title: Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation.
abstract: BACKGROUND
  Utilizing livers from donors after cardiac death could significantly expand the donor pool. We have previously shown that normothermic (37°C) extracorporeal liver perfusion significantly improves transplantation outcomes of ischemic rat livers. Here we investigate whether recovery of ischemic livers is possible using sub-normothermic machine perfusion at 20°C and 30°C.
  
  
  METHODS
  Livers from male Lewis rats were divided into five groups after 1 h of warm ischemia (WI): (1) WI only, (2) 5 h of static cold storage (SCS), or 5 h of MP at (3) 20°C, (4) 30°C, and (5) 37°C. Long-term graft performance was evaluated for 28 d post-transplantation. Acute graft performance was evaluated during a 2 h normothermic sanguineous reperfusion ex vivo. Fresh livers with 5 h of SCS were positive transplant controls while fresh livers were positive reperfusion controls.
  
  
  RESULTS
  Following machine perfusion (MP) (Groups 3, 4, and 5), ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 100% survival (N ≥ 4) after 4 wk. On the other hand, animals from WI only, or WI + SCS groups all died within 24 h of transplantation. Fresh livers preserved using SCS had the highest alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the lowest bile production during reperfusion, while at 28 d post-transplantation, livers preserved at 20°C and 30°C had the highest total bilirubin values.
  
  
  CONCLUSIONS
  MP at both 20°C and 30°C eliminated temperature control in perfusion systems and recovered ischemically damaged rat livers. Postoperatively, low transaminases suggest a beneficial effect of sub-normothermic perfusion, while rising total bilirubin levels suggest inadequate prevention of ischemia- or hypothermia-induced biliary damage.
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Tolboom
authors.forename: Maria-Louisa
authors.initials: ML
authors.lastname: Izamis
authors.forename: Nripen
authors.initials: N
authors.lastname: Sharma
authors.forename: Jack M
authors.initials: JM
authors.lastname: Milwid
authors.forename: Basak
authors.initials: B
authors.lastname: Uygun
authors.forename: François
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D007511:Ischemia / Q000628:therapy*; D008099:Liver / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D052096:Warm Ischemia