DONOR NUTRITIONAL-STATUS - A DETERMINANT OF LIVER PRESERVATION INJURY

In liver transplantation, the quality of the liver is determined by a number of factors including donor nutritional status, Livers from fast ed donors appear to tolerate long-term preservation better than livers from fed donors, In this study we repeated earlier results and obtain ed 31% (4/13) survival after 40-hr preservation of livers from fed don or Brown Norway rats and 67% (8/12) survivors with donor livers from 4 -day-fasted rats (P=0.154), The explanation for this improvement is no t known but may be due to inactivation of Kupffer cells due to nutriti onal depletion of the liver, Kupffer cell activation has been one expl anation advanced to explain how cold storage injures livers during rep erfusion (transplantation). In this study, we have measured how donor fasting affects Kupffer cell function (phagocytosis of colloidal carbo n) after preservation of the rat liver, In addition, we measured how e nhancing liver glycogen by feeding glucose to the rat donors affected outcome and liver functions tested by isolated perfusion after 24- and 40-hr cold storage of the liver, Preservation did not cause inactivat ion or activation of Kupffer cell phagocytosis of colloidal carbon, In livers with 0-hr preservation, colloidal carbon uptake was 3.1+/-0.2 mg/g/hr, after 40-hr preservation uptake was 3.8 mg/g/hr (P<0.05 vs. 0 hr) (fed) and 2.7+/-0.3 mg/g/hr (fasted, P, 0.05 vs. 0-hr and 40-hr-f ed), Thus, the improved survival obtained with livers from fasted dono rs does not appear related to inactivation of Kupffer cell phagocytosi s, Although livers from fasted donors showed improved survival, there was extensive hepatocellular injury as indicated by large LDH release from the livers after 40-hr cold storage as tested by isolated perfusi on, LDH released into the perfusate increased from 35.8+/-10.1 U/L (fe d, 40-hr CS) to 301+/-65 U/L (fasted, 40-hr CS) after 1-hr reperfusion , AST release showed a similar pattern and bile production was suppres sed more in livers from fasted donors than fed donors, Feeding rats gl ucose elevated liver glycogen and significantly reduced hepatocellular injury as measured by LDH release and AST release in the isolated per fused liver after 40-hr cold storage, Feeding rats glucose (40% in dri nking water for 4 days) also improved survival: fed + glucose = 85% su rvival versus 31% survival with no glucose and fasted + glucose = 92% survival versus 67% survival with no glucose. These results show that both extensive donor fasting and glucose feeding enhanced outcome in o rthotopic liver transplantation. This dilemma (both fasting and feedin g improved survival) are discussed in terms of how the interactions be tween Kupffer cells and hepatocytes affect liver viability. Donor fast ing is probably impractical clinically as a method to improve the dono r liver, but elevating liver glycogen by glucose supplementation is po ssible and may lead to improved preservation and outcome in liver tran splantation.