PREMEDICATION WITH CYCLOSPORINE AND PERINDOPRIL MODIFIES THE ISCHEMIA-REPERFUSION INJURY DURING LIVER RESECTION IN RATS

The aim of the present study was to determine whether pretreatment wit h 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 d ays before ischaemia-reperfusion injury with liver resection). The isc haemia was produced by a 30 min continuous occlusion. The model was de signed to study liver function tests as the principal parameter. Compa red with liver resection only, bilirubin was significantly lower with perindopril on days 8 and 23, but significantly higher with CsA on day s 1 and 2. The alanine aminotransferase peak (day 1) was significantly lower with both perindopril and CsA. The prothrombin time was signifi cantly 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 his tology and bodyweight following an ischaemia-reperfusion injury associ ated with liver resection. These findings could limit ischaemia-reperf usion injury for major liver resections in the clinical setting.