Folkert O. Belzer, M.D.

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ORGAN PRESERVATION: A PERSONAL PERSPECTIVE
Folkert 0. Belzer

Early Experience in Kidney Transplantation

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My interest and involvement in organ transplantation and preservation started in San Francisco in 1966. I had been working in England in 1965, and when I returned to San Francisco, Dr. J. Englebert Dunphy, the Chairman of the Department of Surgery at the University of California, San Francisco, suggested that I work with John Najarian, M.D. Najarian had started a kidney transplant program about two years earlier and in that time, had performed approximately 40 kidney transplants in San Francisco, all from living-related donors. My task was to develop a cadaver kidney transplant program to supplement that program. At that time, the first heart transplant had not yet been performed, and brain death had not been clinically accepted by eilher the medical profession or the public.

Cadaver kidneys were typically removed after cardiac arrest and, therefore, always experienced a period of warm ischemia. Littie was known about how warm (or even cold) ischemia affected the viability of the human kidney. It was known, however, that the longer the blood supply was severed from an organ, the greater was the likelihood of organ injury and loss of viability. Thus, we attempted, as much as possible, to limit the time between removal of the cadaveric kidney and its transplantation. The first few cadaveric kidney transplants performed by John Najarian and me were done by a method similar to that used for hepatic transplantation prior to 1987. I would start the donor operation after cardiac arrest and remove one kidney. If this kidney appeared to be transplantable, a call was made to Najarian at Moffitt Hospital, and he would start the recipient operation. The kidney would be rushed from the donor hospital - usually in San Francisco - to the University Hospital, where it would be transplanted immediately, limiting the ischemic time as much as possible.

Although the effects of these kidney transplants were dramatic and cadavers could be used as a source for organs, it was obvious that a better method of kidney transplantation was necessary. Specifically, we needed an improved method of preserving the organs so that higher quality kidneys could be obtained and there would not be such an emergency created by the procedure. Thus, I turned my attention to the laboratory to work on this problem.

Beginning Kidney Preservation

I had been in the laboratory with Bob Hoffmann and Glenn Downes, studying hepatic blood flow. The urgent need for an effective method to preserve the kidney forced us to abandon our studies and switch to studying hypothermic perfusion of the kidney. In a previous study, I had shown that continuous perfusion with whole blood was possible only for a short period of time and resulted in an increase in perfusion pressure within one-half hour of perfusion (1). Thus, we switched our attention to the use of plasma as a perfusate. With plasma, the perfusion pressure rise was delayed, but still occurred after about six to 10 hours, and no kidney was viable in the dog after 24 hours of perfusion. By incorporating a membrane oxygenator into the perfusion system and using a pulsatile pump, the rising perfusion pressure could be delayed further, but consistent viability was never obtained.
 Although the success generated in any experimental laboratory depends upon inspiration and perspiration, it also helps to have some luck. We had always collected plasma from donor dogs and kept it frozen. The frozen plasma was taken from the freezer and allowed to thaw out overnight prior to the experiment. One morning, I arrived at the laboratory and found that the plasma had not been removed from the freezer the night before. Rather than postpone the experiment, we thawed the plasma rather rapidly by running it under hot water. To our surprise, the plasma was very turbid, quite unlike that we had previously used which had been thawed slowly. To obtain a clear solution, we filtered the plasma. The dog kidneys perfused with this plasma did not show a rise in perfusion pressure, and the kidneys functioned well afler 24 hours of preservation and autotransplantation.

Subsequent studies showed that freezing and rapid thawing had produced coalescence of unstable lipoproteins in the plasma, which were then removed by the filtration (2). In the earlier experiments, these microaggregates of unstable lipoproteins had become trapped in the kidney's capillary system, especially in the glomerulus, and produced the rising perfusion pressure. This factor in unsuccessful hypothermic perfusion preservation of the kidney had now been eliminated. We named the new solution "cryoprecipitated plasma (CPP)" and used it to preserve dog kidneys for up to 72 hours with 100 percent survival afler autotransplantation (3). This method of preservation was now ready to be tested in the clinical situation.

