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01-12-2011 | Review Article

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

Authors: Daniel B. Larach, W. Andrew Kofke, Peter Le Roux

Published in: Neurocritical Care | Issue 3/2011

Abstract

Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.

Ungerstedt U, Pycock C. Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss. 1974;30:44–55.PubMed

Chefer VI, Thompson AC, Zapata A, Shippenberg TS. Overview of brain microdialysis. Curr Protoc Neurosci. 2009;47:7.1.1–1.28.

Torregrossa MM, Kalivas PW. Microdialysis and the neurochemistry of addiction. Pharmacol Biochem Behav. 2008;90:261–72.PubMedCrossRef

Meeusen R. Exercise and the brain: insight in new therapeutic modalities. Ann Transplant. 2005;10:49–51.PubMed

van der Zeyden M, Oldenziel WH, Rea K, Cremers TI, Westerink BH. Microdialysis of GABA and glutamate: analysis, interpretation and comparison with microsensors. Pharmacol Biochem Behav. 2008;90:135–47.PubMedCrossRef

Li Y, Peris J, Zhong L, Derendorf H. Microdialysis as a tool in local pharmacodynamics. AAPS J. 2006;8:E222–35.PubMed

Stiller CO, Taylor BK, Linderoth B, Gustafsson H, Warsame Afrah A, Brodin E. Microdialysis in pain research. Adv Drug Deliv Rev. 2003;55:1065–79.PubMedCrossRef

Meyerson BA, Linderoth B, Karlsson H, Ungerstedt U. Extracellular measurements in the thalamus of parkinsonian patients. Life Sci. 1990;46:301–8.PubMedCrossRef

Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22:3–41.PubMedCrossRef

10.

Bellander BM, Cantais E, Enblad P, et al. Consensus meeting on microdialysis in neurointensive care. Intensive Care Med. 2004;30:2166–9.PubMedCrossRef

11.

Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M. Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study. Acta Neurochir (Wien). 2008;150:461–9.CrossRef

12.

Adamides AA, Rosenfeldt FL, Winter CD, et al. Brain tissue lactate elevations predict episodes of intracranial hypertension in patients with traumatic brain injury. J Am Coll Surg. 2009;209:531–9.PubMedCrossRef

13.

Ungerstedt U, Rostami E. Microdialysis in neurointensive care. Curr Pharm Des. 2004;10:2145–52.PubMedCrossRef

14.

Goodman JC, Robertson CS. Microdialysis: is it ready for prime time? Curr Opin Crit Care. 2009;15:110–7.PubMedCrossRef

15.

Nordström CH. Cerebral energy metabolism and microdialysis in neurocritical care. Childs Nerv Syst. 2010;26:465–72.PubMedCrossRef

16.

Tisdall MM, Smith M. Cerebral microdialysis: research technique or clinical tool. Br J Anaesth. 2006;97:18–25.PubMedCrossRef

17.

Oddo M, Schmidt JM, Carrera E, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med. 2008;36:3233–8.PubMedCrossRef

18.

Vespa PM, McArthur D, O’Phelan K, et al. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab. 2003;23:865–77.PubMedCrossRef

19.

Oddo M, Milby A, Chen I, et al. Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2009;40:1275–81.PubMedCrossRef

20.

Nordström CH, Reinstrup P, Xu W, Gärdenfors A, Ungerstedt U. Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology. 2003;98:809–14.PubMedCrossRef

21.

Vespa PM, Miller C, McArthur D, et al. Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Crit Care Med. 2007;35:2830–6.PubMedCrossRef

22.

Hashemi P, Bhatia R, Nakamura H, et al. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leão’s spreading depression. J Cereb Blood Flow Metab. 2009;29:166–75.PubMedCrossRef

23.

Schneweis S, Grond M, Staub F, et al. Predictive value of neurochemical monitoring in large middle cerebral artery infarction. Stroke. 2001;32:1863–7.PubMedCrossRef

24.

Nortje J, Coles JP, Timofeev I, et al. Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic brain injury: preliminary findings. Crit Care Med. 2008;36:273–81.PubMedCrossRef

25.

