FUNCTIONAL-CHARACTERISTICS OF THE HYPERMETABOLIC ISOLATED-PERFUSED LIVER

Clinically, hypermetabolism of the liver accompanies the systemic resp onse associated with trauma and sepsis, Although increased metabolism is generally considered a beneficial response, a markedly increased he patic oxygen consumption (HVO2) may be associated with adverse consequ ences such as induction of centrilobular hypoxia, We studied the effec ts of lactate and glucagon as inducers of increased HVO2 in the isolat ed perfused rat liver to determine if hepatic functional derangements could be precipitated by these trauma-associated factors at high metab olic rates. HVO2 rose by 27%, 52%, and 70% in response to 5 mM lactate /1 mM pyruvate, 20 nM glucagon, or both, respectively. In response to these stimuli at a fixed perfusion rate, hepatic venous oxygen saturat ion declined to 48 +/- 4% at the highest HVO2, and this was associated with a reduced hepatic adenosine triphosphate content and fibrinogen secretion. These findings indicate that hepatic metabolic disturbances can result from hepatocellular hypoxia due to increased HVO2.