THE USE OF COMBINED PRESERVATION TECHNIQUES FOR EXTENDED STORAGE OF ORTHOTOPIC LIVER HOMOGRAFTS.

Abstract

During the 12 years since homotransplantation of the whole canine liver was first described by Welch, there have been reports of several techniques of hepatic homograft preservation in dogs. Goodrich and his colleagues showed that livers removed at normal temperatures became unsuitable for transplantation within 20 or 30 minutes. The first protective device used in our laboratories (15) and by Moore and his associates was hypothermia, induced first by whole body cooling of the donor to 30 degrees C. and then perfusing the excised liver with a chilled electrolyte solution. With a fall in the hepatic core temperature to approximately 15 degrees C., these organs could support the life of recipient dogs if revascularized as orthotopic homografts within 2 hours. After longer times, there was a high rate of acute failure due to outflow block of the transplants, a hemorrhagic diathesis, and acute liver failure. Almost identical conclusions about the efficacy of this simple approach were reached by Ono and his co-workers in experiments which did not involve homotransplantation. Subsequent efforts to extend the acceptable storage time have been disappointing. In dogs, Marchioro and his associates reported a method of hypothermic cadaveric perfusion with the use of an extracorporeal heart-lung apparatus into which a heat exchanger was incorporated. Either the entire corpse or the lower half of the dog was perfused. Orthotopic homotransplantation was performed with livers removed from 2 to 8 hours after the sacrifice of the donors. Eight of the 10 recipients which were treated with azathioprine survived operation, but all died within 1 to 5 days thereafter. Mikaeloff and Kestens and their associates used a similar principle in which hypothermic perfusion in situ was limited to the liver. They were able to obtain long term recipient survival after homotransplantation of canine livers removed as long as 6 hours after death. Their technique was an application of a method described several years earlier by Kestens and McDermott. More complex methods have been tried. Brown and his colleagues have evaluated a combination of freezing to − 6 degrees C., immersion into a dimethylsulfoxide or glycerol bath, and dehydration. After 1 to 5 days, the organs were viable but severely damaged and apparently incapable of supporting life as orthotopic homografts. When Moss and his co-workers cooled livers to −20 to −60 degrees C. for 1 to 14 days without dehydration, there was almost no function after the homografts were transplanted to the pelvis. Furthermore, all of the recipients died in 6 hours or less. Recently, there have been 2 reports of conservation of hepatic homografts for 8 to 24 hours, a combination of perfusion, hypothermia, and hyperbaric oxygenation being used. Slapak and his associates placed puppy livers preserved in this way in the neck of adult recipients and found that bile was produced in 8 of 19 experiments. Their perfusing fluid did not contain red blood cells. In a preliminary report from our laboratory (3), chronic survival was described of adult canine recipients that received orthotopic hepatic homografts which had been preserved for almost a day after sacrifice of the donor. In these experiments, the perfusate contained diluted blood. As will be documented, further experience has shown that a significant rate of survival can be attained with such conserved organs if attention is paid to several important details.