THE EFFECTS OF AGING AND NUTRITIONAL STATE ON HYPOXIA-REOXYGENATION INJURY IN THE PERFUSED-RAT-LIVER

During liver transplantation, donor livers are subject to hypoxia and reoxygenation. Recently, because of a shortage of suitable donors, the livers of older donors have been used for transplantation. In this study, we examined the influence of aging and nutritional state on hepatic intracellular pH (pH(i)) and the susceptibility of the rat liver to hypoxia-reoxygenation injury. Perfused livers from fasted and fed, young (23 months) and aged (24-28 months) male Wistar rats were compared during 30 min of nitrogen hypoxia followed by 20 min of reoxygenation. Under control conditions, pH(i) was significantly lower and glucose release higher in livers from fed young rats (7.24+/-0.04, 3.4+/-1.8 mu mol/min/g) than in those from fasted young (7.33+/-0.04, 0.0+/-1.3), fasted aged (7.32+/-0.03, -0.1+/-0.5), and fed aged rats (7.29+/-0.06, 0.9+/- 1.0). In all groups, pH(i) fell by similar to 0.15 U during hypoxia. Lactate dehydrogenase (LDH) release from the livers of fed young livers was unaffected by hypoxia-reoxygenation as was that from the livers of fed aged rats, despite features that would be expected to predispose to injury (reduced glucose output and more alkaline pH(i)). In contrast, livers from fasted young and aged rats had substantially increased LDH release and reduced bile flow during hypoxia. There were no age-related differences in these parameters, but, during reoxygenation, LDH release was significantly less in the aged livers. These results indicate that the livers of fed rats are resistant to hypoxia-reoxygenation injury and that aging does not increase the susceptibility of the liver to injury in the fasted state.