Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate.
OBJECTIVE
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 during preservation could improve the energy state and metabolism of cold-stored rat liver.


METHODS
In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were 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 evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups (n=6 in each group).


RESULTS
In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/-106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2: 500+/-29 microl/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 decrease in protein degradation may be related to the modification of cell volume.
Neveux
N
N
Laboratoire de Biochimie A, Hôpital de l'Hôtel Dieu, AP-HP, Paris, France.
De Bandt
J P
JP
Fattal
E
E
Hannoun
L
L
Poupon
R
R
Chaumeil
J C
JC
Delattre
J
J
Cynober
L A
LA
D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D015925:Cryopreservation; D004337:Drug Carriers; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014022:Tissue Survival; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D004337:Drug Carriers; D008081:Liposomes; D000255:Adenosine Triphosphate; D010447:Peptide Hydrolases