title: Novel strategy to decrease reperfusion injuries and improve function of cold-preserved livers using normothermic ex vivo liver perfusion machine.
abstract: Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the immediate NELP group, procured livers were immediately placed on NELP for 8 hours. In the cold NELP group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in different durations to 38°C and kept on NELP for an additional 4 hours. For comparison purposes, the last 4 hours of NELP runs were considered to be the evaluation phase. Immediate NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, and β-galactosidase and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentrations of hyaluronic acid and β-galactosidase compared to the cold NELP livers. In addition, there was a significant decline in international normalized ratio values, improved bile production, reduced biliary epithelial cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation, a gradual rewarming protocol before NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation, and SEC dysfunction.
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Babak
authors.initials: B
authors.lastname: Banan
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Departments of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO.|Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI.
authors.forename: Rao
authors.initials: R
authors.lastname: Watson
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Jianluo
authors.initials: J
authors.lastname: Jia
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Gundumi A
authors.initials: GA
authors.lastname: Upadhya
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.|Departments of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO.
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Departments of Surgery School of Medicine, Washington University, St. Louis, MO.
authors.forename: William
authors.initials: W
authors.lastname: Chapman
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001777:Blood Coagulation; D050377:Cold Ischemia / Q000009:adverse effects; D005260:Female; D006498:Hepatectomy; D006820:Hyaluronic Acid / Q000378:metabolism; D007728:Kupffer Cells / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D010477:Perfusion / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017694:Rewarming / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D013552:Swine; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D006820:Hyaluronic Acid; D001616:beta-Galactosidase