Marcoux J, McArthur DA, Miller C, et al. Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Crit Care Med. 2008;36:2871–7.PubMedCrossRef

26.

Hillered L, Persson L, Nilsson P, Ronne-Engstrom E, Enblad P. Continuous monitoring of cerebral metabolism in traumatic brain injury: a focus on cerebral microdialysis. Curr Opin Crit Care. 2006;12:112–8.PubMedCrossRef

27.

Leegsma-Vogt G, van der Werf S, Venema K, Korf J. Modeling cerebral arteriovenous lactate kinetics after intravenous lactate infusion in the rat. J Cereb Blood Flow Metab. 2004;24:1071–80.PubMedCrossRef

28.

Miller LP, Oldendorf WH. Regional kinetic constants for blood-brain barrier pyruvic acid transport in conscious rats by the monocarboxylic acid carrier. J Neurochem. 1986;46:1412–6.PubMedCrossRef

29.

Hutchinson PJ, O’Connell MT, Al-Rawi PG, et al. Clinical cerebral microdialysis: a methodological study. J Neurosurg. 2000;93:37–43.PubMedCrossRef

30.

Nelson DL, Cox MM. Lehninger principles of biochemistry. 5th ed. New York: WH Freeman; 2008.

31.

Johnston AJ, Gupta AK. Advanced monitoring in the neurology intensive care unit: microdialysis. Curr Opin Crit Care. 2002;8:121–7.PubMedCrossRef

32.

Reinstrup P, Ståhl N, Mellergård P, Uski T, Ungerstedt U, Nordström CH. Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery. Neurosurgery. 2000;47:701–9.PubMed

33.

Gårdenfors A, Nilsson F, Skagerberg G, Ungerstedt U, Nordström CH. Cerebral physiological and biochemical changes during vasogenic brain edema induced by intrathecal injection of bacterial lipopolysaccharides in piglets. Acta Neurochir. 2002;144:601–8.CrossRef

34.

Dusick JR, Glenn TC, Lee WN, et al. Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1, 2–13C2]glucose labeling study in humans. J Cereb Blood Flow Metab. 2007;27:1593–602.PubMedCrossRef

35.

Vespa P, Bergsneider M, Hattori N, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25:763–4.PubMedCrossRef

36.

Simpson NE, Han Z, Berendzen KM, et al. Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: effects of pyruvate dehydrogenase complex deficiency and dichloroacetate. Mol Genet Metab. 2006;89:97–105.PubMedCrossRef

37.

Nakasaki H, Ohta M, Soeda J, et al. Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition. Nutrition. 1997;13:110–7.PubMedCrossRef

38.

Tinsa F, Ben Amor S, Kaabachi N, Ben Lasouad M, Boussetta K, Bousnina S. Unusual case of thiamine responsive megaloblastic anemia. Tunis Med. 2009;87:159–63.PubMed

39.

Poggi-Travert F, Martin D, Billette de Villemeur T, et al. Metabolic intermediates in lactic acidosis: compounds, samples and interpretation. J Inherit Metab Dis. 1996;19:478–88.PubMedCrossRef

40.

Stacpoole PW, Wright EC, Baumgartner TG, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. NEJM. 1992;327:1564–9.PubMedCrossRef

41.

Hoppel CL, Kerr DS, Dahms B, Roessmann U. Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. J Clin Invest. 1987;80:71–7.PubMedCrossRef

42.

Moreadith RW, Batshaw ML, Ohnishi T, et al. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis. J Clin Invest. 1984;74:685–97.PubMedCrossRef

43.

Robinson BH, McKay N, Goodyer P, Lancaster G. Defective intramitochondrial NADH oxidation in skin fibroblasts from an infant with fatal neonatal lacitcacidemia. Am J Hum Genet. 1985;37:938–46.PubMed

44.

Van Hove JL, Saenz MS, Thomas JA, et al. Succinyl-CoA ligase deficiency: a mitochondrial hepatoencephalomyopathy. Pediatr Res. 2010;68:159–64.PubMedCrossRef

45.

