Abstract
The authors conducted a prospective, randomized study to investigate the effects of an intraportal glucose-insulin infusion during the donor operation for ortho-topic human liver transplantation on hepatic glycogen deposition before cold preservation as well as on hepatic glycogen utilization and liver function after transplantation. Control donors received no special treatment, whereas donors in the experimental group received an infusion of 20% dextrose containing 20 mEq of potassium chloride and 100 IU of Humulin (Eli Lilly, Indianapolis, IN) via the inferior mesenteric vein initiated at the beginning of the donor operation. The infusion rate was started at 10 mL/kg per hour for 6 minutes. Then another 100 IU of Humulin was added to the remaining solution and the infusion rate halved to 5 mL/kg per hour throughout the remainder of the procedure until the time of vascular cross clamping. Arterial blood glucose concentrations were monitored every 15 minutes by glucometer and maintained between 12 and 14 mmol/L. Five liver biopsies were sequentially taken at the following times: (1) at the beginning of the donor operation before portal glucose infusion was initiated; (2) immediately after cold flush with University of Wisconsin solution (end of the donor operation); (3) on removal of the liver from the ice (the end of the cold ischemic time); (4) immediately before portal vein reperfusion (the end of the warm ischemia time); and (5) 1 hour after portal vein unclamping. Specimens were frozen in liquid nitrogen and stored for glycogen assay and light microscopy. Blood was drawn daily from liver recipients for the first 5 days after transplantation. Peak aspartate aminotransferase concentration was used as the main marker for liver preservation injury.
Sixteen donors in each group were studied. There were no cases of primary graft nonfunction, recipient deaths, or complications as a result of the protocol or liver biopsies. The glucose-insulin infusion significantly increased glycogen deposition in donor livers (4.2 ± 0.9 g/ 100 g of dry liver weight per hour), whereas liver glycogen content in controls decreased during the donor operation. New glycogen was deposited predominantly in zones 1 and 2 of the liver lobule. Liver glycogen was consumed during all phases of liver transplantation, with the greatest rate of utilization in the reperfusion period, a lesser rate in the warm ischemic period, and the lowest rate in the cold ischemic period. Liver glycogen utilization by glucose-infused livers significantly exceeded that by control livers during all phases of transplantation. The mean initial and peak aspartate aminotransferase concentrations were significantly less in the glucose-infused group, demonstrating a protective effect of liver glycogenation on cold preservation and reperfusion injury of the liver. The rate of glycogen deposition during the donor operation and the rate of glycogen utilization during warm ischemia were significantly associated with less liver injury. Well-glycogenated livers were well protected from injury during prolonged warm ischemia, and this effect was particularly noticeable in livers from donors less than 30 years of age.
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