Ischemia-reperfusion injury is more severe in older versus young rat livers

Background. Hepatic warm ischemia during surgery remains a significant problem, particularly in organs with possible baseline dysfunction. The objective of this study was to investigate whether age influences the degree of warm ischemia-reperfusion injury in rat livers. Materials and methods. The left and median lobes of young (3 months) and adult (9 months) male rats were exposed to 75 min of ischemia followed by reperfusion. Each age group was divided into two sub-groups. One sub-group was observed for 8 h, whereas the other was allowed to survive. Animals in the 8-h groups (young and adult) were sacrificed, and blood and tissue were taken to determine liver enzymes, neutrophil accumulation, and blood metabolic profiles and to examine the histology. Results. Hepatocellular injury was significantly greater in adult rats after 8 h of reperfusion, as determined by hepatic enzyme levels and histology. Liver enzyme levels were massively elevated in adult rats and were significantly higher compared with those of young rats. The degree of necrosis and neutrophil accumulation was significantly higher in adult rats. After 8 h of reperfusion, the metabolic profiling of the blood revealed elevated levels of creatine, creatinine, allantoin, and amino acids (tyrosine, methionine) in the adult rats. At 24 h of reperfusion, all adult rats died, in contrast to young rats, which all survived. Conclusions. Aging in rats is associated with greater hepatocellular injury and poor survival rate after 75 min of warm hepatic ischemia. (c) 2007 Elsevier Inc. All rights reserved.