In August 1967, a middle-aged man with amyloidosis presented with renal failure, but because of his systemic disease, he had not been considered suitable for dialysis or for kidney transplantation. I had just harvested a kidney, which was placed on the preservation circuit in the laboratory (Figs. 1,2). I worked alone in San Francisco
at this time; Najarian had leR for Minnesota, and Dr. Sam Kountz would not arrive until several months later. I discussed the option to accept this kidney with the patient; he accepted. The transplant was performed with a total preservation time of 17 hours. The kidney (Fig. 3) functioned immediately, although not perfectly, and hypothermic perfusion preservation of a human kidney had become a reality (4). We were still unsure of human kidney tolerance to hypothermic preservation and, consequently, wanted to begin perfusion preservation immediately afler harvesting the kidney in the donor hospital. However, we did not have a machine that was sufficiently portable to carry to the donor hospital. An unanended laundry cart was found in the hospital corridor one night and was immediately requisitioned for use in our laboratory. With the expertise of Chester Truman from the instrument shop at Moffin Hospital, the laboratory perfusion equipment was modified to fit onto this cart. It was a wonderful machine to behold because everything moved. The membrane oxygenator, one of the first built by the Waters Company, consisted of a silastic envelope in which the fluid was oxygenated. This moved with a rocking motion. The pulsatile pump, organ chamber, and arterial and venous reservoirs were all made in the laboratory but functioned surprisingly well. It took two or three people to move the machine, and with a rented Avis truck and a forklift we were able to travel to any hospital in the vicinity (Fig. 4).

The first few times we used this perfusion machine, one of our procurement technicians, Ken Steeper, would drive the truck, while Bob Hoffmann and I sat in the back, supporting and steadying the perfusion machine with our feet. Subsequently, we decided to secure the machine with ropes tied to the truck, which was a fortunate idea. On one of the trips we had to stop suddenly to avoid an accident. The ropes held the machine, but the force of the
stop caused the steel frame of the perfusion cart to bend. Had this happened on one of our previous runs, Bob and I would undoubtedly have been crushed by the machine!

The first human kidney preserved by pulsatile perfusion worked after transplantation, but subsequent transplants were not as successful. Postoperative function in more than half of the first 30 kidneys preserved by pulsatile perfusion was poor or resulted in a nonfunctioning grafl (5). These kidneys, unlike living-related kidney transplants, were obtained from less-thanideal donors (de, nonheart-beating cadavers). We noticed that these kidneys had very low flow rates during hypothermic perfusion. To study this problem we returned to the laboratory and reproduced the clinical situation of the agonal period, including warm ischemia, in the dog. The dog model was inconclusive, but we demonstrated the development of severe agonal vasospasm in the pig kidney preservation model, not only in the renal artery but also in the intrarenal vessels.

We found that this agonal vasospasm could be eliminated by performing a bilateral adrenalectomy one week prior to the donor operation. Thus, the cause of this problem appeared related to the release of catecholamines during the agonal period. We also found that pretreatment of the donor with adrenergic blocking agents such as regitine or dibenzyline (a bener agent because it is long acting) completely abolished the agonal vasospasm (5,6). Pretreatment of all donors with dibenzyline was now introduced into our clinical procurement program resulting in dramatic improvement in the immediate function of the transplanted kidney. Cadaveric kidney transplantation ceased to be an emergency procedure at our hospital, where all cadaveric kidney transplants were performed electively during daytime hours (7)

Other improvements that contributed to simplifying organ harvesting occurred during this same period. The first commercial preservation unit was manufactured by American Hospital Supply. The Avis truck used to transport the machine was upgraded to a custom built van donated to the transplant service by our patients. It was a marked improvement and facilitated transport of this large machine (Fig. 5) with a lift bed to raise the machine in and out of the van and an electric generator to provide electricity. Bob Hoffmann, Ken Steeper, Sam Kountz, Dr. Oscar Salvatierra, and I traveled over 30,000 miles procuring kidneys. There was one nuisance. We were prone to receiving parking tickets whenever we parked the van near the emergency room of the donor hospitals because it looked like a laundry truck. I do not remember which one of us had the brilliant idea to add a red emergency light to the top of the van. We never used the light, and I do not believe that it even worked, but it provided us with a universal parking permit for any location.

