Brief communication Enhanced energy metabolism during cold hypoxic organ preservation: studies on rat liver after pyruvate supplementation q Po-Wah So a and Barry J. Fuller b, * a Imperial College School of Medicine, Biological Imaging Centre, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK b University Department of Surgery, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG, UK Received 13 February 2003; accepted 8 May 2003 Abstract Previous studies have indicated that pyruvate is able to reduce ischaemia/reperfusion (I/R) injury in a variety of tissues, but a full understanding of the effects is lacking. In this current preliminary study, magnetic resonance spec- troscopy (MRS) was used to investigate the biochemical effects of differing concentrations of pyruvate (3 and 15 mM) on liver metabolism during the cold hypoxic preservation period itself, in order to gain insight into possible mecha- nisms. Hepatic lactate, alanine, and succinate levels were increased in livers preserved with 15 mM pyruvate added to the University of Wisconsin (UW) solution and were generally elevated (but to a lesser degree) in livers flushed with 3 mM pyruvate, compared to those cold stored in UW alone. Further, from enzymatic assays of adenine nucleotides, 15 mM levels of pyruvate were found to maintain higher ATP levels during short periods (up to 4 h) of cold hypoxic storage than in UW stored livers, whilst energy charge ratios (after 4 and 24 h) were also higher (P < 0:01 in each case). This may arise from enhanced glycolysis secondary to an improved redox status in the pyruvate-treated livers, as ev- ident by the increase in the levels of lactate. Ó 2003 Elsevier Science (USA). All rights reserved. Pyruvate is a three-carbon a-keto acid and a major metabolic intermediate linking glycolysis and the Krebs cycle in the cellular production of energy. It plays a central role in the inter-conver- sion of carbohydrates, lipid, and amino acids in both catabolic and anabolic reactions. Pyruvate has been shown to possess protective effects against pathological changes in a variety of tissues during ischaemia/reperfusion injury (I/R) includ- ing heart [3], intestine [5], and kidney [10]. An additional effect of pyruvate has been attributed to an oxygen free radical (OFR)-scavenging role. The molecule can react in a stoichiometric and non- enzymatic fashion with hydrogen peroxide, thus preventing redox cycling of peroxide through OFR species which ultimately cause cell damage [1]. In studies on isolated hepatocytes, administration of pyruvate was shown to reduce I/R injury at nor- mal body temperatures [2]. Interestingly, the effects q Parts of this study were funded by Wellcome Trust Grant 056648/2/99/2 to B.J.F. * Corresponding author. Fax: +44-020-7431-4528. E-mail address: b.fuller@rfh.ucl.ac.uk (B.J. Fuller). Cryobiology 46 (2003) 295–300 www.elsevier.com/locate/ycryo 0011-2240/03/$ - see front matter Ó 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0011-2240(03)00047-6