title: Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis.
abstract: 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.
authors.affiliation: University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, The Royal Free Hospital, London NW3 2QG, U.K.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Koti
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Yang
authors.forename: Georgios
authors.initials: G
authors.lastname: Glantzounis
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008833:Microcirculation; D023421:Models, Animal; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000255:Adenosine Triphosphate