Chesney RW, Kaplan BS, Colle E, et al. Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. Pediatr Res. 1980;14:209–15.PubMed

46.

Boustany RN, Aprille JR, Halperin J, Levy H, DeLong GR. Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin. Ann Neurol. 1983;14:462–70.PubMedCrossRef

47.

Komaki H, Nishigaki Y, Fuku N, et al. Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency. Biochim Biophys Acta. 2010;1800:313–5.PubMedCrossRef

48.

Mannan AA, Sharma MC, Shrivastava P, et al. Leigh’s syndrome. Indian J Pediatr. 2004;71:1029–33.PubMedCrossRef

49.

Hertz L, Kala G. Energy metabolism in brain cells: effects of elevated ammonia concentrations. Metab Brain Dis. 2007;22:199–218.PubMedCrossRef

50.

Lin S, Raabe W. Ammonia intoxication: effects on cerebral cortex and spinal cord. J Neurochem. 1985;44:1252–8.PubMedCrossRef

51.

Adams JM, Feustel PJ, Donnelly DF, Dutton RE. Hypoxia, hyperammonemia, and cerebrospinal fluid metabolites. Adv Shock Res. 1978;1:209–20.PubMed

52.

O’Connor JE, Costell M, Grisolía S. Prevention of ammonia toxicity by L-carnitine: metabolic changes in brain. Neurochem Res. 1984;9:563–70.PubMedCrossRef

53.

Hindfelt B, Plum F, Duffy TE. Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest. 1977;59:386–96.PubMedCrossRef

54.

Bjerring PN, Hauerberg J, Frederiksen HJ, et al. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure. Neurocrit Care. 2008;9:3–7.PubMedCrossRef

55.

Ratnakumari L, Murthy CR. Response of rat cerebral glycolytic enzymes to hyperammonemic states. Neurosci Lett. 1993;161:37–40.PubMedCrossRef

56.

Qureshi K, Rama Rao KV, Qureshi IA. Differential inhibition by hyperammonemia of the electron transport chain enzymes in synaptosomes and non-synaptic mitochondria in ornithine transcarbamylase-deficient spf-mice: restoration by acetyl-L-carnitine. Neurochem Res. 1998;23:855–61.PubMedCrossRef

57.

Ratnakumari L, Qureshi IA, Butterworth RF. Effects of congenital hyperammonemia on the cerebral and hepatic levels of the intermediates of energy metabolism in spf mice. Biochem Biophys Res Commun. 1992;184:746–51.PubMedCrossRef

58.

She P, Zhou Y, Zhang Z, Griffin K, Gowda K, Lynch CJ. Disruption of BCAA metabolism in mice impairs exercise metabolism and endurance. J Appl Physiol. 2010;108:941–9.PubMedCrossRef

59.

Kauppinen RA, Sihra TS, Nicholls DG. Aminooxyacetic acid inhibits the malate-aspartate shuttle in isolated nerve terminals and prevents the mitochondria from utilizing glycolytic substrates. Biochim Biophys Acta. 1987;930:173–8.PubMedCrossRef

60.

Nagasaka H, Okano Y, Tsukahara H, et al. Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period. Mol Genet Metab. 2009;97:21–6.PubMedCrossRef

61.

Hanley PJ, Ray J, Brandt U, Daut J. Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol. 2002;544:687–93.PubMedCrossRef

62.

Michenfelder JD, Theye RA. In vivo toxic effects of halothane on canine cerebral metabolic pathways. Am J Physiol. 1975;229:1050–5.PubMed

63.

Dahlbacka S, Mäkelä J, Kaakinen T, et al. Propofol is associated with impaired brain metabolism during hypothermic circulatory arrest: an experimental microdialysis study. Heart Surg Forum. 2006;9:E710–8.PubMedCrossRef

64.

Carles M, Dellamonica J, Roux J, et al. Sevoflurane but not propofol increases interstitial glycolysis metabolites availability during tourniquet-induced ischaemia-reperfusion. Br J Anaesth. 2008;100:29–35.PubMedCrossRef

65.

