Molecular Medicine

, Volume 21, Issue 1, pp 833–846 | Cite as

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

  • Pim B. Olthof
  • Megan J. Reiniers
  • Marcel C. Dirkes
  • Thomas M. van Gulik
  • Michal Heger
  • Rowan F. van Golen
Review Article


Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided.



The authors thank Inge Kos from the medical illustration service for some of the artwork. RF van Golen was supported by a PhD scholarship and the Young Talent Fund, both from the Academic Medical Center in Amsterdam. M Heger was supported by grants from the Dutch Anti-Cancer Foundation (Stichting Nationaal Fonds Tegen Kanker) in Amsterdam, the Phospholipid Research Center in Heidelberg, the Nijbakker-Morra Foundation in Leiden, and Stichting Technologische Wetenschap (STW).


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Authors and Affiliations

  • Pim B. Olthof
    • 1
  • Megan J. Reiniers
    • 1
  • Marcel C. Dirkes
    • 1
  • Thomas M. van Gulik
    • 1
  • Michal Heger
    • 1
  • Rowan F. van Golen
    • 1
  1. 1.Department of Experimental Surgery, Surgical Laboratory, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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