Although the preservation machine was large, it was amazingly reliable and was used clinically until 1974. The preservation machine was miniaturized with the help of Chester Truman to obtain a truly portable unit (Fig. 6). This mini-preservation machine was tested extensively in the laboratory and was ready for a clinical trial; the opportunity arose over Christmas in 1971. We had harvested two type-A kidneys, but only one had a suitable recipient at that time. I called my good friend, Hans Dicke, a transplant surgeon in Leiden, The Netherlands, and found that they had a suitable recipient for the remaining kidney. I took the next flight from San Francisco to New York and transferred to the night flight to Amsterdam. I obtained a first class ticket to be sure to have sufficient room for the portable machine. It was Christmas Eve and the first class compartment in the 747 jet was empty except for one other passenger. Thus, I had the undivided anention of five stewardesses who kept bringing ice to keep the kidney cold. I vividly remember the Captain coming down to view the kidney and the preservation unit. He remarked how amazingly science had progressed. Here we were, flying at 30,000 feet at over 600 miles per hour in a remarkable and complex airplane, and here was a iinle homemade plastic box carrying, indeed, a very precious cargo. Afler 37 hours of preservation the kidney was successfully transplanted in a 42-year-old truck driver with polycystic kidney disease (Fig. 7). This was 'Leiden's 84th kidney transplant, and the transplant team included Drs. Dicke, Johan Terpstra, Maurits Kalff and Leo van de Putte. The recipient apparently returned to a normal lifestyle with excellent kidney function until he died 17 years later from a ruptured Berry aneurysm. The portable machine was subsequently produced commercially by Edwards Laboratory in California for several years as the Mini-Beizer unit (Fig. 8) and with some simplification is still used today for clinical kidney preservation at the University of Wisconsin.

A seminal paper was published in 1969 by Geoffrey Collins, M.D., working in Dr. Paul Terasaki's laboratory (8). In this study, dog kidneys were successfully preserved for 30 hours by simple cold storage afler vascular flushout with a solution containing a high concentration of potassium and glucose. These kidneys regained immediate function following autotransplantation. Because of the simplicity of this method, it was rapidly adopted by many clinical transplant centers throughout the world. For the next two decades, very lime was added to clinical preservation. Most studies that appeared during that period anempted to credit or discredit both preservation methods.

During this same time the concept of tissue typing emerged as important in kidney transplantation; some believed in this concept, while others did not. Thus, this controversy was further fueled by the fact that simple cold storage would allow easier sharing of kidneys between transplant centers on the basis of tissue typing. Because sharing of kidneys was simpler by cold storage than by continuous perfusion, cold storage became a more popular method. Actually, one of the reasons that our group developed long storage periods for the kidney was to allow sufficient time for tissue matching and sharing of the organ. Sam Kountz was a strong believer in the value of tissue typing for matching kidneys with recipients. I had become disillusioned with the value of tissue typing because in our own, rather large series of cadaver kidney transplants we could not show a beneficial effect of tissue typing for long-term grafl survival (9). However, our interest in preservation by perfusion continued because immediate function of the kidney afler transplantation was bener with this method of preservation than with simple cold storage (10). We continue to use this method clinically for kidney preservation.

