SERUM HYALURONATE IN THE ASSESSMENT OF LIVER ENDOTHELIAL-CELL FUNCTION AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN THE RAT

This study was designed to evaluate the use of serum hyaluronate as a marker of liver endothelial cell function after liver transplantation. We performed orthotopic liver transplantation in both isogeneic and a llogeneic rejector models. After transplantation, hepatocyte function was assessed on the basis of serum ALT and total bilirubin levels, and liver endothelial cell function was judged on the basis of serum hyal uronate levels. Significant increase of hyaluronate in the rejector mo del, compared with the isogeneic model, was seen before any significan t results could be obtained from conventional liver function tests. Th e impaired metabolism of hyaluronate in the rejector model was observe d after intravenous injection of trace amounts of radioactive material . Serial studies demonstrate that the endothelial cell is a more susce ptible target for the immune response than the hepatocyte. Serum hyalu ronate concentration may be a better indicator in the early assessment of graft function. We also examined serum hyaluronate levels to evalu ate cold ischemia-reperfusion injury to the liver endothelial cells in the isogeneic model. At 2 hr after reperfusion, hyaluronate levels in the 6-hr cold ischemia (nonviable allograft) group were significantly higher than in the 1-hr and 3-hr cold ischemia (viable allograft) gro ups. However, there was little difference between the viable allograft groups. After an intravenous injection of 1 mg/kg hyaluronate, the hy aluronate elimination rate in the 3-hr group was distinctly slower tha n that in the 1-hr group. These data indicate that the hyaluronate eli mination rate may be a more sensitive marker of liver endothelial cell function in viable liver after a short period of ischemia.