title: A bioartificial liver support system using primary hepatocytes: a preclinical study in a new porcine hepatectomy model.
abstract: BACKGROUND
  Bioartificial liver support systems providing a bridge to transplantation or even a definitive treatment of acute hepatic failure are a current focus of research. Different devices are used, although an impact on patient survival is doubtful for the time being. After developing a new flat membrane bioreactor, further preclinical studies have become necessary. Existing animal models of fulminant hepatic failure show common difficulties in defining a reproducible loss of functional liver tissue while considering systemic side effects. We now present a reproducible model with total hepatectomy in pigs, suitable to test the safety and efficacy of liver support systems.
  
  
  METHODS
  Twelve pigs underwent total hepatectomy by using silicone tubes and a Y-adapter as vascular prosthesis; intracranial pressure was measured via a subdural probe. Anhepatic pigs were monitored under general anesthesia until death occurred. All were treated with a new flat membrane bioreactor (FMB) that contained porcine hepatocytes in 6 of the 12 cases.
  
  
  RESULTS
  Our hepatectomy technique proved to be successful without requiring venovenous bypass circulation. Mean vascular clamping time was 9 minutes. The mean survival time was longer in animals treated with hepatocyte-equipped bioreactors than in untreated animals (24.8 +/- 4.3 vs 16.4 +/- 4.7 hours), which already showed increased intracranial pressure after 10 to 12 hours. Serum albumin levels indicated stable cell-specific functions of the FMB.
  
  
  CONCLUSIONS
  The described technique of total hepatectomy is a well-reproducible animal model. The presented FMB maintained stable cell-specific functions and is a safe and efficient device.
authors.affiliation: Department of General Surgery and Transplantation, University of Essen, Germany.
authors.forename: Nils R
authors.initials: NR
authors.lastname: Frühauf
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Oldhafer
authors.forename: Maike
authors.initials: M
authors.lastname: Höltje
authors.forename: Gernot M
authors.initials: GM
authors.lastname: Kaiser
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Frühauf
authors.forename: Gregor A
authors.initials: GA
authors.lastname: Stavrou
authors.forename: Augustinus
authors.initials: A
authors.lastname: Bader
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Broelsch
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects*; D022781:Hepatocytes / Q000502:physiology*; D017114:Liver Failure, Acute / Q000209:etiology / Q000628:therapy*; D019164:Liver, Artificial; D008567:Membranes, Artificial; D023421:Models, Animal; D015203:Reproducibility of Results; D013552:Swine; D016896:Treatment Outcome
chemical_list: D008567:Membranes, Artificial