title: An underlying mechanism for improved liver preservation with a combined histidine-lactobionate-raffinose flush solution.
abstract: In previous experimental liver transplant studies, it was possible to extend cold ischaemic time (CIT) by using a flush/storage solution combining histidine, lactobionate and raffinose (HLR). In this study, energy metabolism, glycolytic substrate (glucose) and anaerobic end-product (lactate) were examined in rat liver over 24 h of cold storage to determine the mechanism of action of the HLR solution. In livers subjected to simple flush and storage with the HLR solution, levels of ATP and ADP were considerably higher than livers stored with modified UW throughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1.1 and 3.1 mumol/g for HLR solution versus 0.18 and 0.81 mumol/g for UW solution. Total adenylate contents (TA = ATP + ADP + AMP) also remained 1-2 mumol/g higher in HLR-treated livers than those preserved in UW; TA values ranged from 3.8 to 5.7 mumol/g. Glucose increased to 20-35 mumol/g by 10-24 h of storage (similar to the UW group). Lactate rose to almost twice that in livers stored in UW; total lactate accumulation was approximately 10.0 mumol/g. This study demonstrated that the combined HLR solution is able to prolong the maximum 'safe' CIT by increasing anaerobic metabolism and consequently preserving liver energetics. The second part of the experiment examined the effect of continuous perfusion (with/without O2) over the 1st h of cold ischaemia. Under current methods of liver flushing and excision, the 1st h of cold storage may be the critical time of metabolic 'adjustment' since most of the pH and ATP changes occur during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University Department of Surgery, Royal Free Hospital & School of Medicine, London, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Churchill
authors.forename: C J
authors.initials: CJ
authors.lastname: Green
authors.forename: B R
authors.initials: BR
authors.lastname: Davidson
authors.forename: B J
authors.initials: BJ
authors.lastname: Fuller
mesh_terms: D000241:Adenosine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol; D000818:Animals; D004187:Disaccharides / Q000494:pharmacology; D004734:Energy Metabolism; D005978:Glutathione; D006019:Glycolysis; D006639:Histidine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin; D008099:Liver / Q000378:metabolism; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011887:Raffinose / Q000494:pharmacology; D051381:Rats
chemical_list: D004187:Disaccharides; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D006639:Histidine; D000493:Allopurinol; C005608:lactobionic acid; D000255:Adenosine Triphosphate; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose