Bioenergetic targeting during organ preservation: P-31 magnetic resonance spectroscopy investigations into the use of fructose to sustain hepatic ATPturnover during cold hypoxia in porcine livers

During liver preservation, ATP supplies become depleted, leading to loss of cellular homeostatic controls and a cascade of ensuing harmful changes. An aerobic glycolysis is unable to prolong ATP production for a significant pe riod because of metabolic blockade. Our aim was to promote glycolysis durin g liver cold hypoxia by supplying fructose as an additional substrate, comp ared to supplementation with an equivalent concentration of glucose. Porcin e livers (two groups; n = 5 in each) were retrieved by clinical harvesting techniques and subjected to two cycles of cold hypoxia and oxygenated hypot hermic reperfusion. In the second cycle of reperfusion, the perfusate was s upplemented with either 10 mmol/L glucose (Group I)or 10 mmol/L fructose (G roup 2). During reperfusion in both groups, similar levels of ATP were dete cted by phosphorus magnetic resonance spectroscopy (P-31 MRS). However, dur ing subsequent hypoxia, ATP was detected for much longer periods in the fru ctose-perfused group. The rate of ATP loss was sevenfold slower during hypo xia in the presence of fructose than in the presence of glucose (ATP consum ption of -7.2 x 10 % total P-31 for Group 1 versus -1.0 x 10(-3)% total P-3 1 for Group 2: P < 0.001). The changes in ATP were mirrored by differences in other MRS-detectable intermediates: e.g., inorganic phosphate was signif icantly higher during subsequent hypoxia in Group 1 (45.7 +/- 2.7% total P- 31) than in Group 2 (33.7 +/- 1.1% total P-31: P < 0.01). High-resolution M RS of liver tissue extracts demonstrated that fructose was metabolized main ly via fructose 1-phosphate. We conclude that fructose supplied by brief hy pothermic perfusion may improve the bioenergeric status of cold hypoxic liv ers by sustaining anaerobic glycolysis via a point of entry into the pathwa y that is different from that for glucose. (C) 2000 Academic Press.