title: Hypothermic Oxygenated Perfusion (HOPE) downregulates the immune response in a rat model of liver transplantation.
abstract: OBJECTIVE
  To evaluate the impact of a novel oxygenated perfusion approach on rejection after orthotopic liver transplantation (OLT).
  
  
  BACKGROUND
  Hypothermic oxygenated perfusion (HOPE) was designed to prevent graft failure after OLT. One of the mechanisms is downregulation of Kupffer cells (in situ macrophages). We, therefore, designed experiments to test the effects of HOPE on the immune response in an allogeneic rodent model of nonarterialized OLT.
  
  
  METHODS
  Livers from Lewis rats were transplanted into Brown Norway rats to induce liver rejection in untreated recipients within 4 weeks. Next, Brown Norway recipients were treated with tacrolimus (1 mg/kg), whereas in a third group, liver grafts from Lewis rats underwent HOPE or deoxygenated machine perfusion for 1 hour before implantation, but recipients received no immunosuppression. In a last step, low-dose tacrolimus treatment (0.3 mg/kg) was assessed with and without HOPE.
  
  
  RESULTS
  Allogeneic OLT without immunosuppression led to death within 3 weeks after nonarterialized OLT due to severe acute rejection. Full-dose tacrolimus prevented rejection, whereas low-dose tacrolimus led to graft fibrosis within 4 weeks. HOPE treatment without immunosuppression also protected from lethal rejection. The combination of low-dose tacrolimus and 1-hour HOPE resulted in 100% survival within 4 weeks without any signs of rejection.
  
  
  CONCLUSIONS
  We demonstrate that allograft treatment by HOPE not only protects against preservation injury but also impressively downregulates the immune system, blunting the alloimmune response. Therefore, HOPE may offer many beneficial effects, not only to rescue marginal grafts but also by preventing rejection and the need for immunosuppression.
authors.affiliation: *Laboratory of the Swiss HPB and Transplant Center, Department of Surgery, University Hospital Zurich, Switzerland †Hospital Paul Brousse, Université Paris Sud, Paris, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schlegel
authors.forename: Philipp
authors.initials: P
authors.lastname: Kron
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Clavien
authors.forename: Philipp
authors.initials: P
authors.lastname: Dutkowski
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D006084:Graft Rejection / Q000276:immunology*; D007036:Hypothermia, Induced; D007728:Kupffer Cells / Q000276:immunology*; D016031:Liver Transplantation; D010100:Oxygen; D010477:Perfusion / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control; D015996:Survival Rate; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D010100:Oxygen; D016559:Tacrolimus