Organ preservation for transplantation: Early breakthroughs

Abstract

Organ preservation is an important element for the continuous improvement of transplantation. Since the early years of preservation science when there were no effective solutions for preservation except the Locke solution, initially suggested by Carrel as a “physiological balanced fluid and to prevent the formation of clots”,1 there have been several important advances intended to improve preservation times. In this editorial, I analyze some of those early improvements that have enabled better transplant results. In the first edition of the book Organ Procurement, Perfusion and Preservation for Transplantation, in 1982, Humphries and Dennis accurately described the historical developments of preservation.2 They began with Carrel and his advanced concepts regarding the possibility of utilizing solutions that would allow the preservation of arteries in a cold Locke solution for a few days and then their reimplantation into another animal. Carrel did not appear to have preserved organs as we do today, but he predicted that “the perfusion of organs seems necessary for preventing the formation of clots,” and from there, he went on to recommend the use of the Locke solution.1 Carrel recognized that his countryman, Julien Jean César Le Gallois (1770–1814), was the first to mention the idea of organ perfusion, specifically referring to the heart, as a way of maintaining organ viability.2 Despite all the superb advances, many challenges remain, namely in preserving organs with previous injury or those from high-risk donors. During the 1960s feverish enthusiasm swept the minds of innovative surgical investigators as to the best means of consistently preserving organs. In 1967 Belzer and his group from San Francisco reached a milestone when defining the cause of increased perfusion pressure by removing fragile plasma lipoproteins from the perfusate before kidney preservation. The resultant product from this innovative process was called cryoprecipitated plasma,6 and the preservation system included hypothermic pulsatile perfusion. Clinical programs began considering this technique with the possibility of obtaining consistent results after perfusion for transplantation. In 1969, another milestone occurred in the transplantation arena when Collins, Bravo-Shugarman, and Terasaki published a work on the use of intracellular crystalloid solutions in kidney preservation.7 A crystalloid solution and the simple techniques of organ washout and hypothermia appealed to the practical sense of many transplant specialists. The transplantation scene now had two acceptable methods for kidney preservation, the Belzer and the Collins techniques. Attention needed to be directed toward the results observed after periods of preservation longer than 24 hours. Many more clinicians working in the laboratory attempted to simplify the previous methods by changing the composition of the intracellular crystalloid solutions and by modifying the plasma preparation for hypothermic perfusion.2 In our own laboratories, while at the University of Minnesota in Najarian's group, we introduced the silica gel fraction of plasma as a preparation that overcame the cumbersome manufacturing and diminished shelf-life of cryoprecipitated plasma.2 After several changes in preservation solutions and perfusion machines were introduced, like the MOX-100 perfusion machine (Waters Instruments, Rochester, MN) developed and encouraged by the University of Minnesota, the organ preservation arena continued to make small but important advances. In 1987, there was a substantial milestone with the development of a new preservation solution by Belzer's group that resulted in successful canine pancreas preservation under hypothermia for 72 hours.8 It was evident that this solution was a more effective and multiorgan solution than others available in the transplant market. This solution was named the University of Wisconsin (UW) solution because the investigators proceeded from this institution. In the next few years, arival solution emerged, the histidine-tryptophan-ketoglutarate (HTK) solution, with a different composition but with results similar to those achieved with the UW solution.9 Potential elements of improvement have been considered, such as modifications in the composition of the two most efficacious and dominating solutions in transplantation today, UW and HTK. In the terrain of perfusion preservation, a new machine for perfusion of kidneys (Organ Recovery Systems, Des Plaines, IL) is a clinical reality, and new advances in machine development are being pursued in the United States and Europe.10 Despite all the superb advances in organ preservation, many challenges remain, namely, improvements in liver, heart, lung, and small bowel preservation, and improvements in preserving organs with previous injury, such as ischemia, non-heart-beating organ donors, or high-risk donors with some evidence of minimal functional impairment. I hope that in the not-too-distant future, organ freezing will gain the attention of the serious preservation researcher. New organ preservation investigators will have to hone in with all their ability on defining the principles associated with preservation and ischemic injury, as well as on understanding the molecular response to organ preservation damage and, of course, on introducing new drugs that will overcome that potential injury.