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Protective mechanisms of end-ischemic cold machine perfusion in DCD liver grafts.
MedLine Citation:
PMID:  23063573     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND & AIMS: The aim of this study was to identify protective mechanisms of cold machine perfusion in liver grafts donated after cardiac death. METHODS: Pig livers exposed to 60 min warm ischemia were cold stored for 7 h or treated after 6 h cold storage by 1 h hypothermic oxygenated perfusion (HOPE) through the portal vein. Different physical (perfusion pressure) and chemical (oxygen, mitochondrial transition pore inhibition) parameters were analyzed during machine perfusion to dissect key steps of mechanism. RESULTS: HOPE treatment led to a significant slow-down of mitochondrial respiration rate during 1h machine perfusion. After reperfusion following low pressure HOPE, mitochondrial injury, nuclear injury, Kupffer-cell activation and endothelial injury were significantly improved, as tested on an isolated liver perfusion model. In contrast, machine perfusion with deoxygenated perfusate showed no protection from hepatocyte injury and Kupffer-cell activation. However, endothelial injury was also prevented by low pressure machine perfusion in the absence of oxygen. Perfusion with higher pressure provoked endothelial damage and Kupffer-cell activation. CONCLUSIONS: The mechanisms of protection by hypothermic machine perfusion appear to be at least two fold. First, oxygenation under hypothermic conditions protects from mitochondrial and nuclear injury by down regulation of mitochondrial activity before reperfusion. Second, cold perfusion itself, under low pressure conditions, prevents endothelial damage, independently from oxygen.
Authors:
O de Rougemont; A Schlegel; R Graf; P-A Clavien; P Dutkowski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Journal of hepatology     Volume:  -     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Swiss HPB and Transplant Center, Department of Surgery, University Hospital Zurich.
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