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Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers
Authors:Mathilde Steenks  Mark CPM van Baal  Vincent B Nieuwenhuijs  Menno T de Bruijn  Marc Schiesser  Mike H Teo  Tom Callahan  Rob TA Padbury  Greg J Barritt
Affiliation:1.Department of Medical Biochemistry, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, SA, Australia;2.The HPB and Liver Transplant Unit, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, SA, Australia;3.Department of Surgery, University Medical Centre, Groningen, The Netherlands;4.Discipline of Anatomical Sciences, Faculty of Health Sciences, University of Adelaide, SA, Australia
Abstract:

Background:

Ischaemic preconditioning (IPC) and intermittent ischaemia (INT) reduce liver injury after ischaemia reperfusion (IR). Steatotic livers are at a higher risk of IR injury, but the protection offered by IPC and INT is not well understood. The aim of the present study was to determine the effectiveness of IPC and INT in maintaining liver function in steatotic livers.

Material and methods:

A model of segmental hepatic ischaemia (45 min) and reperfusion (60 min) was employed using lean and obese Zucker rats. Bile flow recovery was measured to assess dynamic liver function, hepatocyte fat content quantified and blood electrolytes, metabolites and bile calcium measured to assess liver and whole body physiology. Liver marker enzymes and light and electron microscopy were employed to assess hepatocyte injury.

Results:

IPC was not effective in promoting bile flow recovery after IR in either lean or steatotic livers, whereas INT promoted good bile flow recovery in steatotic as well as lean livers. However, the bile flow recovery in steatotic livers was less than that in lean livers. In steatotic livers, ischaemia led to a rapid and substantial decrease in fat content. Steatotic livers were more susceptible to IR injury than lean livers, as indicated by increased blood ALT concentrations and major histological injury.

Conclusion:

INT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection.
Keywords:liver   ischaemia reperfusion injury   intermittent ischaemia   ischaemic preconditioning   bile flow   lipid   obese   rat
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