Continuous infusion ofN-acetylcysteine reduces liver warm ischaemia–reperfusion injury

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Abstract
Background: N‐acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia–reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model. Methods: Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment. Results: Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared with that in the IR group (P = 0·023). Hepatic microcirculation improved after 5 h of reperfusion (P = 0·036) and liver injury was reduced after 5 h, as indicated by alanine aminotransferase activity (P = 0·007) and indocyanine green clearance (uptake, P = 0·001; excretion, P = 0·032). Conclusion: The main protective effect of NAC becomes apparent 5 h after hepatic ischaemic injury. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.