title: Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.
abstract: BACKGROUND
  Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored.
  
  
  METHODS
  DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation.
  
  
  RESULTS
  Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups.
  
  
  CONCLUSIONS
  Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania. Electronic address: dbezinover@hmc.psu.edu.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Bezinover
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Ramamoorthy
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Postula
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Gregory
authors.initials: G
authors.lastname: Weller
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Saifeldin
authors.initials: S
authors.lastname: Mahmoud
authors.affiliation: Department of Pathology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.affiliation: Department of Transplant Surgery, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Zakiyah
authors.initials: Z
authors.lastname: Kadry
authors.affiliation: Department of Transplant Surgery, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Berend
authors.initials: B
authors.lastname: Mets
authors.affiliation: Department of Anesthesiology, Virginia Commonwealth University Medical Center, Richmond, Virginia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Spiess
authors.affiliation: Genome Sciences Core Facility, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Robert
authors.initials: R
authors.lastname: Brucklacher
authors.affiliation: Genome Sciences Core Facility, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Willard
authors.initials: W
authors.lastname: Freeman
authors.affiliation: Department of Anesthesiology, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D050377:Cold Ischemia; D004195:Disease Models, Animal; D005466:Fluorocarbons; D008107:Liver Diseases / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D017202:Myocardial Ischemia / Q000401:mortality / Q000473:pathology; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D014021:Tissue Preservation
chemical_list: D005466:Fluorocarbons; C008805:perfluorodecalin; D000255:Adenosine Triphosphate; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Cold perfusion; DCD liver grafts; Gene expression; Perfluorocarbons