A preservation solution with polyethylene glycol and calcium: a possible multiorgan liquid.
The addition of polyethylene glycol (PEG) to hepatocyte storage medium is known to decrease lipid peroxidation and swelling and to protect the cell cytoskeleton from cold. We therefore decided to investigate the effect of substituting PEG for hydroxyethyl starch (HES) in an extracellular-like UW solution, with and without Ca++, on rat liver preservation. Isolated perfused rat livers were used to assess graft injury after 24h of cold storage. Four groups of preserved livers ( n=6 for each group) were compared to controls (non preserved livers, n=11). For this purpose, Belzer solution (K+-UW, group 1) was stepwise modified. Group 2 (Na+-UW) was treated with the same liquid, however with inverted concentrations of Na+ and K+. Group 3 was preserved in the first experimental solution (EPS-1) with Ca++ (0.5mM) added to the Na+-UW solution. In the EPS-2 (group 4), PEG-35 (0.03mM) was substituted for HES. The last group, EPS-3 (group 5) was treated with the same compounds as EPS-2, but without Ca++. After 24h of cold storage and 120min normothermic reperfusion, there was no statistical difference in transaminases (ALT and AST) release between the control and the Na+-UW groups. Furthermore, rat livers preserved in Na+-UW solution released less ( P<0.05) ALT and AST and excreted more ( P<0.05) indocyanine green (ICG) than livers preserved in K+-UW solution. The addition of 0.5mM Ca++ to Na+-UW solution (EPS-1) dramatically increased ( P<0.05) parenchymal (ALT, AST) and non parenchymal (creatine kinase-BB) cellular injury. The substitution of PEG (0.03mM) for HES (EPS-2) reduced ( P<0.05) membrane injuries due to Ca++ while bile flow was statistically increased ( P<0.05). Finally, the omission of Ca++ from EPS-2, that is EPS-3, has no statistically significant effect on the studied parameters. PEG effectively protected the rat liver grafts from the onset of hypothermic ischemia-reperfusion and Ca++ damages and thus may be a valuable additive to preservation solutions.
Laboratoire de Physiologie et de l'environnement, Faculté de Pharmacie, Université Claude Bernard Lyon I, France.
Hassen
H
Ben Abdennebi
Jean-Paul
JP
Steghens
Aoumeur
A
Hadj-Aïssa
Alain
A
Barbieux
Silvina
S
Ramella-Virieux
Claude
C
Gharib
Olivier
O
Boillot
D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D002118:Calcium; D003402:Creatine Kinase / Q000032:analysis; D052276:Creatine Kinase, BB Form; D006498:Hepatectomy / Q000379:methods; D007527:Isoenzymes / Q000032:analysis; D008099:Liver; D008111:Liver Function Tests; D008297:Male; D019188:Organ Preservation Solutions; D010477:Perfusion / Q000379:methods; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000379:methods
D007527:Isoenzymes; D019188:Organ Preservation Solutions; D011092:Polyethylene Glycols; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D052276:Creatine Kinase, BB Form; D002118:Calcium