Energy metabolism following prolonged hepatic cold preservation: Benefits of interrupted hypoxia on the adenine nucleotide pool in rat liver

The ability of brief hypothermic reperfusion (HtR) to restore hepatic energ y metabolism following periods of cold hypoxic preservation was studied in isolated rat livers after storage times of 5, 10, and 24 h. In addition, in vestigations were performed on the effects of HtR used to restore Liver oxi dative metabolism in the middle of a prolonged (24 h) hypoxic preservation period. A histidine-lactobionate-raffinose solution was used for the initia l cold portal flush in all groups. Results showed that cold hypoxia for eit her 5 or 10 h yielded livers capable of similar recoveries of ATP, energy c harge, and total adenine nucleotides, but that HtR after 24 h cold preserva tion resulted in reduced regeneration of ATP, a lower energy charge, and a fall in tissue adenine nucleotides. When Livers were stead for 24 h but sub jected to brief HtR after either 5 or 10 h before return to hypoxic storage , improved recoveries of the energy metabolites were seen over those record ed after 24 h hypoxia alone. The fact that these improvements were not due to an improved supply of adenine nucleotide precursors was demonstrated by studying groups which were given HtR with perfusate containing precursors o f adenine nucleotides (adenosine, adenine, and inosine) after 24 h cold hyp oxia. These data are consistent with the hypothesis that poor metabolic rec overy after long-term hepatic cold preservation results more from decreased mitochondrial oxidative phosphorylation than from a lack of precursors for adenine nucleotide resynthesis. In addition, restoring oxidative metabolis m at hypothermia for brief periods can to some extent protect final metabol ic status after prolonged storage. (C) 1999 Academic Press.