title: Premedication with cyclosporine and perindopril modifies the ischaemia-reperfusion injury during liver resection in rats.
abstract: The aim of the present study was to determine whether pretreatment with cyclosporine (CsA), or perindopril (an angiotensin converting enzyme inhibitor) would modify the ischaemia-reperfusion injury of vascular occlusion during liver resection. Rats were allocated to four groups (n = 20 for each group): (i) sham operated; (ii) liver resection only; (iii) CsA (15 mg/kg); and (iv) perindopril (4 mg/kg during the three days before ischaemia-reperfusion injury with liver resection). The ischaemia was produced by a 30 min continuous occlusion. The model was designed to study liver function tests as the principal parameter. Compared with liver resection only, bilirubin was significantly lower with perindopril on days 8 and 23, but significantly higher with CsA on days 1 and 2. The alanine aminotransferase peak (day 1) was significantly lower with both perindopril and CsA. The prothrombin time was significantly less on days 2 and 4 with perindopril and day 4 with CsA. Liver histological changes were minimal in all groups at 30 min ischaemia, but were significantly less severe in the perindopril group. There was a significant decrease in the weight of the regenerated liver at day 23 with perindopril and a significantly lower drop in weight on day 1 and the rate of gain was significantly greater. Perindopril (4 mg/kg) and CsA (15 mg/kg) significantly alter liver function tests, liver histology and bodyweight following an ischaemia-reperfusion injury associated with liver resection. These findings could limit ischaemia-reperfusion injury for major liver resections in the clinical setting.
authors.affiliation: University of Melbourne, Department of Surgery, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Hardy
authors.forename: S
authors.initials: S
authors.lastname: Tancheroen
authors.forename: A
authors.initials: A
authors.lastname: Shulkes
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001835:Body Weight; D016572:Cyclosporine / Q000627:therapeutic use*; D006498:Hepatectomy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size; D020913:Perindopril; D011292:Premedication; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D016572:Cyclosporine; D001663:Bilirubin; D020913:Perindopril