Premedication with cyclosporine and perindopril modifies the ischaemia-reperfusion injury during liver resection in rats.
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.
Hardy
K J
KJ
University of Melbourne, Department of Surgery, Austin Hospital, Heidelberg, Victoria, Australia.
Tancheroen
S
S
Shulkes
A
A
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*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D016572:Cyclosporine; D001663:Bilirubin; D020913:Perindopril