Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results.
BACKGROUND
Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function.


METHODS
We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. Liver allografts underwent HMP for 4-7 h using dual centrifugal perfusion with Vasosol solution at 4-8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism.


RESULTS
We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP.


CONCLUSIONS
HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.
Guarrera
James V
JV
Department of Surgery, Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, 622 West 168th Street PH 14 Center, Room 202, New York, NY 10032, USA. jjg46@columbia.edu
Henry
Scot D
SD
Chen
Sean W C
SW
Brown
Tod
T
Nachber
Eugenia
E
Arrington
Ben
B
Boykin
Jason
J
Samstein
Benjamin
B
Brown
Robert S
RS
Emond
Jean C
JC
Lee
H Thomas
HT
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D006801:Humans; D007036:Hypothermia, Induced / Q000295:instrumentation* / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016031:Liver Transplantation / Q000502:physiology*; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D016209:Interleukin-8; D019188:Organ Preservation Solutions; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1