Lactic Acidemla Caused by Endotoxin is Secondary to a Decrease in Clearance of Lactate. † 215

In patients with sepsis, high serum [lactate] have been associated with increased mortality. Lactic acidemia can be caused by an increase in the production of lactate or a decrease in clearance. Previous studies attempting to differentiate these two mechanisms of endotoxin (LPS) induced increase in serum [lactate] are inconclusive. In order to delineate between these two possiblities, we constantly infused tracer amounts of [14C]lactate into the IVC of chronically catheterized rats and determined the initial effect of LPS on blood [lactate] and the [14C]lactate. If there is an increase in production of lactate, the ratio of [14C]lactate:lactate ([14C]L/L) will decrease as blood [lactate] increases. However, if one assumes that [14C] lactate and endogenous lactate are similarly cleared, then a constant [14C]L/L associated with an increase in blood [lactate], will indicate a decrease in the clearance of lactate. 45 minutes after the start of the constant infusion of[14C]lactate (0.03 μCl/min) into the IVC, 6 μg/kg of LPS was infused into the IVC. Aortic blood samples were obtained -45, -15, -8, 0, 15, 30, 60, and 90 min after the LPS infusion. Aortic blood was deproteinized and analyzed for blood [lactate] (nmol/ml) using an enzymatic assay. [14C]lactate was isolated using a Dowex exchange column and [14C] was measured. In the four study rats, the serum [TNF] were elevated, 87±21 ng/ml indicating a response to LPS. Raw data were analyzed by ANOVA for repeated measures. In the following table values (mean±sem) were normalized to the average of the pre LPS levels.