A global approach to energy metabolism in an experimental model of sepsis

Disturbances in energy metabolism during sepsis are not clearly understood. The aim of the study was to globally assess the energy drive in septic rat myocytes, studying both glycolysis rates and mitochondrial maximal activit ies together, using recent fn vitro techniques. Measurements were assessed before (H0) and. 4 h after sepsis induction (H4). Hyperlactatemia was obser ved in all septic animals ([lactate] = 1.2 +/- 0.3 mmol/L at H0 versus 3.3 +/- 0.6 mmol/L at H4; p < 0.001). An enhanced glycolysis rate was observed in both aerobic (J(A) = 7.2 +/- 0.9 at H0 versus 18.2 +/- 4.1 nmol glucose/ min/g at H4; p < 0.05) and anaerobic (J(B) = 7.5 +/- 1.2 at H0 versus 15.4 +/- 3.4 p,mol glucose/min/g at H4; p < 0.05) fluxes, associated with a sele ctive significant pyruvate-malate-dependent oxygen consumption rate decreas e (Vo(2)-PM = 0.144 +/- 0.008 at H0 versus 0.113 +/- 0.007 mu mol O-2/h/mg at H4; p < 0.05). This oxygen consumption decrease can be interpreted eithe r as a complex I and/or a complex I-ubiquinone relation alteration. Our res ults are consistent with the hypothesis that an altered mitochondrial funct ion during sepsis is responsible, at least in part, for hyperlactatemia, wh ich is thus a consequence of an increased glycolysis rate.