Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate

Background/Aims: Energy charge and capacity for adenosine triphosphate (ATP ) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP du ring preservation could improve the energy state and metabolism of cold-sto red rat liver. Methods: In the first set of experiments, the uptake of ATP-containing lipo somes and their effects on hepatic viability were determined in isolated pe rfused unstored rat liver, In the second set of experiments, rat livers wer e preserved for 18 h at 4 degrees C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were ev aluated, In each part, data were compared with adequate control, unloaded l iposome-treated, and free ATP-treated groups (n=6 in each group), Results: In non-stored livers, ATP-containing liposomes were taken up by th e liver; they did not alter hepatic viability and induced a decrease in ene rgy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs, Control), Addition of liposomally-entrap ped ATP during cold storage produced a significant attenuation of the decre ase in hepatic ATP content (Lip ATP 2: 524+/-45 vs, Control 2: 364+/-106 nm ol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis a ssociated with an increase in cell volume compared with the other groups (L ip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Fr ee ATP 2: 500+/-29 mu l/g; p<0.01). Conclusions: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function, The de crease in protein degradation may be related to the modification of cell vo lume.