Comparison of energy metabolism in liver grafts from donors after circulatory death and donors after brain death during cold storage and reperfusion.
BACKGROUND
Donation after circulatory death (DCD) liver grafts have supplemented the donor organ pool, but certain adverse outcomes have prevented exploration of the full potential of such organs. The aim of this study was to determine key differences in basic energy metabolism between DCD and donation after brainstem death (DBD) grafts.


METHODS
Microdialysis samples from DCD and DBD allograft parenchyma from cold storage to 48 h after reperfusion were analysed by colorimetric methods. Interstitial lactate, pyruvate and glycerol levels were measured and the lactate/pyruvate ratio was calculated to estimate energy depletion of the grafts. Histological features of ischaemia and reperfusion injury were assessed.


RESULTS
Donor age, extent of steatosis and cold ischaemia time were comparable between ten DCD and 20 DBD organs. DCD grafts had higher levels of interstitial lactate (median 11.6 versus 1.2 mmol/l; P = 0.015) and increased lactate/pyruvate ratio (792 versus 38; P = 0.001) during cold storage. There was no significant difference in glycerol levels between DCD and DBD grafts (225.1 versus 127.5 µmol/l respectively; P = 0.700). Rapid restoration of energy levels with lactate clearance, increased pyruvate levels and reduced lactate/pyruvate ratio was seen following reperfusion of functioning DCD grafts, parallel with levels in DBD grafts. Histology revealed more pronounced glycogen depletion in DCD grafts. Three allografts that failed owing to primary non-function showed energy exhaustion with severe glycogen depletion.


CONCLUSIONS
Liver grafts from DCD donors exhibited depletion of intracellular energy reserves during cold storage. Failed allografts showed severe energy depletion. Modified organ preservation techniques to minimize organ injury related to altered energy metabolism may enable better utilization of donor organs after circulatory death.
Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK.
M T P R
MT
Perera
D A
DA
Richards
M A
MA
Silva
N
N
Ahmed
D A
DA
Neil
N
N
Murphy
D F
DF
Mirza
D000328:Adult; D000368:Aged; D001926:Brain Death; D015925:Cryopreservation / Q000379:methods*; D004734:Energy Metabolism / Q000502:physiology*; D005990:Glycerol / Q000378:metabolism; D006085:Graft Survival; D006323:Heart Arrest; D006801:Humans; D007511:Ischemia / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D016031:Liver Transplantation; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D019289:Pyruvic Acid / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D013997:Time Factors
D019344:Lactic Acid; D019289:Pyruvic Acid; D005990:Glycerol