title: Histological changes during extracorporeal perfusions of the porcine liver: implications for temporary support during acute liver failures.
abstract: Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK. ggravante@hotmail.com
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Gravante
authors.forename: Seok Ling
authors.initials: SL
authors.lastname: Ong
authors.forename: Angus
authors.initials: A
authors.lastname: McGregor
authors.forename: Roberto
authors.initials: R
authors.lastname: Sorge
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Metcalfe
authors.forename: David M
authors.initials: DM
authors.lastname: Lloyd
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Dennison
mesh_terms: D000818:Animals; D001706:Biopsy; D050377:Cold Ischemia; D005112:Extracorporeal Circulation; D005260:Female; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D017114:Liver Failure, Acute / Q000628:therapy*; D008111:Liver Function Tests; D016015:Logistic Models; D009929:Organ Size; D010477:Perfusion / Q000379:methods*; D018709:Statistics, Nonparametric; D013552:Swine; D014159:Transducers; D052096:Warm Ischemia
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8