A comparison of histidine-lactobionate and UW solution in 48-hour dog liver preservation.
Many modifications of the UW solution have been reported to yield successful results in rat liver preservation and transplantation. One solution used histidine, in combination with lactobionate (HL-I), and gave superior preservation of the rat liver when compared with the UW solution. In this study we have compared the HL-I solution with 90 mM histidine, HL-II solution with 30 mM histidine, and the UW solution in dog liver preservation and transplantation. Dog livers were preserved for 48 hr in one of the three solutions and transplanted. The peak AST and ALT values were highest in livers preserved in HL-I, intermediate in UW solution, and lowest in HL-II. However, there were no significant differences among survival rates (average 5-7 days per group), posttransplant serum concentration of liver enzymes (AST, ALT, LDH, and alk-phos), clotting factors (PT and PTT), bilirubin, and fibrinogen concentration for each group. Dogs were sacrificed or died within 5-7 days due to rejection in nonimmunosuppressed dogs. Also, rat livers were preserved in the HL-II solution or in a solution in which histidine was replaced by isoleucine (IL-I). Isoleucine is an amino acid with a molecular mass similar to that of histidine, but is not as good a hydrogen ion buffer as histidine at the pH used for liver preservation (7.4). The buffer capacity of the IL-I solution was similar to the UW solution, but about one-half as much as the HL-II solution. Rats receiving a liver preserved for 30 hr in HL-II or IL-I were 100% viable. Rats receiving a liver preserved for 40-44 hr in HL-II or IL-I showed less survival (33% and 25%, respectively). This shows that histidine can be effectively replaced by isoleucine in a preservation solution and gives equivalent preservation results. Thus, the mechanism of improvement of liver preservation with histidine is not due to its action as a hydrogen ion buffer. These studies show that, although the HL solutions are superior for preservation of the rat liver, they are not superior to the UW solution for preservation of the dog liver. However, as others have shown in the rat liver transplant model, a simplified UW solution (HL-II) appears effective in dog liver preservation. The dog liver transplant model remains a more appropriate model for testing new preservation solutions prior to initiation of clinical trials.
Sumimoto
R
R
Department of Surgery, University of Wisconsin, Madison 53792.
Lindell
S L
SL
Southard
J H
JH
Belzer
F O
FO
D000241:Adenosine; D000410:Alanine Transaminase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D000493:Allopurinol; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005978:Glutathione; D006639:Histidine; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011887:Raffinose; D051381:Rats; D012996:Solutions
C075029:HL-I solution; C075030:HL-II solution; D007328:Insulin; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D006639:Histidine; D000493:Allopurinol; D005340:Fibrinogen; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose