AN UNDERLYING MECHANISM FOR IMPROVED LIVER PRESERVATION WITH A COMBINED HISTIDINE-LACTOBIONATE-RAFFINOSE FLUSH SOLUTION

In previous experimental liver transplant studies, it was possible to extend cold ischaemic time (CIT) by using a flush/storage solution com bining histidine, lactobionate and raffinose (HLR). In this study, ene rgy metabolism, glycolytic substrate (glucose) and anaerobic end-produ ct (lactate) were examined in rat liver over 24 h of cold storage to d etermine the mechanism of action of the HLR solution. In livers subjec ted to simple flush and storage with the HLR solution, levels of ATP a nd ADP were considerably higher than livers stored with modified UW th roughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1 .1 and 3.1 mu mol/g for HLR solution versus 0.18 and 0.81 mu mol/g for UW solution. Total adenylate contents (TA = ATP + ADP + AMP) also rem ained 1-2 mu mol/g higher in HLR-treated livers than those preserved i n UW; TA values ranged from 3.8 to 5.7 mu mol/g. Glucose increased to 20-35 mu mol/g by 10-24 h of storage (similar to the UW group), Lactat e rose to almost twice that in livers stored in UW; total lactate accu mulation was approximately 10.0 mu mol/g. This study demonstrated that the combined HLR solution is able to prolong the maximum 'safe' CIT b y increasing anaerobic metabolism and consequently preserving liver en ergetics. The second part of the experiment examined the effect of con tinuous perfusion (with/without O-2) over the 1st h of cold ischaemia. Under current methods of liver flushing and excision, the Ist h of co ld storage may be the critical time of metabolic 'adjustment' since mo st of the pH and ATP changes occur during this period. Therefore, we t ested the hypothesis that the combination of a simple flush with an ad ditional brief 1-h perfusion period prior to storage would enhance the maintenance of hepatic energetics. There was no beneficial effect of 1 h of perfusion without O-2 compared to simple HLR flush and storage. However, perfusion with O-2 resulted in prolonged maintenance of high energy adenylates and total adenylates; at 10 h of storage ATP was 1. 0, ADP 3.3, and TA 5.7 mu mol/g. However, any improvement in ultimate viability following long-term storage of the livers in these two group s needs to be tested in an animal transplant model.