Bioenergetic targeting during organ preservation: (31)P magnetic resonance spectroscopy investigations into the use of fructose to sustain hepatic ATP turnover 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. 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.
Changani
K K
KK
Department of Surgery, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2QG, United Kingdom.
Fuller
B J
BJ
Bell
J D
JD
Taylor-Robinson
S
S
Davidson
B R
BR
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000693:Anaerobiosis; D000818:Animals; D001706:Biopsy; D015687:Cell Hypoxia; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects*; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007036:Hypothermia, Induced; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D009926:Organ Preservation / Q000379:methods*; D010100:Oxygen / Q000494:pharmacology; D010759:Phosphorus Isotopes / Q000032:analysis*; D015424:Reperfusion; D012107:Research Design; D013552:Swine
D010759:Phosphorus Isotopes; D005632:Fructose; D000255:Adenosine Triphosphate; D010100:Oxygen