Department of Pharmacology, College of Pharmacy, Biocenter, Goethe University, Frankfurt am Main, Germany.
Neurochem Int. 2010 Dec;57(8):940-7. doi: 10.1016/j.neuint.2010.09.014. Epub 2010 Oct 7.
Anesthetic agents have well-defined pharmacological targets but their effects on energy metabolism in the brain are poorly understood. In this study, we examined the effects of different anesthetics on extracellular lactate and glucose levels in blood, CSF and brain of the mouse. In vivo-microdialysis was used to monitor extracellular energy metabolites in the brain of awake mice and during anesthesia with seven different anesthetic drugs. In separate groups, lactate and glucose concentrations in blood and CSF were measured for each anesthetic. We found that anesthesia with isoflurane caused a large increase of extracellular lactate levels in mouse striatum and hippocampus (300-400%). Pyruvate levels also increased while glucose and glutamate levels were unchanged. This effect was dose-dependent and was mimicked by other gaseous anesthetics such as halothane and sevoflurane but not by intravenous anesthetics. Ketamine/xylazine and chloral hydrate caused 2-fold increases of glucose levels in mouse blood and brain while lactate levels were only moderately increased. Propofol caused a minor increase of extracellular glucose levels while pentobarbital had no effect on either lactate or glucose. Volatile anesthetics also increased lactate levels in blood and CSF by 2-3-fold but had no effect on plasma glucose. Further experiments demonstrated that lactate formation by isoflurane in mouse brain was independent of neuronal impulse flow and did not involve ATP-dependent potassium channels. We conclude that volatile anesthetics, but not intravenous anesthetics, cause a specific, dose-dependent increase in extracellular lactate levels in mouse brain. This effect occurs in the absence of ischemia, is independent of peripheral actions and is reflected in strongly increased CSF lactate levels.
麻醉剂具有明确的药理学靶点，但它们对大脑能量代谢的影响知之甚少。在这项研究中，我们研究了不同麻醉剂对小鼠血液、CSF 和大脑中细胞外乳酸和葡萄糖水平的影响。使用活体微透析监测清醒小鼠和使用七种不同麻醉药物麻醉时大脑中的细胞外能量代谢物。在单独的组中，测量了每种麻醉剂的血液和 CSF 中的乳酸和葡萄糖浓度。我们发现，异氟烷麻醉导致小鼠纹状体和海马细胞外乳酸水平大幅升高（300-400%）。丙酮酸水平也升高，而葡萄糖和谷氨酸水平保持不变。这种效应呈剂量依赖性，并且被其他气态麻醉剂（如氟烷和七氟醚）模拟，但不被静脉麻醉剂模拟。氯胺酮/二甲苯胺和水合氯醛导致小鼠血液和大脑中的葡萄糖水平增加了 2 倍，而乳酸水平仅适度增加。丙泊酚导致细胞外葡萄糖水平轻微增加，而戊巴比妥对乳酸或葡萄糖均无影响。挥发性麻醉剂也使血液和 CSF 中的乳酸水平增加了 2-3 倍，但对血浆葡萄糖没有影响。进一步的实验表明，异氟烷在小鼠大脑中形成的乳酸独立于神经元冲动流，不涉及 ATP 依赖性钾通道。我们得出结论，挥发性麻醉剂（而非静脉麻醉剂）会导致小鼠大脑中细胞外乳酸水平特异性、剂量依赖性增加。这种效应发生在没有缺血的情况下，独立于外周作用，并且反映在强烈增加的 CSF 乳酸水平中。
