Hypothermic Machine Preservation Attenuates Ischemia/Reperfusion Markers After Liver Transplantation: Preliminary Results

Guarrera, James V.; Henry, Scot D.; Chen, Sean W.C.; Brown, Tod; Nachber, Eugenia; Arrington, Ben; Boykin, Jason; Samstein, Benjamin; Brown, Robert S.; Emond, Jean C.; Lee, H. Thomas

doi:10.1016/j.jss.2010.01.038

« Previous Next »Journal of Surgical Research
Volume 167, Issue 2 , Pages e365-e373, 15 May 2011

Hypothermic Machine Preservation Attenuates Ischemia/Reperfusion Markers After Liver Transplantation: Preliminary Results

James V. Guarrera, M.D., F.A.C.S.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
- To whom correspondence and reprint requests should be addressed at 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.
Scot D. Henry, Ph.D.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Sean W.C. Chen, M.S.
- Department of Anesthesiology, Columbia University Medical Center, New York, New York
Tod Brown, B.S.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Eugenia Nachber, M.A.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Ben Arrington, B.S.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Jason Boykin
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Benjamin Samstein, M.D.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Robert S. Brown Jr., M.D., M.P.H.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
Jean C. Emond, M.D.
- Department of Surgery, Center for Liver Disease and Transplantation, Columbia University Medical Center, New York
H. Thomas Lee, M.D., Ph.D.
- Department of Anesthesiology, Columbia University Medical Center, New York, New York

Received 5 December 2009 published online 22 February 2010.

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.

Key Words: liver machine perfusion, liver transplantation, machine preservation, ischemia/reperfusion injury, tumor necrosis factor, interleukin-8, intracellular adhesion molecule-1