Comparison of thermal variations in post-retrieval graft conditioning on rat livers

Background: Machine perfusion was found an effective tool to recover organ grafts from ischemic insults during preservation. It could be observed that organ integrity is significantly affected by abrupt temperature shifts during hypothermic storage and implantation periods. Studies showed that a gentle and controlled rise of the temperature during oxygenated machine perfusion prior to implantation can protect the tissue from reperfusion injury. Now, the possible role of temperature kinetics upon retrieval of the graft and prior to later cold storage should be investigated. Methods: Rat livers were retrieved after cardiac arrest and subjected to a brief ex situ machine perfusion with either hypothermic resuscitation (HR) at 8 degrees C, near-normothermic resuscitation (NR) at 30 degrees C or progressive resuscitation with lowering the temperature in a controlled fashion from 30 degrees C to 8 degrees C (PR). After cold storage (CS), liver functional parameters were evaluated by an established ex vivo reperfusion system. Results: NR and PR resulted in significantly lower release of hepatic enzymes and less production of tumor necrosis factor upon reperfusion compared to CS while HR had a far less protective effect. An increase in bile production was only observed in the PR group, which also significantly increased the recovery of tissue adenosine triphosphate, the amount of which was, however, nearly paralleled by the NR protocol. Conclusion: Within the limitations of this model, it seems that normothermic recirculation appears to be a superior approach for the restitution of warm-ischemically injured liver grafts than immediate hypothermic machine perfusion.