[Trimetazidine prevents ischemia-reperfusion injury in hepatic surgery under vascular clamping]. The role of allopurinol in human liver ischemia/reperfusion injury: a prospective randomized clinical trial. Protective effect of prostaglandin E1 against ischemia/reperfusion-induced liver injury: results of a prospective, randomized study in cirrhotic patients undergoing subsegmentectomy.
Clamping the hepatic pedicle (or Pringle's manoeuvre) is frequently used to reduce blood loss during liver surgery. This induces a normothermic ischaemia of the overall liver. In this study we have investigated the anti-ischaemic effect of trimetazidine during surgery on hydatid cysts of the liver requiring vascular clamping of the hepatic pedicle. Seventy-six hepatic pericystectomies were performed under a 40 min normothermic ischaemia. Two randomized groups including 38 patients each received daily either trimetazidine (80 mg/kg, group 1) or placebo (group 2) for 5 days before surgery. The effect of trimetazidine was evaluated on different parameters, the macroscopic appearance of the tissue, the ATP content in liver biopsies obtained before and after 15, 30 and 60 min reperfusion, the activity of the aminotransferase in the plasma and the plasma concentrations of reduced and oxidized gluthatione. No mortality was observed. The duration of hospital stay was reduced for patients treated with trimetazidine (8 +/- 1 days compared with 11 +/- 1.5 days for patients in group 2; p < 0.05). Morbidity rate was lower in group 1 (11 per cent) than in group 2 (18.5 per cent) but the decrease was not significant. Trimetazidine treatment reduced cytolysis (p < 0.05 on day 1, day 3, day 5), increased liver ATP content and limited the increase of reduced and oxidized gluthatione in the plasma during reperfusion. These results suggest that trimetazidine alleviates ischaemia-reperfusion injury during liver surgery and may allow extension of the ischaemic period without damage to the liver. To investigate the effect of pretreatment with allopurinol on oxidative stress during reperfusion and the role in liver tissue protection in partial liver resections for colorectal cancer metastases confined to the liver.
                Prospective, randomized, clinical trial, single center, Leiden University Medical Center, The Netherlands.
                Curative partial liver resection of colorectal metastases in 16 patients with or without allopurinol pretreatment, between June 1992 and February 1994.
                Partial liver resections with Pringle maneuver, intravenous allopurinol versus no allopurinol.
                The effect of allopurinol on liver cell damage caused by ischemia/reperfusion studied by measuring malondialdehyde, glutathione, glutathione disulfide, vitamin C, liver enzymes and blood clotting factors in blood samples. Morbidity and mortality were also evaluated.
                Pretreatment with allopurinol had no significant effect on any of our study parameters.
                Because ischemia/reperfusion damage is little in our study, pretreatment with allopurinol is of no value. The cytoprotective effects of prostaglandin E1 on livers suffering from ischemia/reperfusion injury in the clinical setting are unproved. These effects were examined, focusing on inflammatory cytokine and nitric oxide metabolism.
                Twenty-four cirrhotic patients with hepatocellular carcinoma undergoing subsegmentectomy under ischemia induced only by Pringle's maneuver were divided into two groups (patients given prostaglandin E1 by injection and untreated controls) and postoperative results were compared. Peripheral blood was taken perioperatively and the plasma aminotransferase, cytokines and nitrate/nitrite levels of the two groups were compared. Two liver specimens were taken from each patient, one before ischemia and the other after hepatectomy, and the levels of inducible nitric oxide synthase and cytokine mRNAs and proteins were analyzed.
                Although no apparent differences were recognized in postoperative complications or duration of postoperative hospital stay between the groups, the perioperative plasma aminotransferase level was significantly lower in the prostaglandin E1 group. Significant differences were also seen in interleukin-6 and nitrate plasma levels during the observation period and the interleukin-6 protein levels in the liver supernatants after hepatectomy in the two groups. In contrast, no significant differences were apparent between the interleukin-1 beta and tumor necrosis factor-alpha plasma levels of the two groups. The corrected fluorescence activities of interleukin-6 and inducible nitric oxide synthase mRNAs in the liver after hepatectomy correlated significantly. No interleukin-1 beta or tumor necrosis factor-alpha mRNAs or proteins were detected.
                Prostaglandin E1 exerted hepatoprotective effects on livers suffering from ischemia/reperfusion injury, and interleukin-6 might play an important role in these effects.
Ulinastatin may have a protective effect against ischaemia reperfusion injury relative to gantaile in elective liver resections performed under vascular occlusion. The absolute benefit of this drug agent remains unknown. None of the drugs can be recommended for routine clinical practice. Considering that none of the drugs have proven to be useful to decrease ischaemia reperfusion injury, such trials should include a group of patients who do not receive any active intervention whenever possible to determine the pharmacological drug's absolute effects on ischaemia reperfusion injury in liver resections.