Marian M, Parrino C, Leo AM, Vincenti E, Bindoli A, Scutari G. Effect of the intravenous anesthetic 2,6-diisopropylphenol on respiration and energy production by rat brain synaptosomes. Neurochem Res. 1997;22:287–92.PubMedCrossRef

66.

Branca D, Roberti MS, Lorenzin P, Vincenti E, Scutari G. Influence of the anesthetic 2,6-diisopropylphenol on the oxidative phosphorylation of isolated rat liver mitochondria. Biochem Pharmacol. 1991;42:87–90.PubMedCrossRef

67.

Fudickar A, Bein B. Propofol infusion syndrome: update of clinical manifestation and pathophysiology. Minerva Anestesiol. 2009;75:339–44.PubMed

68.

Pisapia JM, Wendell LC, Kumar MA, Zager EL, Levine JM. Lactate-to-pyruvate ratio as a marker of propofol infusion syndrome after subarachnoid hemorrhage. Neurocrit Care. 2010. doi:10.1007/s12028-010-9467-6.

69.

Nam YT, Kim JS, Park KW. Effects of hypotensive anesthesia with sodium nitroprusside or isoflurane on hemodynamic and metabolic changes. Yonsei Med J. 1992;33:320–5.PubMed

70.

Michenfelder JD. Cyanide release from sodium nitroprusside in the dog. Anesthesiology. 1977;46:196–201.PubMedCrossRef

71.

Tinker JH, Michenfelder JD. Cardiac cyanide toxicity induced by nitroprusside in the dog: potential for reversal. Anesthesiology. 1978;49:109–16.PubMedCrossRef

72.

Dai YL, Luk TH, Siu CW, et al. Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease. Cardiovasc Toxicol. 2010;10:130–8.PubMedCrossRef

73.

Ruddick JA. Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol Appl Pharmacol. 1972;21:102–11.PubMedCrossRef

74.

Saini M, Nagpaul JP, Amma MK. Effect of propane-1,2-diol ingestion on carbohydrate metabolism in female rat erythrocytes. J Appl Toxicol. 1993;13:69–75.PubMedCrossRef

75.

Morshed KM, Nagpaul JP, Majumdar S, Amma MKP. Kinetics of oral propylene glycol-induced acute hyperlactatemia. Biochem Med Metab Biol. 1989;42:87–94.PubMedCrossRef

76.

Schölmerich J, Kitamura S, Miyai K. Effects of propylene glycol on redox state of the perfused rat liver—a note of caution. Res Exp Med (Berl). 1989;189:39–42.CrossRef

77.

Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines. Chest. 2005;128:1674–81.PubMedCrossRef

78.

Barnes BJ, Gerst C, Smith JR, Terrell AR, Mullins ME. Osmol gap as a surrogate marker for serum propylene glycol concentrations in patients receiving lorazepam for sedation. Pharmacotherapy. 2006;26:23–33.PubMedCrossRef

79.

Ganesh A, Audu P. Hyperosmolar, increased-anion-gap metabolic acidosis and hyperglycemia after etomidate infusion. J Clin Anesth. 2008;20:290–3.PubMedCrossRef

80.

Szajewski J. Poisons information monographs: Propylene glycol. No. 443. Geneva, Switzerland: International Programme on Chemical Safety, 1994.

81.

Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Sem Dial. 2007;20:217–9.CrossRef

82.

Rengel-Aranda M, Gougoux A, Vinay P, Lopez-Novoa JM. Effect of valproate on renal metabolism in the intact dog. Kidney Int. 1988;34:645–54.PubMedCrossRef

83.

Dubas TC, Johnson WJ. Metformin-induced lactic acidosis: potentiation by ethanol. Res Commun Chem Pathol Pharmacol. 1981;33:21–31.PubMed

84.

Jalling O, Olsen C. The effects of metformin compared to the effects of phenformin on the lactate production and the metabolism of isolated parenchymal rat liver cell. Acta Pharmacol Toxicol (Copenh). 1984;54:327–32.CrossRef

85.

