Lactate levels in the brain are elevated upon exposure to volatile anesthetics: a microdialysis study

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.