Mitochondrial DNA levels in perfusate and bile during ex vivo normothermic machine correspond with donor liver quality
Lauren P. Westhaver,
Sarah Nersesian,
Riley J. Arseneau,
Joshua Hefler,
Breanna K.V. Hargreaves,
Alexander Edgar,
Yara Azizieh,
Nerea Cuesta-Gomez,
Dayne L. Izquierdo,
A.M. James Shapiro,
Boris L. Gala-Lopez,
Jeanette E. Boudreau
Affiliations
Lauren P. Westhaver
Department of Pathology, Dalhousie University, Halifax, NS, Canada
Sarah Nersesian
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
Riley J. Arseneau
Department of Pathology, Dalhousie University, Halifax, NS, Canada
Joshua Hefler
Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
Breanna K.V. Hargreaves
Dalhousie Medical School NS, Dalhousie University, Halifax, NS, Canada
Alexander Edgar
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
Yara Azizieh
Department of Pathology, Dalhousie University, Halifax, NS, Canada
Nerea Cuesta-Gomez
Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
Dayne L. Izquierdo
Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
A.M. James Shapiro
Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
Boris L. Gala-Lopez
Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Department of Surgery, Dalhousie University, Halifax, NS, Canada
Jeanette E. Boudreau
Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Corresponding author. Department of Microbiology and Immunology Room 7C, Sir Charles Tupper Medical Building 5850 College St. Halifax, NS, Canada B3H 4H7
Ex vivo normothermic machine perfusion (NMP) preserves donor organs and permits real-time assessment of allograft health, but the most effective indicators of graft viability are uncertain. Mitochondrial DNA (mtDNA), released consequent to traumatic cell injury and death, including the ischemia-reperfusion injury inherent in transplantation, may meet the need for a biomarker in this context. We describe a real time PCR-based approach to assess cell-free mtDNA during NMP as a universal biomarker of allograft quality. Measured in the perfusate fluid of 29 livers, the quantity of mtDNA correlated with metrics of donor liver health including International Normalized Ratio (INR), lactate, and warm ischemia time, and inversely correlated with inferior vena cava (IVC) flow during perfusion. Our findings endorse mtDNA as a simple and rapidly measured feature that can inform donor liver health, opening the possibility to better assess livers acquired from extended criteria donors to improve organ supply.