Nattrass M, Hinks L, Smythe P, Todd PG, Alberti KGMM. Metabolic effects of combined sulphonylurea and metformin therapy in maturity-onset diabetes. Horm Metab Res. 1979;11:332–7.PubMedCrossRef

86.

Ramanathan S, Masih AK, Ashok U, Arismendy J, Turndorf H. Concentrations of lactate and pyruvate in maternal and neonatal blood with different intravenous fluids used for prehydration before epidural anesthesia. Anesth Analg. 1984;63:69–74.PubMedCrossRef

87.

Pellerin L, Bouzier-Sore AK, Aubert A, et al. Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia. 2007;55:1251–62.PubMedCrossRef

88.

Brown AM, Ransom BR. Astrocyte glycogen and brain energy metabolism. Glia. 2007;55:1263–71.PubMedCrossRef

89.

Bittar PG, Charnay Y, Pellerin L, Bouras C, Magistretti PJ. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab. 1996;16:1079–89.PubMedCrossRef

90.

Abi-Saab WM, Maggs DG, Jones T, et al. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab. 2002;22:271–9.PubMedCrossRef

91.

Agardh CD, Folbergrová J, Siesjö BK. Cerebral metabolic changes in profound, insulin-induced hypoglycemia, and in the recovery period following glucose administration. J Neurochem. 1978;31:1135–42.PubMedCrossRef

92.

Cardell M, Siesjö BK, Wieloch T. Changes in pyruvate dehydrogenase complex activity during and following severe insulin-induced hypoglycemia. J Cereb Blood Flow Metab. 1991;11:122–8.PubMedCrossRef

93.

Schlenk F, Nagel A, Graetz D, Sarrafzadeh AS. Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage. Intensive Care Med. 2008;34:1200–7.PubMedCrossRef

94.

Vespa P, Boonyaputthikul R, McArthur DL, et al. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med. 2006;34:850–6.PubMedCrossRef

95.

Kennan RP, Takahashi K, Pan C, Shamoon H, Pan JW. Human cerebral blood flow and metabolism in acute insulin-induced hypoglycemia. J Cereb Blood Flow Metab. 2005;25:527–34.PubMedCrossRef

96.

Choi IY, Lee SP, Kim SG, Gruetter R. In vivo measurements of brain glucose transport using the reversible Michaelis-Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia. J Cereb Blood Flow Metab. 2001;21:653–63.PubMedCrossRef

97.

Eckert B, Ryding E, Agardh CD. Sustained elevation of cerebral blood flow after hypoglycaemia in normal man. Diabetes Res Clin Pract. 1998;40:91–100.PubMedCrossRef

98.

Rosdahl H, Samuelsson AC, Ungerstedt U, Henriksson J. Influence of adrenergic agonists on the release of amino acids from rat skeletal muscle studied by microdialysis. Acta Physiol Scand. 1998;163:349–60.PubMedCrossRef

99.

Levy B, Mansart A, Bollaert PE, Franck P, Mallie JP. Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats. Intensive Care Med. 2003;29:292–300.PubMed

100.

Levy B, Bollaert PE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med. 1997;23:282–7.PubMedCrossRef

101.

Pernet A, Walker M, Gill GV, Ørskov H, Alberti KGMM, Johnston DG. Metabolic effects of adrenaline and noradrenaline in man: studies with somatostatin. Diabete Metab. 1984;10:98–105.PubMed

102.

Christensen NJ, Alberti KG, Brandsborg O. Plasma catecholamines and blood substrate concentrations: studies in insulin induced hypoglycaemia and after adrenaline infusions. Eur J Clin Invest. 1975;5:415–23.PubMed

103.

Heringlake M, Wernerus M, Grünefeld J, et al. The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting. Crit Care. 2007;11:R51.PubMedCrossRef

104.

