title: Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers.
abstract: Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. Liver Transplantation 22 979-993 2016 AASLD.
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, MO.
authors.forename: Babak
authors.initials: B
authors.lastname: Banan
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.|Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Rao
authors.initials: R
authors.lastname: Watson
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, MO.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, MO.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Departments of Surgery, Washington University School of Medicine, St. Louis, MO.
authors.forename: William
authors.initials: W
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts / Q000473:pathology; D062005:Biopsy, Large-Core Needle; D002331:Carnitine / Q000627:therapeutic use; D046148:Donor Selection / Q000379:methods; D000077270:Exenatide; D005234:Fatty Liver / Q000188:drug therapy; D005260:Female; D006801:Humans; D008099:Liver; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D010477:Perfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013696:Temperature; D014022:Tissue Survival; D014688:Venoms / Q000627:therapeutic use; D052096:Warm Ischemia
chemical_list: D019188:Organ Preservation Solutions; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D002331:Carnitine