A study of the metabolites of ischemia-reperfusion injury and selected amino acids in the liver using microdialysis during transplantation

Background. Preservation and ischemia-reperfusion injury still impact the outcome of orthotopic liver transplantation. The authors used microdialysis with a view to monitoring its effect on graft function. Methods. A microdialysis catheter was inserted into the graft immediately after reperfusion and perfused with an isotonic solution for 48 hr. Metabolites of the ischemia-reperfusion injury and selected amino acids were studied. There were 18 patients, with a median age of 52 years (range, 38 - 62 years), 8 of whom were men. Lactate, pyruvate, glycerol, and glucose levels were measured. In addition, alanine, arginine, citrulline, gamma-aminobutyric acid (GABA), glutamate, glutamine, glycine, and taurine were determined. Results. All grafts functioned well. High lactate, pyruvate, and glycerol levels were observed in the immediate postoperative period. These showed a significant rapid decrease and stabilized to baseline levels. Alanine, glutamate, GABA, and taurine levels declined significantly to baseline values. Arginine levels were low immediately postreperfusion and then increased, reaching significantly higher values beyond 19 hr. Conclusions. These data may represent "normal" changes seen in the immediate posttransplant period because all grafts functioned well. Two important metabolic fates of arginine in the liver are in the detoxification of ammonia by means of the urea cycle, and in the synthesis of nitric oxide (NO). Low extracellular arginine may reflect influx of the amino acid into hepatocytes, resulting in formation of NO in the presence of inducible NO synthase or conversion to ornithine in the presence of arginase in the urea cycle. As the organ stabilizes, restriction of arginine uptake may give rise to the observed increase in extracellular arginine.