Cano A, Martínez P, Parrilla JJ, Abad L. Effects of intravenous ritodrine on lactate and pyruvate levels: role of glycemia and anaerobiosis. Obstet Gynecol. 1985;66:207–10.PubMed

105.

d’Avila JC, Santiago AP, Amâncio RT, et al. Sepsis induces brain mitochondrial dysfunction. Crit Care Med. 2008;36:1925–32.PubMedCrossRef

106.

Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H. Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol. 1986;250:E634–40.PubMed

107.

Malaisse WJ, Nadi AB, Ladriere L, Zhang TM. Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia. Nutrition. 1997;13:330–41.PubMed

108.

Gnaegi A, Feihl F, Boulat O, Waeber B, Liaudet L. Moderate hypercapnia exerts beneficial effects on splanchnic energy metabolism during endotoxemia. Intensive Care Med. 2009;35:1297–304.PubMedCrossRef

109.

Chvojka J, Sykora R, Krouzecky A, et al. Renal haemodynamic, microcirculatory, metabolic and histopathological responses to peritonitis-induced septic shock in pigs. Crit Care. 2008;12:R164.PubMedCrossRef

110.

Boekstegers P, Weidenhöfer S, Kapsner T, Werdan K. Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med. 1994;22:640–50.PubMedCrossRef

111.

Astiz M, Rackow EC, Weil MH, Schumer W. Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock. 1988;26:311–20.PubMed

112.

Blennow G, Folbergrová J, Nilsson B, Siesjö BK. Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine. Brain Res. 1979;179:129–46.PubMedCrossRef

113.

Folbergrová J, Jesina P, Drahota Z, et al. Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures. Exp Neurol. 2007;204:597–609.PubMedCrossRef

114.

Howse DCN. Metabolic responses to status epilepticus in the rat, cat, and mouse. Can J Physiol Pharmacol. 1979;57:205–12.PubMedCrossRef

115.

Folbergrová J, Ingvar M, Nevander G, Siesjö BK. Cerebral metabolic changes during and following fluorothyl-induced seizures in ventilated rats. J Neurochem. 1985;44:1419–26.PubMedCrossRef

116.

Ingvar M, Folbergrová J, Siesjö BK. Metabolic alterations underlying the development of hypermetabolic necrosis in the substantia nigra in status epilepticus. J Cereb Blood Flow Metab. 1987;7:103–8.PubMedCrossRef

117.

Chapman AG, Meldrum BS, Siesjö BK. Cerebral metabolic changes during prolonged epileptic seizures in rats. J Neurochem. 1977;28:1025–35.PubMedCrossRef

118.

Johansson BB, Fredriksson K. Cerebral energy metabolism during bicuculline-induced status epilepticus in spontaneously hypertensive rats. Acta Phys Scand. 1985;123:299–302.CrossRef

119.

Slais K, Vorisek I, Zoremba N, Homola A, Dmytrenko L, Sykova E. Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus. Exp Neurol. 2008;209:145–54.PubMedCrossRef

120.

Darbin O, Risso JJ, Carre E, Lonjon M, Naritoku DK. Metabolic changes in rat striatum following convulsive seizures. Brain Res. 2005;1050:124–9.PubMedCrossRef

121.

Claassen J, Jetté N, Chum F, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007;69:1256–65.CrossRef

122.

Folbergrová J, MacMillan V, Siesjö BK. The effect of moderate and marked hypercapnia upon the energy state and upon the cytoplasmic NADH-NAD+ ratio of the rat brain. J Neurochem. 1972;19:2497–505.PubMedCrossRef

123.

Folbergrová J, Pontén U, Siesjö BK. Patterns of changes in brain carbohydrate metabolites, amino acids and organic phosphates at increased carbon dioxide tensions. J Neurochem. 1974;22:1115–25.PubMedCrossRef

124.

Weyne J, Demeester G, Leusen I. Effects of carbon dioxide, bicarbonate, and pH on lactate and pyruvate in the brain of rats. Pflugers Arch. 1970;31:292–311.CrossRef

125.

