Hepatic oxygen and lactate extraction during stagnant hypoxia

As O₂ delivery falls, tissues must extract increasing amounts of O₂ from blood to maintain a normal O₂ consumption. Below a critical delivery threshold, increases in O₂ extraction cannot compensate for the falling delivery, and O₂ uptake falls in a supply-dependent fashion. Numerous studies have identified a critical delivery in whole animals, but the regional contributions to the critical O₂ delivery are less fully understood. In the present study, we explored the limits of O₂ extraction in the isolated liver, seeking to determine 1) the normal relationship between O₂ consumption and delivery in the liver and 2) the relationship of hepatic lactate extraction to the drop in hepatic O₂ consumption at low O₂ deliveries. To answer these questions, using support dogs as a source for oxygenated metabolically stable blood, we studied eight pump-perfused canine livers. By lowering the blood flow in a model of stagnant hypoxia, we explored the relationship between O₂ consumption and delivery over the entire physiological range of O₂ delivery. The critical O₂ delivery was 28 ±5 (SD) ml·kg^-1·min^-1; the livers extracted 68 ± 9% of the delivered O₂ before reaching supply dependence. This suggests that the liver has an O₂ extraction capacity quite similar to the body as a whole and not different from other tissues that have been isolated. At high blood flows, the livers extracted ~10% of the lactate delivered by the blood, but the arteriovenous lactate differences were small. At low blood flows, however, the livers changed from lactate consumption to production. The O₂ delivery coinciding with the dropoff in lactate extraction did not differ significantly from the critical O₂ delivery. We conclude that reductions in lactate uptake by the liver do not precede the transition to O₂ supply dependence.