During liver preservation,
ATP supplies become depleted, leading to loss of cellular homeostatic controls and a cascade of ensuing harmful changes. Anaerobic glycolysis is unable to prolong
ATP production for a significant period because of metabolic blockade. Our aim was to promote glycolysis during liver cold
hypoxia by supplying
fructose as an additional substrate, compared to supplementation with an equivalent concentration of
glucose. Porcine livers (two groups; n = 5 in each) were retrieved by clinical harvesting techniques and subjected to two cycles of cold
hypoxia and oxygenated hypothermic reperfusion. In the second cycle of reperfusion, the perfusate was supplemented with either 10 mmol/
L glucose (Group 1) or 10 mmol/L
fructose (Group 2). During reperfusion in both groups, similar levels of
ATP were detected by
phosphorus magnetic resonance spectroscopy ((31)P MRS). However, during subsequent
hypoxia,
ATP was detected for much longer periods in the
fructose-perfused group. The rate of
ATP loss was sevenfold slower during
hypoxia in the presence of
fructose than in the presence of
glucose (
ATP consumption of -7.2 x 10(-3)% total (31)P for Group 1 versus -1.0 x 10(-3)% total (31)P for Group 2; P < 0. 001). The changes in
ATP were mirrored by differences in other MRS-detectable intermediates; e.g.,
inorganic phosphate was significantly higher during subsequent
hypoxia in Group 1 (45.7 +/- 2.7% total (31)P) than in Group 2 (33.7 +/- 1.1% total (31)P; P < 0. 01). High-resolution MRS of liver
tissue extracts demonstrated that
fructose was metabolized mainly via
fructose 1-phosphate. We conclude that
fructose supplied by brief hypothermic perfusion may improve the bioenergetic status of cold hypoxic livers by sustaining anaerobic glycolysis via a point of entry into the pathway that is different from that for
glucose.