In the late 1960s and early 1970s, we attempted to use the same method of preservation developed for the kidney for two other organs - liver and heart. Our interest in liver preservation was stimulated by three clinical liver transplants performed by Dr. Alfred DeLormer and me in the early 1970s. While working in our laboratory, Dr. Donald Trunkey did a large number of experiments with dog heart transplants, none of which was successful. Dr. Robert May, Bob Hoffmann, and I did more than 120 porcine liver transplants without achieving consistently successful survival after 24-hour preservation (11). Because clinical liver transplant results were also quite dismal at that time, we decided to abandon further attempts to preserve the liver or heart.

Successful perfusion preservation of the kidney stimulated another area of clinical interest for me. In 1968, two young women were admired to the University of California at San Francisco Hospital because of severe hypertension secondary to bilateral fibromuscular dysplasia of the renal arteries extending into the branch arteries.
 This condition was considered inoperable at that time, and both patients underwent unilateral nephrectomy of the more severely involved kidney with subsequent discharge from the hospital, still hypertensive and with only half of their renal reserve.

Once again we took this problem to the experimental laboratory and in dog kidneys, showed that the branch vessels could be reconstructed using ex vivo hypothermic perfusion and microvascular repair (12). In February 1972, a 38-year-old woman was admired to University Hospital with uncontrollable hypertension secondary to advanced bilateral fibromuscular dysplasia of both renal arteries with extension into the branch arteries. We operated on her in two stages, undertaking left nephrectomy ex vivo, renal artery repair, and autotransplantation with subsequent similar repair on the right side. Afler her surgery she become normotensive with normal renal function (13). The first autotransplant of the kidney had been performed in 1962 by Dr. Hardy for a ureteral injury (14), and the first autotransplant for renal artery disease was performed by Woodruff in 1965 (14,15); credit for the first ex vivo repair of the renal artery for renal vascular hypertension should go to Dr. Ota and his colleagues (16). This young woman, however, was the first patient in North America to be treated successfully by this combined method. We subsequently performed a larger clinical series of ex vivo renal repairs, again with good results (17). Although fibromuscular dysplasia can now usually be successfully treated by balloon dilatation, an occasional patient will still benefit from this surgical technique.

Move to Wisconsin

I moved to Madison in 1974, having accepted the Chairmanship of the Department of Surgery at the University of Wisconsin. In so doing, l made two excellent decisions and two mistakes. The two excellent decisions were to persuade Bob Hoffmann to join me in Wisconsin and to recruit James Southard, Ph.D., to work in my laboratory. The two mistakes were to forget to ask what my salary was and to find out the location of my laboratory space. The laboratory allocated to me was very small and poorly designed, but it had the advantage of being located across from the only large animal operating room (Fig. 9). Despite the inadequate space, our laboratory became quite productive. I mention this only to remind junior investigators in surgery that, very oflen, the amount of laboratory space is not directly related to one's productivity.

In 1974, the clinical requirements for successful kidney preservation were relatively well met by either simple cold storage or continuous machine perfusion. We had not yet developed an interest in liver, pancreas, or heart preservation because the clinical transplantation of these organs was still very difficult and long-term success rates were not very good. Thus, we turned our research attention to understanding problems in organ preservation, specifically related to basic mechanisms of hypothermic-induced cellular injury and methods to prevent the injury.

Research is oflen based on serendipity, rather than solely on a detailed systematic mechanistic approach to a problem. There is nothing wrong with serendipity, and it oflen leads to successes. For instance, both advances in organ preservation-continuous perfusion and simple cold storagehad an element of serendipity. The development of cryoprecipitated plasma was aided by serendipity. Furthermore, Collins' discovery of an appropriate cold storage solution had a serendipitous element. Collins attempted to mimic the intracellular environment of the kidney and designed a high-potassium solution based on a report by Keeler (18). He ended up with a solution of only 170 mOsm/l, which was hypotonic to the kidney cells. He made the solution isotonic by the addition of a large concentration of glucose (about 130 mM); the addition of this impermeant was one of the main reasons for the success of this solution. Our laboratory was one of the first to show that the effectiveness of Collins' solution was due to the high concentration of glucose, rather than the cations or anions (19). Thus, potassium and sodium could be interchanged without losing the beneficial effects on the kidney,as long as either glucose or sucrose were added to the solution.

