Abstract
A central research problem in pharmacology has been identification of the mechanism(s) and site(s) of action of general anaesthetics within the central nervous system. Ideally, a method to investigate the effects of general anaesthetics should provide information on the functional changes occurring in neuronal cells during the anaesthetic state. Electrical activity of the primary neuronal function can not be easily mapped but drives neuronal metabolic activities. Specifically, under normal conditions glucose is almost the exclusive substrate for neuronal energetic requirements and is a major factor that regulates cerebral blood flow; hence, determination of regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF) provide two surrogate measures of neuronal functional activities. In the late 1970s were introduced the [14C] 2-deoxy-d-glucose [1] and [14C] iodoantipyrine [2] autoradiographic techniques for the measurement of rCMRglc and rCBF in animals. Deoxyglucose is an analogue of glucose that is taken up at a fixed ratio with glucose, trapped into the neuronal cells, and not further metabolized [1]; antipyrine is a highly diffusible molecule that freely crosses the bloodbrain barrier and distributes according to blood flow [2]. Brain concentrations of both [14C] 2-deoxy-D-glucose and [14C] iodoantipyrine are hence markers of rCMRglc and rCBF and can then be determined autoradiographically.
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References
Sokoloff L, Reivich M, Kennedy C, et al (1977) The [14CJdeoxyglucose method for the measurement of local cerebral glucose utilization. Theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916
Sakurada O, Kennedy C, Jehle J, et al (1978) Measurements of local cerebral blood flow with iodo[i^C]antipyrine. Am J Physiol 234:H59-H66
Aine JC (1995) A conceptual overview and critique of functional neuroimaging techniques in humans: 1. MRI/fMRI and PET. Crit Rev Neurobiol 9:229–309
Herscovitcb P, Markham J, Raichle ME (1983) Brain blood flow measured with intravenous ffisO. I. Theory and error analysis. J Nucl Med 24:782–789
Ogawa S, Lee TM, Kay AR, et al (1990) Brain magnetic resonance imaging with contrast dependent on blood oxigenation. Proc Natl Acad Sci U S A 87:9868–9872
Myers RR, Shapiro HM (1979) Local cerebral metabohsm during enflurane anesthesia: identification of epileptogenic foci. Electroencephal Clin Neurophysiol 47:153–162
Nakakimura K, Sakabe T, Funatsu N, et al (1988) Metabolic activation of intercortical and corticothalamic pathways during enflurane anesthesia in rats. Anesthesiology 68:777–782
Crosby G, Atlas S (1988) Local spinal cord glucose utilization in conscious and halothane- -anesthetized rats. Can J Anaesth 35:359–363
Savaki HE, Desban M, Glowinski J, et al (1983) Local cerebral glucose consumption in the rat. 1. Effects of halothane anesthesia. J Comp Neurol 213:36–45
Ori C, Dam M, Pizzolato G, et al (1986) Effects of isoflurane anesthesia on local cerebral glucose metabolism in the rat. Anesthesiology 65:152–156
Lenz C, Rebel A, Ackem K van, et al (1998) Local cerebral blood flow, local cerebral glucose utilization, and flow-metaboUsm coupling during sevoflurane versus isoflurane anesthesia in rats. Anesthesiology 89:1480–1488
Maekawa T, Tommasino C, Shapiro HM, et al (1986) Local cerebral blood flow and glucose utilization during isoflurane anesthesia in the rat. Anesthesiology 65:144–151
Hendrich KS, Kochaneck PM, Melick JA, et al (2001) Cerebral perfusion during anesthesia with fentanyl, isoflurane, or pentobarbital in normal rats studied with arterial spin-labeled MRI. Magn Reson Med 46:202–206
Hansen TD, Warner DS, Todd MM, et al (1989) The role of cerebral metabohsm in determining the local cerebral blood flow effects of volatile anesthetics: evidence for persisting flow-meta- bohsm coupling. J Cereb Blood Flow Metab 9:323–328
Shapiro HM, Greenberg JH, Reivich M, et al (1978) Local cerebral glucose uptake in awake and halothane-anesthetized primates. Anesthesiology 48:97–103
Alkire MT, Haier RJ, Shah NK, et al (1997) Positron emission tomography study of regional cerebral metabolism in humans during isoflurane anesthesia. Anesthesiology 86:549–557
Alkire MT (1998) Quantitative EEG correlations with brain glucose metabolic rate during anesthesia in volunteers. Anesthesiology 89:323–333
Alkire MT, Pomfrett CJD, Haier RJ, et al (1999) Functional brain imaging during anesthesia in humans. Effects of halothane on global and regional cerebral glucose metabohsm. Anesthesiology 90:701–709
Alkire MT, Haier RJ, Fallon JH (2000) Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness. Conscious Cogn 9:370–386
Kaisti KK, Metsahonkala L, Teras M, et al (2002) Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiology 96:1358–1370
Kaisti KK, Jaaskelainen SK, Rinne JO, et al (1999) Epileptiform discharges during 2 MAC sevoflurane anesthesia in two healthy volunteers. Anesthesiology 91:1952–1955
Antognini JF, Buonocore MH, Disbrow EA, et al (1997) Isoflurane anesthesia blunts cerebral responses to noxious and innocuous stimuli: a fMRI study. Life Sci 61:349–354
