Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation.

During septic shock, muscle produces lactate by way of an exaggerated NaKYadenosine triphosphatase (ATPase)Ystimulated aerobic glycolysis associated with epinephrine stimulation possibly through "2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-highYflow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to "2 adrenergic stimulation and Na K-ATPase. We locally modulated the adrenergic pathway and NaK-ATPase activity in male Wistar rats’ skeletal muscle using microdialysis with nonselective and selective " blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5 T 0.3 in endotoxic shock, 2.1 T 0.2 mM in peritonitis group, and 0.9 T 0.2 mM in hemorrhagic shock (P G 0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260 T 40 2M in endotoxic shock, 210 T 30 2M in peritonitis group, and 90 T 10 2M in hemorrhagic shock (P G 0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under "2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a "2 receptor stimulation and not secondary to a reduced oxygen availability. KEYWORDS—Sepsis, animal model, hypoxia, glycolysis, lactic acid, epinephrine