SCIENTIfIC REpoRts | (2018) 8:4405 | DOI:10.1038/s41598-018-22689-9
Organ-specic responses during
brain death: increased aerobic
metabolism in the liver and
anaerobic metabolism with
decreased perfusion in the kidneys
A. C. Van Erp
, R. A. Rebolledo
, D. Hoeksma
, N. R. Jespersen
, P. J. Ottens
, R. Nørregaard
, C. Laustsen
, J. G. M. Burgerhof
, J. C. Wolters
, J. Ciapaite
, H. E. Bøtker
H. G. D. Leuvenink
& B. Jespersen
Hepatic and renal energy status prior to transplantation correlates with graft survival. However, eects
of brain death (BD) on organ-specic energy status are largely unknown. We studied metabolism,
perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD
was induced in mechanically-ventilated rats, inating an epidurally-placed Fogarty-catheter, with sham-
operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-
related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated
and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry
was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression
(P-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased
gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal
perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex
I/ATP synthase activity were unaected. In conclusion, the liver responds to increased metabolic
demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift
towards anaerobic energy production while renal perfusion decreases. Our ndings highlight the need
for an organ-specic approach to assess and optimise graft quality prior to transplantation, to optimise
hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxication.
e shortage of donor organs suitable for transplantation remains a major healthcare challenge. Despite various
strategies to expand the donor pool, such as the increased use of non-heart beating, or living donor gras
organs transplanted worldwide are still obtained from brain-dead donors
. However, compared to living donor
transplantation, transplantation of brain-dead organ gras leads to higher rejection rates and inferior long-term
. us, the current challenge is to use all available organs including the suboptimal and concurrently
improve transplantation outcomes.
Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
Institute for Medical
and Biological Engineering, Schools of Engineering, Biological Sciences and Medicine, Ponticia Universidad Católica
de Chile, Santiago, Chile.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Clinical Medicine, Aarhus University, Aarhus, Denmark.
MR Research Center, Clinical Institute, Aarhus University,
Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
Department of Analytical Biochemistry, Research Institute of Pharmacy, University of Groningen, Groningen, The
Systems Biology Centre for Energy Metabolism and Ageing, University of Groningen, Groningen,
Department of Paediatrics, University Medical Center Groningen, Groningen, The Netherlands.
Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. A. C. Van Erp and R. A. Rebolledo
contributed equally to this work. Correspondence and requests for materials should be addressed to A.C.V.E. (email:
Received: 19 July 2017
Accepted: 28 February 2018
Published: xx xx xxxx