Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers.
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.


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.


CONCLUSIONS
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.
Steenks
Mathilde
M
Department of Medical Biochemistry, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, SA, Australia.
van Baal
Mark C P M
MC
Nieuwenhuijs
Vincent B
VB
de Bruijn
Menno T
MT
Schiesser
Marc
M
Teo
Mike H
MH
Callahan
Tom
T
Padbury
Rob T A
RT
Barritt
Greg J
GJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004573:Electrolytes / Q000097:blood; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D019194:Ischemic Preconditioning; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery / Q000648:ultrastructure; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors
D015415:Biomarkers; D004573:Electrolytes; D000410:Alanine Transaminase; D002118:Calcium