Kjällquist Å, Nardini M, Siesjö BK. The regulation of extra- and intracellular acid-base parameters in the rat brain during hyper- and hypocapnia. Acta Physiol Scand. 1969;76:485–94.PubMedCrossRef

126.

Granholm L, Siesjö BK. The effects of hypercapnia and hypocapnia upon the cerebrospinal fluid lactate and pyruvate concentrations and upon the lactate, pyruvate, ATP, ADP, phosphocreatine and creatine concentrations of cat brain tissue. Acta Physiol Scand. 1969;75:257–66.PubMedCrossRef

127.

Frauendorf E, Hartmann N, Hübner G, Meng W, Weber A. Das verhalten des laktat/pyruvat-quotienten im rahmen moderner schilddrüsendiagnostik. Z Gesamte Inn Med. 1980;35:155–61.PubMed

128.

Hübner G, Schwinger E, Meng W. Zum verhalten von laktat und pyruvat sowie des laktat/pyruvat-quotienten im blut bei schilddrüsenfunktionsstörungen des menschen. Z Gesamte Inn Med. 1975;30:786–9.PubMed

129.

Katyare SS, Joshi MV, Fatterpaker P, Sreenivasan A. Effect of thyroid deficiency on oxidative phosphorylation in rat liver, kidney, and brain mitochondria. Arch Biochem Biophys. 1977;182:155–63.PubMedCrossRef

130.

Lecky FE, Little RA, Maycock PF, et al. Effect of alcohol on the lactate/pyruvate ratio of recently injured adults. Crit Care Med. 2002;30:981–5.PubMedCrossRef

131.

Yap M, Mascord DJ, Starmer GA, Whitfield JB. Studies on the chronopharmacology of ethanol. Alcohol Alcohol. 1993;28:17–24.PubMed

132.

Myrsten AL, Rydberg U, Ideström CM, Lamble R. Alcohol intoxication and hangover: modification of hangover by chlormethiazole. Psychopharmacology (Berl). 1980;69:117–25.CrossRef

133.

Ginestal da Cruz A, Correia JP, Menezes L. Ethanol metabolism in liver cirrhosis and chronic alcoholism. Acta Hepatogastroenterol (Stuttg). 1975;22:369–74.

134.

Frayn KN, Coppack SW, Walsh PE, Butterworth HC, Humphreys SM, Pedrosa HC. Metabolic responses of forearm and adipose tissues to acute ethanol ingestion. Metabolism. 1990;39:958–66.PubMedCrossRef

135.

Hollstedt C, Rydberg U, Olsson O, Buijten J. Effects of ethanol on the developing rat. I. Ethanol metabolism and effects on lactate, pyruvate, and glucose concentrations. Med Biol. 1980;58:158–63.PubMed

136.

Pronko PS, Velichko MG, Moroz AR, Rubanovich NN. Low-molecular-weight metabolites relevant to ethanol metabolism: correlation with alcohol withdrawal severity and utility for identification of alcoholics. Alcohol Alcohol. 1997;32:761–8.PubMed

137.

Krebs HA, Freedland RA, Hems R, Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J. 1969;112:117–24.PubMed

138.

Tskuamoto S, Kanegae T, Saito M, et al. Concentrations of blood and urine ethanol, acetaldehyde, acetate and acetone during experimental hangover in volunteers. Arukoru Kenkyuto Yakubutsu Ison. 1991;26:500–10.

139.

Martin E, Rosenthal RE, Fiskum G. Pyruvate dehydrogenase complex: metabolic link to ischemic brain injury and target of oxidative stress. J Neurosci Res. 2005;79:240–7.PubMedCrossRef

140.

Ehrig K, Heckel R, Lajios G. Molecular analysis of metabolic pathway with graph transformation. Lect Notes Comput Sci. 2006;4178:107–21.CrossRef

Title: Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature
Authors: Daniel B. Larach
W. Andrew Kofke
Peter Le Roux
Publication date: 01-12-2011
Publisher: Humana Press Inc
Published in: Neurocritical Care / Issue 3/2011
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-011-9517-8

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

Abstract

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Abstract

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