Polyethylene Glycol Modified-Albumin Enhances the Cold Preservation Properties of University of Wisconsin Solution in Rat Liver and a Hepatocyte Cell Line 1 Rime Abbas, M.D.,* Rajan S. Kombu, Ph.D.,† David Dignam, Ph.D.,‡ William Gunning, Ph.D.,§ Jonah J. Stulberg, M.P.H.,* , k Henri Brunengraber, M.D., Ph.D.,* , † and Juan R. Sanabria, M.D., M.Sc.* , † ,2 *Department of Surgery; †Department of Nutrition; k Department of Biostatistics, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; ‡Department of Biochemistry and Molecular Biology; and §Department of Pathology, University of Toledo College of Medicine, Toledo, Ohio Submitted for publication January 5, 2009 Liver grafts preserved in cold storage undergo changes mainly manifested by morphological modifi- cations of the sinusoidal endothelium that result in poor graft function upon reperfusion. The present studies aimed to determine if the addition of polyethyl- ene glycol-albumin to University of Wisconsin (Peg- AlbUW) solution ameliorates the cold preservation injuries of liver grafts. Rat livers were preserved cold with various preservation solutions and evaluated for weight changes and endothelial morphology. Solu- tions that preserved graft weight and endothelial mor- phology were tested in the isolated perfused rat liver model to assess graft function. A rat hepatocyte cell line was evaluated for both viability and glutathione concentrations emulating cold preservation and reperfusion conditions. Liver grafts preserved with Peg-AlbUW maintained their initial weight and showed a conserved endothelial morphology com- pared with liver grafts preserved in UW for 30h (P < 0.05). Liver grafts preserved with Peg-AlbUW had improved portal blood flow and bile secretion com- pared with liver grafts preserved in UW for 30h (P < 0.05). In vitro we noted comparable hepatocyte vi- ability when cells were preserved in Peg-AlbUW versus UW under similar preservation conditions (P > 0.05); glutathione concentrations (reduced and total) were significantly increased in hepatocytes preserved in 3% Peg-AlbUW compared with other preservation solu- tions (P < 0.05). The addition of Peg-Alb to UW preservation solution ameliorated the cold preservation injuries of rat liver grafts as shown by stable liver graft weight, a better preservation of the endothelial morphology, improved portal vein blood flow, and increased bile secretion. Peg-Alb-UW solution improved the integrity of the glu- tathione redox buffer system of a hepatocyte cell line after cold storage and reperfusion. Ó 2010 Elsevier Inc. All rights reserved. Key Words: liver transplant; cold ischemia; reperfu- sion injury; glutathione. INTRODUCTION Liver transplantation is the standard therapy for se- lected patients with end-stage liver disease and acute liver failure. Advances in surgical techniques, in post- transplant immunosuppressive regimens, and organ preservation solutions have allowed for an 87% 1-y sur- vival rate for transplanted patients [1, 2]. Despite 6650 liver transplants performed in the U.S.A. in 2006, a greater treatment demand combined with a paucity of donors still poses the challenge of organ shortage [2]. Liver graft recovery after reperfusion depends on a delicate balance between cold preservation injuries and graft potential for regeneration; technical, immu- nological factors, and the overall reserve of the recipi- ent also play a role [3]. Herein, we focus on injuries the liver graft may sus- tain during the cold preservation period. The sinusoidal endothelium was found most susceptible to cold 1 This work was presented in part at the AHPBA, Miami, 2006, and at the AASLD, Boston, 2007. 2 To whom correspondence and reprint requests should be addressed at University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Division of Transplant and HB Surgery, Department of Surgery, 11100 Euclid Ave Lakeside 7506, Cleveland OH 44106-5047. E-mail: juan.sanabria@uhhospitals.org. 0022-4804/$36.00 Ó 2010 Elsevier Inc. All rights reserved. 95 Journal of Surgical Research 164, 95–104 (2010) doi:10.1016/j.jss.2009.03.030