Digestive Diseases and Sciences

, Volume 51, Issue 6, pp 1087–1102

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

  • Vincent B. Nieuwenhuijs
  • Menno T. De Bruijn
  • Robert T. A. Padbury
  • Gregory J. Barritt
Liver

DOI: 10.1007/s10620-006-8014-y

Cite this article as:
Nieuwenhuijs, V.B., Bruijn, M.T.D., Padbury, R.T.A. et al. Dig Dis Sci (2006) 51: 1087. doi:10.1007/s10620-006-8014-y

Abstract

Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2 +, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2 + in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.

Keywords

liver bile flow ischemia-reperfusion injury ischemic preconditioning fatty liver intracellular Ca2 + 

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Vincent B. Nieuwenhuijs
    • 1
  • Menno T. De Bruijn
    • 1
    • 2
  • Robert T. A. Padbury
    • 1
  • Gregory J. Barritt
    • 2
    • 3
  1. 1.HPB and Liver Transplant UnitFlinders UniversityBedford ParkAustralia
  2. 2.Medical Biochemistry Flinders Medical Centre and School of MedicineFlinders UniversityBedford ParkAustralia
  3. 3.Department of Medical Biochemistry, School of MedicineFlinders UniversityAdelaideAustralia

Personalised recommendations