ASSESSMENT OF DAMAGE AND RECOVERY OF SINUSOIDAL ENDOTHELIAL-CELL FUNCTION BY IN-VIVO HYALURONIC-ACID UPTAKE IN COLD-PRESERVED AND TRANSPLANTED RAT LIVERS

We sought to evaluate the significance of endogenous hyaluronic acid l evels and in vivo uptake of exogenous hyaluronic acid as markers of li ver endothelial cell damage and correlate these findings to graft surv ival/function in a rat orthotopic liver transplant model, Endogenous h yaluronic acid levels were measured after orthotopic liver transplanta tion performed with freshly explanted livers, with livers preserved fo r 30 hr, and after sham operation, Exogenous hyaluronic acid uptake wa s evaluated in six study groups: fresh liver grafts, livers preserved for 12 hr, 24 hr, 30 hr and 48 hr, and sham-operated livers, Endogenou s hyaluronic acid levels fell after orthotopic liver transplantation w ith freshly harvested livers and after sham operation, but rose in ani mals transplanted with livers preserved for 30 hr (P<0.01 vs, sham ope ration), In the preserved group, there was no difference in endogenous hyaluronic acid levels between survivors and nonsurvivors. Uptake of exogenous hyaluronic acid was significantly lower after orthotopic liv er transplant with grafts preserved for 12 hr than after sham operatio n or orthotopic liver transplant with nonpreserved livers (P<0.05). Hy aluronic acid uptake further deteriorated in the 24-, 30-, and 48-hr g roups, No significant difference in hyaluronic acid elimination rate w as found when results obtained from livers preserved for extended peri ods (>12 hr) were compared in survivors and nonsurvivors, Hyaluronic a cid uptake was reevaluated in surviving animals after 2 weeks, Complet ely restored function was observed in all survivors, indicating recove ry of endothelial cells, We conclude that endogenous hyaluronic acid l evels and exogenous hyaluronic acid uptake are reliable markers of liv er sinusoidal endothelial cell function and that normal or moderately compromised hyaluronic acid uptake is associated with good graft funct ion, On the other hand, endothelial cell dysfunction suggested by poor hyaluronic acid elimination is not a completely reliable predictor of subsequent deterioration of graft function in rat liver transplantati on.