Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats

Schiesser, Marc; Wittert, Anna; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T.A.; Barritt, Greg J.

doi:10.1016/j.jss.2008.01.007

« Previous Next »Journal of Surgical Research
Volume 152, Issue 1 , Pages 61-68, March 2009

Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats

Marc Schiesser, M.D.
- The HPB and Liver Transplant Unit, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia
Anna Wittert, M.D.
- The HPB and Liver Transplant Unit, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia
Vincent B. Nieuwenhuijs, M.D., Ph.D.
- University Medical Centre, Groningen, The Netherlands
Arthur Morphett, F.R.C.P.A., M.B.B.S.
- Department of Anatomical Pathology, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia
Robert T.A. Padbury, F.R.A.C.S., M.B.B.S.
- The HPB and Liver Transplant Unit, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia
Greg J. Barritt, Ph.D.
- Department of Medical Biochemistry, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, South Australia, Australia
- To whom correspondence and reprint requests should be addressed at Department of Medical Biochemistry, School of Medicine, Flinders University, GPO Box 2100, Adelaide SA 5001, Australia

Received 24 October 2007 published online 12 May 2008.

Background/Aims

Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of this study was to investigate the effects of IPC and INT on ischemia reperfusion injury in aged livers.

Methods

A rat model of segmental hepatic ischemia (45 min) and reperfusion (60 min) was used. Bile flow, as an indicator of early hepatocyte damage and dynamic liver function, plasma concentrations of bilirubin, liver marker enzymes, and liver histology were assessed.

Results

In young rats (8–13 weeks), IPC regimes of 10 min clamping and 10 min reperfusion, and 5 min clamping and 30 min reperfusion, restored bile flow to 23 and 42%, respectively, of the initial value, compared to 14 and 88% for continuous clamping and controls, respectively. An INT regime of three cycles of alternating 15 min perfusion and 15 min clamping gave a substantially greater (70%) restoration of bile flow. In aged rats (20–24 months), the IPC regimes did not give any restoration of bile flow. By contrast, the INT regime restored bile flow to 68%. Plasma bilirubin concentrations were lowest in the INT groups, whereas alanine transaminase concentrations for the IPC and INT groups compared with the continuous clamping groups showed no significant differences.

Conclusions

In young rats, INT is more effective than IPC in restoring the immediate consequences of IP-induced damage to hepatocytes and liver function after ischemia-reperfusion. In aged rats INT, but not IPC, reverses hepatocyte damage and restores liver function. INT may promote better hepatocyte and liver function than IPC following the surgical resection of aged livers.

Key Words: liver, ischemia reperfusion injury, intermittent ischemia, bile flow, aged, rat