Biochemical appraisal of models for hepatic ischemia-reperfusion injury

Since total hepatic ischemia occurs with transplantation, there has been interest in developing a model which could be used to evaluate interventions to mitigate hepatic ischemic injury. The initial model employed global ischemia of the entire liver which necessitated the placement of a portal-femoral shunt (model A). In 1982, a model of hepatic ischemia was proposed in which ischemia was produced only in the left and median lobes which obviated the need for the shunt (model B). Recently, it has been found that with this model, increased flow to the nonischemic right lobe persists after left reperfusion thus effectively "stealing" blood from the reperfusing left lobe. Occlusion (model C) or removal (model D) of the right lobe on reperfusion have been proposed as techniques to reduce the "steal". We found, that after 30 min of ischemia, the ATP recovery for model B was significantly slower than for either model C or D. Similarly, the AMP content of model B lobes was significantly higher after 15 min of reperfusion, while 30 min after reperfusion, the total adenine nucleotide content was significantly lower in model B compared with models C and D. The energy charge returned to normal within 15 min of reperfusion in model C lobes while it was delayed until 60 min of reperfusion for models B and D. This study provides support for the advantages of right lobe occlusion (model C) over model B for acute studies evaluating the effect of interventions on ischemic injury to the liver and of removal (model D) for survival studies.