Age-related hepatic tolerance to ischemia-reperfusion injury in a rat model of extended hepatectomy

Purpose Hepatic ischemia-reperfusion injury remains an important cause of liver dysfunction after major liver surgery. Whether the immature liver responds to prolonged warm ischemia in the same way as the more mature liver is not well defined. This study assessed age-related differences in liver injury in a rat model of extended hepatectomy with vascular exclusion. Methods Male Wistar rats aged 3, 6, 9, and 12 weeks underwent approximately 70% hepatectomy with 60 min of vascular exclusion followed by reperfusion. Survival, serum biochemical markers, semi-quantitative histological injury scores, and hepatic malondialdehyde concentration were assessed. Histological data were analyzed using mixed-effects models with animal identity included as a random effect. Results Early mortality was high, and overall survival did not differ significantly between age groups. Postoperative biochemical analysis was limited by the small number of surviving animals and was interpreted descriptively. The cumulative histological injury score showed the most consistent age-related pattern. In the mixed-effects model, cumulative injury was associated with age group, operative stage, and the age-by-stage interaction. The main difference was observed after 60 min of ischemia followed by 30 min of reperfusion, when 3-week-old rats had lower cumulative injury scores than older animals. Individual histological components and MDA values were less consistent and were considered supportive findings. Conclusion In this severe model of warm ischemia-reperfusion combined with extended hepatectomy, younger rats showed lower cumulative histological injury scores than more mature animals, particularly during the reperfusion phase. These findings suggest that developmental age may influence hepatic tolerance to ischemic stress, but they should be interpreted as experimental and hypothesis-generating rather than directly applicable to clinical ischemia limits in children.