Although serendipity continues to be an important aspect of our research in organ preservation, there is no doubt that a more systematic approach could also lead to improving organ preservation. Thus, we began a more deliberate and basic consideration of how to develop improved organ preservation methods. Our goal was then, as now, to obtain truly long-term kidney preservation - weeks to months, rather than hours or days. To achieve truly longterm preservation may require cryopreservation (freezing) of the organ, an area in which we were not interested. Another possibility, however, is continuous perfusion, and we continued to experiment with this method of organ preservation. We continued to focus on the canine kidney and expanded to use models other than transplantation, including tissue slices, cell homogenates, isolated mitochondria, isolated perfused organs, and isolated cellular preparations.

The laboratory worked very hard, but results were slow to develop. Initially, we realized that endothelial cell injury appeared to limit long-term kidney preservation, and every kidney transplanted afler five-day preservation turned black on reperfusion, signaling organ failure. We felt that this could be due to the unsatisfactory nature of the colloid necessary for oncotic support during continuous perfusion. Serum albumin was the commonly used colloid, but many laboratories had reported that different batches of albumin were bener than others; this suggested that some factor related to albumin may have been causing endothelial injury. To test this, we used a common kitchen blender to whip the perfusate for a short time to accentuate its exposure to air. Afler only 24-hour preservation with this perfusate, the kidney was injured and most kidneys turned black on reperfusion. This simple experiment demonstrated to us that denaturation of albumin could lead to the formation of elements toxic to the endothelium of the kidney. Thus, we began a search for a stable, nontoxic, oncotic agent. We tried many compounds, including gums, dextrans, cross-linked hemoglobin, and albumin, all without success. Finally we found a compound, hydroxyethyl starch (American Critical Care, now DuPont Pharmaceuticals), that gave excellent three-day kidney preservation. The kidneys, however, still turned dark on reperfusion afler five days of preservation. The starch was then subjected to an ultrafiltration-dialysis procedure to reduce the concentration of low molecular weight components (below 50 kilo daltons); this purified starch allowed preservation of the kidney for up to seven days without signs of endothelial injury, and all kidneys remained red on reperfusion although they did not function.

Next we turned our attention to the development of a purely synthetic perfusate for the kidney to take advantage of the beneficial properties of starch as a colloid. Previous albumin-containing perfusates were made in a sodium chloride-based solution, plasma, or Ringer's lactate. We were aware for many years that cells became edematous when stored in the cold, and we looked at the suppression of hypothermic-induced cell swelling. We knew what type of compound was desired - a larger molecular weight anion - but did not know which ones would be nontoxic, readily available, and inexpensive. We scanned the Merck Index looking for agents that would be effective in preventing cell swelling and searched the Sigma catalog to determine if these were available and relatively inexpensive. We found two compounds, gluconic acid and lactobionic acid - both acid forms of saccharides, glucose, and lactose.

It was in 1979 that we finally formulated what we thought was the ideal perfusate; it contained many agents that had a theoretical rationale for protecting the kidney from injury. This solution was called the 'kitchen sink' perfusate because it contained everything but the kitchen sink (Table 1). This solution contained all the ingredients that eventually became the University of Wisconsin (UW) solution, now used widely for organ preservation. However, the UW solution did not guarantee successful kidney preservation. A modified version containing gluconate was developed for human kidney perfusion preservation in 1984. It provided safe, three-day preservation of the kidney and replaced cryoprecipitated plasma. Thus, we had developed a purely synthetic perfusate for our clinical use (20).
 Development ot UW Solution

Several changes occurred in the early 1980s, both clinically and in research. First, we moved into the new medical center (Clinical Science Center), which provided more and bener laboratory and experimental surgery space. Also, Hans Sollinger, M.D., joined the faculty afler finishing his surgical residency at our institution and soon started a clinical pancreas transplant program. Munci Kalayoglu, M.D., who spent two years with Thomas Starzl, M.D., at the University of Pinsburgh' was recruited in 1984 as a pediatric surgeon as well as head of our liver transplant program. Another major change was the introduction of immunosuppressive agents at our center - cyclosporine in 1983 and OKT3 therapy in 1985. The availability of these two agents made pancreas and liver transplantation feasible.

