During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 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-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta 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+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<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 beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.
The use of norepinephrine was associated with improved mean arterial pressure, sustained aortic and mesenteric blood flow, and better tissue oxygenation when compared with fluid resuscitation alone, irrespective of time of administration. The early use of norepinephrine plus volume expansion was associated with a higher proportion of blood flow redistributed to the mesenteric area, lower lactate levels, and less infused volume. Thus, the early use of norepinephrine is safe and may decrease the need for volume resuscitation.
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