title: Biliary inorganic phosphate as a tool for assessing cold preservation-reperfusion injury: a study in the isolated perfused rat liver model.
abstract: Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. The bile flow has been suggested as an index of ischemic damage, and severely impaired bile flow seems to be predictive of poor survival in experimental studies. Looking for injury markers, biliary inorganic phosphate has the potential of being a useful endogenous marker of diminished hepatobiliary function because this anion is excreted in the bile by a paracellular pathway and it can detect changes in permeability. The goal of this study was to evaluate the effects of cold preservation-reperfusion of the liver on bile flow and bile inorganic phosphate and their relationship with storage-related graft failure. The isolated and perfused rat liver was used to evaluate the injury for ischemia-reperfusion. The intrahepatic resistance, lactate dehydrogenase release, and potassium and biliary inorganic phosphate concentration were used to estimate viability and function of freshly isolated or cold-preserved livers. The intrahepatic resistance and the bile flow were consistent and significantly decreased throughout the perfusion time in relation to the increment in storage. Inorganic phosphate is more concentrated in bile from preserved livers, showing an alteration in paracellular pathway, confirmed by the biliary excretion of horseradish peroxidase. After preservation, concentration and excretion of the paracellular marker were increased during the first peak. The second peak appears earlier in preserved livers (10 minutes) with a different shape but without changes in concentration. In conclusion, inorganic phosphate in bile shows changes in paracellular permeability as occurs in livers after 48 hours of cold preservation.
authors.affiliation: Farmacologia, Departamento de Ciencias Fisiológicas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Luciana L
authors.initials: LL
authors.lastname: Almada
authors.forename: Angel L
authors.initials: AL
authors.lastname: Scandizzi
authors.forename: Edgardo E
authors.initials: EE
authors.lastname: Guibert
authors.forename: Graciela
authors.initials: G
authors.lastname: Furno
authors.forename: Joaquin V
authors.initials: JV
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D015925:Cryopreservation; D006439:Hemodynamics; D006735:Horseradish Peroxidase; D066298:In Vitro Techniques; D008099:Liver / Q000503:physiopathology; D008102:Liver Circulation; D008297:Male; D009926:Organ Preservation / Q000009:adverse effects; D009994:Osmolar Concentration; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000378:metabolism; D013997:Time Factors; D014022:Tissue Survival
chemical_list: D015415:Biomarkers; D010710:Phosphates; D006735:Horseradish Peroxidase