Liver and pancreas transplantations were performed on an emergency basis, usually at night, and it was obvious again that there was a great need for successful preservation of these organs for longer than 24 hours. The success of perfusion for preservation of the kidney and our past experience with perfusion preservation led our group to initiate studies in the perfusion preservation of these two organs. Anthony D'Alessandro, M.D., worked in our laboratory as part of his resident training and had some impressive successes with 24- and 72-hour preservation of the dog liver as tested by orthotopic transplantation. However, this method was cumbersome and the results were inconsistent. Perfusion of the pancreas was also difficult because of its double arterial supply; this organ quickly became edematous during perfusion. Thus, we felt that the development of a method to successfully preserve these organs was going to be difficult and time consuming.

In 1985, Jan Wahlberg, M.D. from Uppsala, Sweden, joined our laboratory as a research fellow and was given the task of preserving the pancreas. We were aware that islet cell functions in the pancreas were relatively resistant to cold ischemia and that there was no need to preserve exocrine function. Therefore, we began to investigate simple cold storage. The first solution tested was similar to the 'kitchen sink'perfusate minus the additives that supported aerobic metabolism. To our amazement, this simplified solution, subsequently called the UW solution, was quite effective and provided consistent 72-hour preservation of the canine pancreas. These results were presented at the American Society of Transplant Surgeons in June 1986 where it auracted lime interest (21). During the same month, three other research fellows joined our laboratory: Neville Jamieson, M.D., from Cambridge, England; Ralf Sundberg, M.D., from Lund, Sweden; and Rutger Ploeg, M.D., from Leiden, The Netherlands. Ploeg showed that the solution used by Wahlberg was effective for three-day preservation of the canine kidney by simple cold storage, but produced inferior renal function when compared to continuous perfusion (22).

Jamieson and Sundberg took over the liver preservation project and initially continued perfusion preservation as begun by D'Alessandro. However, because of the complexities of this method and the fact that relatively short-term preservation of the liver was required for clinical applicability (about 24 to 30 hours), it was felt that simple cold storage might be the method that would satisfy our goals most rapidly. Again, using the same solution as used by Wahlberg, our laboratory showed that livers could be preserved for 24 and 48 hours as tested in the orthotopic liver allografl model (23,24).

These were most encouraging results, and the next step was to introduce this solution into clinical liver and pancreas preservation. Clinical pancreas preservation with the UW solution was begun in 1987. Initially, pancreases were preserved for only short periods, but gradually the length of preservation was extended to up to 30 hours with excellent results. In the summer of 1987, we used the UW solution for clinical liver preservation. We still kept the preservation time under six hours, and the operations were still performed as emergency surgery. Because the transplantation of a poorly preserved liver could be a lifethreatening situation for the recipient, we were very cautious about extending the preservation time.

However, an interesting and unpredictable situation presented itself that summer. We had procured a pediatric liver for a child with biliary atresia, but while the procurement team was harvesting the liver, the child was admitted for emergency surgery and found to be HIV positive. His distraught parents took the child home. Subsequently, the child was found to be HIV negative and was successfully transplanted several weeks later. We attempted to send the unused liver to another institution, but there was a concern that the preservation time was too long. The liver was in the cooler in the UW solution, and I thought that this would be a good opportunity to test the effects of a long-term preservation of the liver by performing a xenotransplant into a baboon. The next morning an adult baboon was obtained from another investigator at the University, and a successful xenograft was performed after 20 hours' preservation of the liver. The baboon's liver functions were near normal the day following surgery, but, unfortunately, the animal died 36 hours postsurgery from an anaphylactic reaction against infused human platelets. This experiment showed that the human liver was tolerant to up to 20 hours' cold storage in the UW solution and gave us confidence that we could extend our current clinical limit of about six hours to longer times.

