title: Comparing early liver graft function from heart beating and living-donors: A pilot study aiming to identify new biomarkers of liver injury.
abstract: The liver and kidney functions of recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemia times were examined during the neohepatic phase for the elimination of rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods. Metabolomics and the relative expressions of miR-122, miR-148a and γ-glutamyltranspeptidase (GGT), liver injury biomarkers, were also measured. The ROC clearance for HBD was significantly lower than that for LD (0.147 ± 0.052 vs. 0.265 ± 0.148 ml·min-1·g-1liver) after intravenous injection (0.6 mg·kg-1). The clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg·kg-1·h-1), was similar between HBD and LD groups (~ 1 ml·min-1·kg-1). The TXA clearance in both groups was lower than the GFR, showing a small extent of hepatorenal coupling. The miR-122 and miR-148a expressions were similar for the HBD and LD groups, whereas GGT expression was significantly increased for HBD. The lower ROC clearance and the higher GGT levels in the HBD group of longer cold ischemia times performed worse than the LD group during the neophase. Metabololmics further showed clusters of bile acids, phospholipids and lipid ω-oxidation products for the LD and HBD groups. In conclusion, ROC CL and GGT expression, and metabolomics could serve as sensitive indices of early graft function. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Canada.
authors.forename: Qi Joy
authors.initials: QJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kluger
authors.affiliation: Department of Chemistry, University of Waterloo, Canada.|Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Goryński
authors.affiliation: Department of Chemistry, University of Waterloo, Canada.
authors.forename: Janusz
authors.initials: J
authors.lastname: Pawliszyn
authors.affiliation: Department of Chemistry, University of Waterloo, Canada.|Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bojko
authors.affiliation: Departments of Biochemistry and Molecular Medicine, Comprehensive Cancer Center, UC Davis, Davis, CA, 95817, USA.
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Canada.
authors.forename: Keumhan
authors.initials: K
authors.lastname: Noh
authors.affiliation: Department of Surgery, Toronto General Hospital, University Health Network, Toronto, ON, M5G 2N2, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.|Department of Anesthesia, Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1E2, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Jerath
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.|Department of Anesthesia, Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1E2, Canada.
authors.forename: Stuart
authors.initials: S
authors.lastname: McCluskey
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Canada.
authors.forename: K Sandy
authors.initials: KS
authors.lastname: Pang
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.|Department of Anesthesia, Faculty of Medicine, University of Toronto, Toronto, ON, M5G 1E2, Canada.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wąsowicz
mesh_terms: D000328:Adult; D000368:Aged; D000732:Androstanols / Q000097:blood / Q000493:pharmacokinetics; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D017093:Liver Failure / Q000235:genetics / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D055432:Metabolomics; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D010865:Pilot Projects; D000077123:Rocuronium; D014019:Tissue Donors; D014148:Tranexamic Acid / Q000097:blood / Q000493:pharmacokinetics; D005723:gamma-Glutamyltransferase / Q000235:genetics
chemical_list: D000732:Androstanols; D015415:Biomarkers; C531907:MIRN122 microRNA, human; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D014148:Tranexamic Acid; D005723:gamma-Glutamyltransferase; D000077123:Rocuronium
keywords: biomarkers and metabolomics; heart beating and living donors; liver and kidney function; liver transplantation; rocuronium bromide and tranexamic acid clearance