Heinke W, Schwarzbauer C (2001) Subanesthetic isoflurane affects task-induced brain activation in a highly specific manner. Anesthesiology 94:973–981
London E, Fanelli R, Szikszay M, et al (1986) Effects of opioid analgesics on local cerebral glucose utilization. NIDA Res Monograr 75:379–381
Cohen SR, Kimes AS, London ED (1991) Morphine decreases cerebral glucose utilization in limbic and forebrain regions while pain has no effect. Neuropharmacology 30:125–134
Beck T, Kriegelstein J (1986) The effects of tifluadom and ketazocine on behavior, dopamine turnover in the basal ganglia and local cerebral glucose utilization in rats. Brain Res 381:327–335
Orzi F, Passarel H F, La Riccia M, et al (1996) Intravenous morphine increases glucose utilization in the shell of the rat nucleus accumbens. Eur J Pharmacol 302:49–51
Tommasino C, Maekawa T, Shapiro HM, et al (1984) Fentanyl-induced seizures activate subcortical brain metabohsm. Anesthesiology 60:283–290
Kofke WA, Garman RH, Tom WC, et al (1992) Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain. Anesth Analg 75:953–964
Kofke WA, Attaallah AF, Kuwabara H, et al (2002) The neuropathologic effects in rats and neurometabohc effects in humans of large-dose remifentanil. Anesth Analg 94:1229–1236
Young ML, Smith DS, Greenberg J, et al (1984) Effects of sufentanil on regional cerebral glucose utilization in rats. Anesthesiology 61:564–568
Beck T, Wenzel J, Kuschinsky K, et al (1989) Morphine-induced alterations of local cerebral glucose utilization in the basal gangha of rats. Brain Res 497:205–213
Ableitner A (1994) Brain sites involved in delta-opioid receptor-mediated actions. Eur J Pharmacol 271:213–222
Kraus MA, Piper JM, Kometsky C (1996) Naloxone alters the local metabolic rate for glucose in discrete bram regions associated with opiate withdrawal. Brain Res 724:33–40
Levy RM, Fields HL, Stryker MP, et al (1986) The effect of analgesic doses of morphine on regional cerebral glucose metabohsm in pain-related structures. Brain Res 368:170–173
Gescuk B, Lang S, Porrino LJ, et al (1994) The local cerebral metabohc effects of morphine in rats exposed to escapable footshock. Brain Res 663:303–311
Tuor UI, Mahsza K, Foniok T, et al (2000) Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw. Pain 87:315–324
Chang C, Shyu BC (2001) A fMRI study of brain activations during non-noxious and noxious electrical stimulation of the sciatic nerve of rats. Brain Res 897:71–81
Jones AK, Friston KJ, Qi LY, et al (1991) Sites of action of morphine in the brain (letter). Lancet 338:825
London ED, Broussolle EP, Links JM, et al (1990) Morphine-induced metabohc changes in human brain. Studies with positron emission tomography and [18F]flurodoxyglucose. Arch Gen Psychiatry 47:73–81
Walsh SL, Gilson SF, Jasinski DR, et al (1994) Buprenorphine reduces cerebral glucose metabohsm in poly drug abusers. Neuropsychopharmacology 10:157–170
Schlaepfer TE, Strain EC, Greenberg BD, et al (1998) Site of opioid action in the human brain: mu and kappa agonists’ subjective and cerebral blood flow effects. Am J Psychiatry 155:470–473
Firestone LL, Gyulai F, Mintun M, et al (1996) Human brain activity response to fentanyl imaged by positron emission tomography Anesth Analg 82:1247–1251
Wagner KJ, Willoch F, Kochs EF, et al (2001) Dose-dependent regional cerebral blood flow changes during remifentanil infusion in humans. Anesthesiology 94:732–739
Lorenz IH, Kolbitsch C, Schocke M, et al (2000) Low-dose remifentanil increases regional cerebral blood flow and regional cerebral blood volume, but decreases regional mean transit time and regional cerebrovascular resistance in volunteers. Br J Anaesth 85:199–204
Duncan GH, Bushnell MC, Friston KJ, et al (1992) Pain and activation in the thalamus. Trends Neurosci 15:1355
Adler LJ, Gyulai EE, Diehl DJ, et al (1997) Regional brain activity changes associated with fentanyl analgesia elucidated by positron emission tomography Anesth Analg 84:120–126
Cole DJ, Shapiro HM (1989) Different 1.2 MAC combinations of nitrous oxide-enflurane cause unique cerebral and spinal cord metabolic responses in the rat. Anesthesiology 70:787–792
Crosby G, Crane AM, Sokoloff L (1984) A comparison of local rates of glucose utilization in spinal cord and brain in conscious and nitrous oxide or pentobarbital-treated rats. Anesthesiology 61:434–438
Sakabe T, Tsutsui T, Maekawa T, et al (1985) Local cerebral glucose utilization during nitrous oxide and pentobarbital anesthesia in rats. Anesthesiology 63:262–266
Crosby G, Crane AM, Jehle J, et al (1983) The local metabohc effects of somatosensory stimulation in the central nervous system of rats given pentobarbital or nitrous oxide. Anesthesiology 58:38–43
Gyulai EE, Firestone LL, Mintun MA, et al (1996) In vivo imaging of human limbic responses to noxious stimuli. Anesth Analg 83:291–298
Gyulai EE, Firestone LL, Mintun MA (1997) In vivo imaging of nitrous oxide-induced changes in cerebral activation during noxious heat stimuli. Anesthesiology 86:538–548.