Soon afler this episode, a patient with end-stage liver disease was transferred from the intensive care unit of one of our referring hospitals to our intensive care unit. A liver became available in Texas, and because the recipient required a number of diagnostic procedures, the transplant was scheduled for 8:00 AM the next morning. The liver was successfully transplanted after 20 hours of preservation (Fig. 10); the recipient was extubated the next day and transferred to the transplant unit on the second postoperative day with excellent liver functions. He is alive and well today. Elective and scheduled liver transplantation became a reality and we continue to perform this operation on a scheduled basis unless the recipient's condition requires an emergency liver transplantation (25). It is interesting that this first elective liver transplant occurred exactly 20 years afler the first successful elective kidney transplant.

The results of liver and pancreas preservation with the UW solution were first presented at the International Transplant Congress in Pinsburgh honoring Tom Starzl for his pioneering work in organ transplantation. We presented our experimental results along with some of the clinical results, and the aRendees at the Congress seemed to be impressed. I think the anention was greatest, however, when I presented two slides: one showing Starzl sleeping in a Lear jet and the other showing me sleeping at home in my own bed. These slides illustrated the benefits, at least to the surgeon, of having an available method for preserving the liver for 24 hours or more. No longer would it be necessary for all livers to be harvested and immediately transplanted, regardless of the hour.

Our experience with the UW solution in clinical liver and pancreas transplantation was soon tested at other centers and its efficacy confirmed. Although the UW solution has received most of its anention from liver preservation, its effect on pancreas preservation and transplantation is, in my opinion, just as significant. At our center, it has almost completely eliminated vascular thrombosis, postoperative grafl pancreatitis, and primary nonfunction (26).

Our preservation laboratory continues to work on the basic mechanisms of organ injury during hypothermic storage. One of our next goals is successful preservation of the heart. Long-term organ storage remains nearly as elusive as it was 20 years ago, but we have made some progress in clinical organ preservation for transplantation of the intraabdominal organs. In the future, we hope to have similar success in the preservation of intrathoracic organs.

Experimental organ preservation in the laboratory and the clinical application of our results has been an important and very gratifying part of my academic and professional life over the past 25 years. I am especially grateful to my colleagues, Jim Southard, Bob Hoffmann, the late Glenn Downes, and the many technicians, residents, and research fellows who contributed enormously to our modest successes. Table 2 lists the surgeons from overseas who contributed to our efforts and were a major force in what has been accomplished. My transplant colleagues, Hans Sollinger, Munci Kalayoglu, John Pirsch, and Tony D'Alessandro, as well as our transplant fellows, have been enthusiastic and major contributors to our results. I am also very grateful to the National Institutes of Health for their uninterrupted support for the past 25 years.
 Preservation is only a small part of the overall picture in transplantation. Many hands, heads, and hearts are necessary for such successful undertakings. I have been fortunate to have been joined by many fine professionals. Without the excellent skills of a highly competent and dedicated staff of transplant surgeons, physicians, organ procurement personnel, nurses, and others, it would have been much more difficult to show how organ preservation is effective in the clinical situation. When l look back over the past years, I must admit that, as a clinician, my satisfaction has come from surgery and the care of the surgical patient. As an academician, my satisfaction has come from teaching medical students, especially surgical residents and transplant fellows. The laboratory, however, has been the most stimulating to my intellect, both when things went well and when there was little progress. The experimental laboratory provides an opportunity to be creative and to make discoveries that can improve the quality of life for our patients.

REFERENCES

1. Beizer FO, Park HY, Vetto RM. Factors influencing renal blood tlow during isolated perfusion. Surg Forum 1964; 15:222.

