transplantation of kidney livers. He made it available for cardiac transplantation; at that time cyclosporine was still an experimental drug and its use was restricted. Our cardiac results were quickly improved with the use of cyclosporine. Equally important, when our procurement team went to procure a liver (Starzl was one of the few surgeons transplanting livers at that time), they often came home with a heart. On some occasions in those early days, we had a heart, a liver, a lung, and a kidney transplantation going on at the same time. Our experience grew rapidly, and transplantation became the most frequently performed operation at the University Hospital.
Our criteria for the selection of patients for heart transplantation were similar to those of most other teams. Patients must be severely ill with no other treatment available, have good function of other major organs, have no systemic disease, and have a very poor ejection fraction. The age limit of 60 years was not absolute; our oldest transplant patient was 67 years old, and she survived to 72 years of age. Fixed pulmonary hypertension was a contraindication to orthotopic transplantation but, in 17 instances heterotopic transplantation had been done in which the two hearts shared the load of pulmonary hypertension. I recall that the first patient with a heterotopic transplant was operated on 11 years ago is still well and active. She is a travel agent calls Bart Griffith from all over the world, extolling thankful for what she is able to do. In the selection of such patients, the use of prostaglandin, to reduce pulmonary artery pressure has been helpful. If the pulmonary hypertension is responsive to prostaglandin these patients can be nursed through the critical early postoperative period until pulmonary pressures become normal. Recipients of heart transplants must be free of significant other disease, drug addiction gross obesity diabetes and severe pulmonary disease.
At the initiation of our program we used the standard therapy that had been developed for renal transplantation, namely, azathioprine and steroids. Each of the several immunosuppressive regimens was an improvement as other drugs became available for experimental trial.
Cyclosporine and Fk506, now marketed as tacrolimus seem about equivalent as immunosuppressants. Tacrolimus is a good rescue drug if there are problems with the use of cyclosporine. Both drugs cause an increase in creatinine level. Cyclosporine causes a heavy growth of dark hair on the face and scalp, more unattractive on women than men, hyperplasia of the gums, which can be striking a heaviness of the face, and brutalization of facial features. Tacrolimus causes tremors, sometimes even seizures, and nightmares. Neither is ideal, but our preference at present is for tacrolimus.
In the early 1980s there was a rapid increase in the number of heart transplants performed in the United States. The number in Pittsburgh followed the same course, but then numbers decreased as the number of transplant centers in the United States increased; there are now 150 centers. It is noteworthy that since 1990 the total number of heart transplants has leveled off due to the limited number of donors. Donors are the limiting element in transplantation at present.
There is a pattern of postoperative illness. Acute rejection tends to occur early then peaks again after about 4 to 6 months. Both bacterial and viral infections are problems of the early postoperative period, as is lymphoproliferative disease. Coronary artery disease is a threat throughout, but becomes increasingly more so as the transplanted heart ages.
Patients come at all ages: newborns small children young adults, and 65-year-old seniors. A boy who had a severe cardiomyopathy in 1984 underwent heart transplantation, was quickly reconditioned on the treadmill now is fully employed as a photographer.
There is a down side to transplantation. Some patients have a good immediate result, but over time severe osteoporosis and collapsed vertebrae develop from steroids used in conjunction with azathioprine to control rejection. These problems are not as common in patients taking cyclosporine or tacrolimus, because steroids are used more sparingly. Creatinine level rises almost inexorably with both and tacrolimus cyclosporine administration. Gout is a consequence of steroids, as is osteoporosis and arthritis can require joint replacement—again, from high doses of steroids.
The subsequent failure of the transplanted heart is due to a diffuse obliterative arteriopathy along with acute rejection and resulting fibrosis. This process affects the entire length of the coronary arteries instead of only the proximal branches. There is a similar process in the small bronchi of the transplanted lung. Porter noted it in 1963 among the first kidney transplants. This pathology is characteristic of chronic rejection of heart, lungs, and kidneys; a diffuse allograft vasculopathy.
Almost all of the improvement in survival that we have been able to obtain has been in the early postoperative period. By improved early care and management of infection and rejection, which are the two ogres of transplantation we improved the 1-month survival from 50% to 94% in 1996. However, the slope of the survival rate has remained only slightly better than in the first decade of heart transplantation.
Then, in our younger days when cardiac surgery was developing, a young academic surgeon's research project would be to develop a new operative technique, close a septal defect develop a prosthetic valve, or study hypothermia. Today in Pittsburgh, his research would be in molecular surgery, to manipulate cytokines, genes, or some of a host of enzymes, many having to do with nitric oxide, small quantities of which can turn on specific cellular functions.
With modern techniques it is possible to identify specific cells and determine their origin, whether from donor or recipient. A large number of patients, many of whom were treated by Starzl over the years, have now been restudied it is clear that in patients who do well, not only do cells of the recipient, and host enter the donor organ, but also cells of the donor organ enter the recipient. Donor cells can be found in bone marrow, lymph nodes, heart, and intestines—throughout the body. This is more common with liver cells, but the same thing happens with transplanted lungs, hearts, and kidneys This is like the Chimera the she-monster of Greek mythology that had a lion's head, a goat's body, and a serpent tail, all living together in one individual.
How donor cells survive and proliferate in the recipient host is under study at Pittsburgh and elsewhere. If cells survive and prosper in the recipient, why can't organs be made to do likewise? Knowledge of microchimerism adds hope to this quest.
It was a very lucky break for me to begin my surgical career, along with Harry Muller, at the dawn of modern cardiovascular surgery. I have not been clinically active with cardiac transplantation for the last decade. I am indebted to many people along the way, and am grateful to other members of our cardiothoracic division for continuing this work.
Acknowledgments
In the preparation of the manuscript, I owe a special debt of gratitude to Drs Bartley P. Griffith and Si M. Pham.
Footnotes
Presented at Cardiovascular Surgery—Then and Now, University of Virginia Medical Center, Charlottesville, VA, April 26, 1997.
Address reprint requests to Dr Bahnson, University of Pittsburgh, 1084 Scaife Hall, Pittsburgh, PA 15261.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