Ori C, Freo U, Perini G, Dam M (1995) Dissociated behavioral and regional cerebral metabolic (rCMRglc) effects of midazolam and flunitrazepam in rats. XXV Meeting of the Society for Neuroscience Abstract Book 21:157
Veselis RA, Reinsel RA, Beattie BJ, et al (1997) Midazolam changes cerebral blood flow in discrete brain regions: an H2(15)0 positron emission tomography study. Anesthesiology 87: 1106–1117
Mathew RJ, Wilson WH, Daniel DG (1985) The effect of nonsedating doses of diazepam on regional cerebral blood flow. Biol Psychiatiy 20:1109–1116
Volkow ND, Wang GJ, Hitzemann R, et al (1995) Depression of thalamic metabohsm by lorazepam is associated with sleepiness. Neuropsychopharmacology 12:123–132
Hodes JE, Soncrant TT, Larson DM, et al (1985) Selective changes in local cerebral glucose utilization by phénobarbital in the rat. Anesthesiology 63:633–639
Herkenham M (1981) Anesthetics and the habenulo-interpeduncolar system: selective sparing of metabohc activity. Anesthesiology 56:461–466
Archer DP, Froehch J, McHugh M, et al (1995) Local cerebral glucose utilization in stimulated rats sedated with thiopental. Anesthesiology 83:160–168
Blacklock JB, Oldfield EH, Di Chiro G, et al (1987) Effect of barbiturate coma on glucose utilization in normal brain versus gliomas. Positron emission tomography studies. J Neurosurg 67:71–75
Martin E, Thiel T, Joeri P, et al (2000) Effect of pentobarbital on visual processing in man. Hum Brain Mapp 10:132–139
Dam M, Ori C, Pizzolato G, et al (1990) The effects of propofol anesthesia on local cerebral glucose utilization in the rat. Anesthesiology 73:499–505
Alkire MT, Haier RJ, Barker SJ, et al (1995) Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography. Anesthesiology 82:393–403
Eiset P, Paus T, Daloze T, et al (1999) Brain mechanism of propofol induced loss of consciousness in humans: a positron emission tomography study. J Neurosci 19:5506–5513
Bonhomme V, Eiset P, Meuret P, et al (2001) Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study. J Neurophysiol 85: 1299–1308
Eintrei C, Sokoloff L, Smith CB (1999) Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain. Br J Anaesth 82:596–602
Davis DW, Mans AM, Biebuyck JF, et al (1988) The influence of ketamine on regional brain glucose use. Anesthesiology 69:199–205
Burdett NG, Menon DK, Carpenter TA, et al (1995) Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: preliminary results. Magn Reson Imaging 13:549–553
Ori C, Freo U, Merico A et al (1999) Effects of recovery from anesthesia with ketamine racemic mixture and stereoisomers on local cerebral glucose utilization (LCGU) in rat. XXIX Meetmg of the Society for Neuroscience 25:536
Breier A, Malhotra AK, Finals DA, et al (1997) Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry 154:805–811
Holcomb HH, Lahti AC, Medoff DR, et al (2001) Sequential regional cerebral blood flow brain scans using PET with H2(15)0 demonstrate ketamine actions in CNS dynamically. Neuropsychopharmacology 25:165–172
Lahti AC, Holcomb HH, Medoff DR, et al (1995) Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport 6:869–872
Vollen weider FX, Leenders KL, Oye I (1997) Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol 7:25–38
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Freo, U., Ori, C. (2003). Mapping cerebral metabolic and blood flow effects of general anaesthetics. In: Gullo, A. (eds) Anaesthesia, Pain, Intensive Care and Emergency Medicine — A.P.I.C.E.. Springer, Milano. https://doi.org/10.1007/978-88-470-2215-7_19
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DOI: https://doi.org/10.1007/978-88-470-2215-7_19
Publisher Name: Springer, Milano
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