EFFECT OF GLYCINE IN DOG AND RAT-LIVER TRANSPLANTATION

Glycine has been shown to protect renal tubule cells and hepatocytes f rom ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusi on injury by infusion into recipients of liver transplantation. In thi s study, the effects of glycine on survival and postoperative liver in jury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solutio n were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of pre servation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glyci ne group). In the dog, omission of glutathione from the UW solution re sulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW sol ution for 24 or 48 hr, there was a decrease in the degree of hepatocel lular injury. After 48 hr of preservation, peak aspartate aminotransfe rase, alanine aminotransferase, and LDH were reduced by about 45-55% w hen glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statis tical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups th at received livers preserved with the UW solution plus or minus glycin e infusion. Hepatamine, a parenteral nutrition solution containing gly cine and other amino acids increased hepatocellular injury (higher con centrations of aspartate aminotransferase, alanine transferase, and LD H versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to r ecipients of livers preserved for 24 or 48 hr and suppresses hepatocel lular injury, as reflected in a reduction in the concentration of seru m enzymes. However, the differences, with and without glycine, were, a t best, marginal and further studies are needed to determine whether g lycine would make a significant improvement in liver preservation and prevent primary nonfunction.