Levy Bruno, Desebbe Olivier, Montemont Chantal, Gibot Sebastien
Groupe CHOC, Contrat AVENIR INSERM 2006, Faculté de Médecine, Nancy Université, Vandoeuvre les Nancy, France.
Shock. 2008 Oct;30(4):417-21. doi: 10.1097/SHK.0b013e318167378f.
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.
在脓毒性休克期间，肌肉通过与肾上腺素刺激相关的、可能涉及β2肾上腺素能受体的、过度的钠钾 - 三磷酸腺苷酶（ATP酶）刺激的有氧糖酵解产生乳酸。因此，在低心输出量状态下，一定比例的高乳酸血症也与这种机制相关似乎是合乎逻辑的。因此，在低流量和正常至高流量的休克模型中，我们研究了：（1）肌肉是否产生乳酸；（2）肌肉乳酸产生是否与β2肾上腺素能刺激和钠钾ATP酶有关。我们在不同的啮齿动物休克模型（内毒素、腹膜炎和出血）中，使用微透析技术，通过非选择性和选择性β受体阻滞剂以及哇巴因，局部调节雄性Wistar大鼠骨骼肌中的肾上腺素能途径和钠钾ATP酶活性。通过乙醇清除率评估探针部位的血流量。我们测量了肌肉乳酸和血液乳酸浓度之间的差异，正梯度表明肌肉产生乳酸或丙酮酸。所有休克组的肾上腺素水平均升高。所有模型均伴有低血压和明显的高乳酸血症。肌肉乳酸浓度始终高于动脉水平，在内毒素休克中平均梯度为2.5±0.3，腹膜炎组为2.1±0.2 mM，出血性休克中为0.9±0.2 mM（所有组P<0.05）。肌肉丙酮酸浓度也始终高于动脉水平，在内毒素休克中平均梯度为260±40 μM，腹膜炎组为210±30 μM，出血性休克中为90±10 μM（所有组P<0.05）。尽管血流量减少，但所研究的所有药物制剂均降低了乳酸生成，而与休克机制无关。这表明休克状态下的乳酸产生至少部分与β2刺激下钠钾ATP酶活性增加有关。在与血流量减少或维持相关的休克状态下，肌肉乳酸释放的很大一部分是由β2受体刺激调节的，而非继发于氧供应减少。
