IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague–Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n=6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia, followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1±14.4% of baseline; P<0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P<0.05 compared with rats receiving I/R alone) and flow in HM (70.9±17.1% of baseline; P<0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8±122.3 compared with 5436.3±984.7 units/l respectively; P<0.01; aspartate aminotransferase, 630.8±76.9 compared with 3166.3±379.6 units/l respectively; P<0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.
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January 2005
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Research Article|
December 15 2004
Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis
Rahul S. KOTI;
Rahul S. KOTI
*University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London NW3 2QG, U.K.
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Wenxuan YANG;
Wenxuan YANG
*University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London NW3 2QG, U.K.
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Georgios GLANTZOUNIS;
Georgios GLANTZOUNIS
*University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London NW3 2QG, U.K.
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Alberto QUAGLIA;
Alberto QUAGLIA
†Academic Departments of Histopathology, Royal Free Hospital, London NW3 2QG, U.K.
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Brian R. DAVIDSON;
Brian R. DAVIDSON
*University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London NW3 2QG, U.K.
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Alexander M. SEIFALIAN
*University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London NW3 2QG, U.K.
Correspondence: Professor Alexander M. Seifalian (email [email protected]).
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Publisher: Portland Press Ltd
Received:
April 30 2004
Revision Received:
July 12 2004
Accepted:
September 02 2004
Accepted Manuscript online:
September 02 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 108 (1): 55–63.
Article history
Received:
April 30 2004
Revision Received:
July 12 2004
Accepted:
September 02 2004
Accepted Manuscript online:
September 02 2004
Citation
Rahul S. KOTI, Wenxuan YANG, Georgios GLANTZOUNIS, Alberto QUAGLIA, Brian R. DAVIDSON, Alexander M. SEIFALIAN; Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis. Clin Sci (Lond) 1 January 2005; 108 (1): 55–63. doi: https://doi.org/10.1042/CS20040130
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