Decreased loss of liver adenosine triphosphate during hypothermic preservation in rats pretreated with glucose: implications for organ donor management.
Recent studies of human donor livers indicate an association between ex vivo hepatocellular adenosine triphosphate and posttransplant graft function. To test the hypothesis that prior glucose loading of donor liver would optimize its adenosine triphosphate production and adenylate energy charge during ex vivo organ preservation, adult male rats were randomized to receive either intravenous dextrose or saline for 44 h. After this infusion, a liver lobe was exposed and freeze-clamped (time 0). The remaining liver was quickly flushed, excised, and stored in Collins' II solution at 2 degrees C for 8 h. Additional lobes were freeze-clamped at 1, 4, and 8 h. Liver adenosine triphosphate, total nucleoside triphosphates, and energy charge losses were significantly reduced in the dextrose-treated rats in comparison with saline-treated rats during the first 4 h of preservation. Although the livers from rats receiving intravenous dextrose were able to generate lactate, their glycogen stores were not utilized appreciably, suggesting that exogenous glucose served as a substrate for anaerobic glycolysis. Unesterified choline levels of the fasted rat livers were significantly higher than those from the rats receiving intravenous dextrose by the first hour, indicative of increased membrane breakdown. These results indicate that prior infusion of glucose enhances the capacity of the ex vivo liver, presumably through the induction and stabilization of key glycolytic enzymes, to anaerobically generate adenosine triphosphate. Administration of glucose to liver donors before organ procurement may improve post-transplant graft function by reducing the loss of hepatocellular energy, retarding membrane damage, and fostering glycogen storage for use in the early postoperative period.