2. Beizer FO, Ashby BS, Huang JS, et al. Etiology of rising perfusion pressure in isolated organ perfusion. Ann Surg 1968; 168:382.

3. Beizer FO, Ashby BS, Dunphy JE. 24-hour and 72-hour preservation ot canine kidneys. Lancet 1967; 2:536.

4.Beizer FO, Ashby BS, Gulyassy PF, et al. Successful 17-hour preservation and transplantation of human-cadaver kidney. N Engl J Med 1968; 278:608.

5. Beizer FO, Reed TW, Pryor JP, et al. Cause of renal injury in kidneys obtained from cadaver donors. Surg Gynecol Obstet 1970; 130:467.

6.Keaveny TV, Pryor JP, White C, et al. Renal vasomotor responses in the agonal period. Angiology 1971; 22:77.

7.Beizer FO, Kountz SL. Preservation and transplantation of human cadaver kidneys: A two-year experience. Ann Surg 1970; 172:394.

8.Collins GM, Bravo-Shugarman M, Terasaki Pl. Kidney preservation for transportation. Initial perfusion and 30 hours' ice storage. Lancet 1969; 2:1219.

9.Beizer FO, Perkins HA, Fonmann JL, et al. Is HLA typing of clinical significance in cadaver renal transplantation? Lancet 1974; 1:774.

10.Beizer FO. Preservation of cadaver kidneys: Cold storage or machine perfusion. Arch Surg- Ed 1983.

11.Perkins HA, May RE, Beizer FO. Cause of abnormal bleeding after transplantation of pig liver stored by a perfusion technique. Arch Surg 1970; 101:62.

Beizer FO, Keaveny TV, Reed TW, et al. A new method of renal artery reconstruction. Surgery 1970; 68:619.

13.Beizer FO, Salvatierra O, Perloff D, et al. Surgical correction of advanced fibromuscular dysplasia of the renal arteries. Surgery 1974; 75:31.

14.Hardy JD. High ureteral injury: Management by autotransplantation of the kidney. JAMA 1963; 184:97.

15.Woodruff MFA, Doig A, Donalds KW, et al. Renal autotransplantation. Lancet 1966; 1:433.

16.Ota K, Mori S, Awane Y, et al. Ex situ repair of renal artery for renal vascular hypertension. Arch Surg 1967; 94:270.
 17.Beizer FO, Salvatierra O, Palubinskas MD, et al. Ex vivo renal artery reconstruction. Ann Surg 1975; 182:456.

18.Keeler R, Swinney J, Taylor RMR, et al. Br
J Urol 1966; 38:653.

19.Downes GL, Hoffmann RM, Huang JS, et al. Mechanism of action of washout solutions for kidney preservation. Transplantation 1973; 16:46.

20.HoHmann R`A, Southard ~1H, Lutz M, et a\. 72 hour preservation of dog kidneys using a purely synthetic perfusate containing hydroxyethyl starch. Arch Surg 1983; 118:919.

21.Wahlberg JA, Love R, Landegaard L, et al. 72 hour preservation of the canine pancreas. Transplantation 1987; 43(1):5.

22.Ploag RJ, Goossens D, Vreugdenhil P, et al.
Successful 72 hour cold storage kidney

preservation with UW solution. Transplant Proc 1988; 20:935.

23.Jamieson NJ, Sundberg R, Lindell S, et al. Successful 24-30 hour preservation of the canine liver. Transplant Proc 1988; 20(1):945.

24.Jamieson NV, Sundberg R, Lindell S, et al. Preservation of the canine liver for 24-48 hours using simple cold storage with UW solution. Transplantation 1988; 46(4):517.

25.Kalayoglu M, Sollinger HW, D'Alessandro AM, et al. Successful extended preservation of the liver for clinical transplantation. Lancet 1988; 1:617.

26.Sollinger HW, Stratta RJ, D'Alessandro AM, et al. Experience with simultaneous pancreas-kidney transplantation. Ann Surg 1988; 208(4):475.
 

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