Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

Larach, Daniel B.; Kofke, W. Andrew; Roux, Peter Le

doi:10.1007/s12028-011-9517-8

Cited by 47 publications

(39 citation statements)

References 125 publications

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“…2 Because cytoplasmic lactate and pyruvate readily exchange with extracellular fluids (including blood and perfusion media 3 ), the lactate/ pyruvate ratio (LPR) is considered a reliable index of intracellular cytoplasmic redox state, the [ [3][4][5] Microdialysate LPRs are very useful but not diagnostically specific. 6 Poor outcome after TBI is associated with low oxygen, glucose, pyruvate levels, high LPR, and elevated glutamate and glycerol levels, particularly when changes have longer duration and higher magnitude. [7][8][9][10] Probe Site Microdialysis catheter location is important, e.g., in gray or white matter ipsilateral or contralateral to the injury because metabolite level changes are larger in lesioned or penumbral zones compared with distant 'normal' tissue.…”

Section: Brain Microdialysis After Traumatic Brain Injurymentioning

confidence: 99%

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Dienel

2014

J Cereb Blood Flow Metab

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Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as 'preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte-neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted.

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Section: Brain Microdialysis After Traumatic Brain Injurymentioning

confidence: 99%

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Dienel

2014

J Cereb Blood Flow Metab

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“…A lactate/pyruvate (L/P)-ratio over 40 is known as a marker for tissue ischemia (11,12). In our study the L/P-ratio was greater than 40 during the first day of the study in the tumor tissue in eight patients (Table 1).…”

Section: Lactate/pyruvate Ratio At Baseline and During The Ketogenic mentioning

confidence: 50%

Decline of Lactate in Tumor Tissue After Ketogenic Diet: In Vivo Microdialysis Study in Patients with Head and Neck Cancer

Schroeder

Himpe

Pries

et al. 2013

Nutrition and Cancer

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In head and neck squamous cell carcinoma (HNSCC) aerobic glycolysis is the key feature for energy supply of the tumor. Quantitative microdialysis (μD) offers an online method to measure parameters of the carbohydrate metabolism in vivo. The aim was to standardize a quantitative μD-study in patients with HNSCC and to prove if a ketogenic diet would differently influence the carbohydrate metabolism of the tumor tissue. Commercially available 100 kDa-CMA71-μD- catheters were implanted in tumor-free and in tumor tissue in patients with HNSCC for simultaneous measurements up to 5 days. The metabolic pattern and circadian rhythm of urea, glucose, lactate, and pyruvate was monitored during 24 h of western diet and subsequent up to 4 days of ketogenic diet. After 3 days of ketogenic diet the mean lactate concentration declines to a greater extent in the tumor tissue than in the tumor-free mucosa, whereas the mean glucose and pyruvate concentrations rise. The in vivo glucose metabolism of the tumor tissue is clearly influenced by nutrition. The decline of mean lactate concentration in the tumor tissue after ketogenic diet supports the hypothesis that HNSCC tumor cells might use lactate as fuel for oxidative glucose metabolism.

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“…The increase in glycolytic rate causes a massive production of lactate and increase in the LP ratio although tissue pyruvate remains at a normal level or increases slightly (Figure 12B). Under clinical conditions, an increase in LP ratio may be caused by a variety of mechanisms (201). Drugs that are effective in mitochondrial dysfunction are presently under investigation.…”

Section: Cerebral Energy Metabolismmentioning

confidence: 99%

Aspects on the Physiological and Biochemical Foundations of Neurocritical Care

2017

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Neurocritical care (NCC) is a branch of intensive care medicine characterized by specific physiological and biochemical monitoring techniques necessary for identifying cerebral adverse events and for evaluating specific therapies. Information is primarily obtained from physiological variables related to intracranial pressure (ICP) and cerebral blood flow (CBF) and from physiological and biochemical variables related to cerebral energy metabolism. Non-surgical therapies developed for treating increased ICP are based on knowledge regarding transport of water across the intact and injured blood–brain barrier (BBB) and the regulation of CBF. Brain volume is strictly controlled as the BBB permeability to crystalloids is very low restricting net transport of water across the capillary wall. Cerebral pressure autoregulation prevents changes in intracranial blood volume and intracapillary hydrostatic pressure at variations in arterial blood pressure. Information regarding cerebral oxidative metabolism is obtained from measurements of brain tissue oxygen tension (PbtO2) and biochemical data obtained from intracerebral microdialysis. As interstitial lactate/pyruvate (LP) ratio instantaneously reflects shifts in intracellular cytoplasmatic redox state, it is an important indicator of compromised cerebral oxidative metabolism. The combined information obtained from PbtO2, LP ratio, and the pattern of biochemical variables reveals whether impaired oxidative metabolism is due to insufficient perfusion (ischemia) or mitochondrial dysfunction. Intracerebral microdialysis and PbtO2 give information from a very small volume of tissue. Accordingly, clinical interpretation of the data must be based on information of the probe location in relation to focal brain damage. Attempts to evaluate global cerebral energy state from microdialysis of intraventricular fluid and from the LP ratio of the draining venous blood have recently been presented. To be of clinical relevance, the information from all monitoring techniques should be presented bedside online. Accordingly, in the future, the chemical variables obtained from microdialysis will probably be analyzed by biochemical sensors.

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Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

Cited by 47 publications

References 125 publications

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

Decline of Lactate in Tumor Tissue After Ketogenic Diet: In Vivo Microdialysis Study in Patients with Head and Neck Cancer

Aspects on the Physiological and Biochemical Foundations of Neurocritical Care

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