title: Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion.
abstract: Liver transplantation is currently the only established treatment of end-stage liver disease, but it is limited by a severe shortage of viable donor livers. Donors after cardiac death (DCD) are an untapped source that could significantly increase the pool of available livers. Preservation of these DCD livers by conventional static cold storage (SCS) is associated with an unacceptable risk of primary nonfunction and delayed graft failure. Normothermic extracorporeal liver perfusion (NELP) has been suggested as an improvement over SCS. Livers recovered from male Lewis rats were subjected to 1 hr of warm ischemia and preserved with 5 hr of SCS or NELP, and transplanted into syngeneic recipients. As additional controls, non-ischemic livers preserved with 6 hr of SCS or NELP and unpreserved ischemic livers were transplanted. After NELP, ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 92% survival (n=13) after 4 weeks, which was comparable with control animals that received healthy livers preserved by SCS (n=9) or NELP (n=11) for 6 hr. On the other hand, animals from ischemia/SCS control group all died within 12 hr postoperatively (n=6). Similarly, animals that received ischemic livers without preservation all died within 24 hr after transplantation (n=6). These results suggest that NELP has the potential to reclaim warm ischemic livers that would not be transplantable otherwise. The rat model in this study is a useful platform to further optimize NELP as a method of recovery and preservation of DCD livers.
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Tolboom
authors.forename: Roos E
authors.initials: RE
authors.lastname: Pouw
authors.forename: Maria-Louisa
authors.initials: ML
authors.lastname: Izamis
authors.forename: Jack M
authors.initials: JM
authors.lastname: Milwid
authors.forename: Nripen
authors.initials: N
authors.lastname: Sharma
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
authors.forename: François
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D002470:Cell Survival; D005112:Extracorporeal Circulation; D006085:Graft Survival; D008099:Liver / Q000098:blood supply / Q000201:enzymology / Q000473:pathology / Q000601:surgery*; D008102:Liver Circulation; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation; D010101:Oxygen Consumption; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin