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Concepts and correlations relevant to general anaesthesia
B.W. Urban, M Bleckwenn British Journal of Anaesthesia Volume 89, Issue 1, Pages 3-16 (July 2002) DOI: /bja/aef164 Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 1 Types of anaesthetic procedures.
British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 2 Components of general anaesthesia, those to be achieved and those to be avoided. Analgesia has been put in brackets because it is already included in other categories; if pain is defined as the conscious awareness of a noxious stimulus, then an unconscious patient may not perceive pain. Immobility includes the abolition of spontaneous movements. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 3 CPK models of (a) inhalation anaesthetics and (b) intravenous anaesthetics. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 3 CPK models of (a) inhalation anaesthetics and (b) intravenous anaesthetics. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 4 Structural formulae and molecular weights (mol. wt) of (a) inhalation anaesthetics and (b) intravenous anaesthetics, including dissociation constants (pKa) where applicable. Note that in a only those hydrogens (H) that are thought to be able to form strong hydrogen bonds are shown. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 4 Structural formulae and molecular weights (mol. wt) of (a) inhalation anaesthetics and (b) intravenous anaesthetics, including dissociation constants (pKa) where applicable. Note that in a only those hydrogens (H) that are thought to be able to form strong hydrogen bonds are shown. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 5 Dates of introduction of anaesthetic drugs.
British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 6 Effect of cholesterol on pentobarbital-induced sodium channel suppression – comparison of sodium channel properties in the absence and presence of cholesterol. The higher the cholesterol concentration, the less effective is pentobarbital, a thiopental analogue, in suppressing currents through sodium channels. (a) Current traces in control (phosphatidylethanolamine and phosphatidylcholine, 4:1 ratio) lipids and with 4% of 50% (weight/weight, corresponding to 7.3 and 65.3 mol% respectively) cholesterol added. Synaptosomal fractions of human brain cortex were prepared, incorporated into planar bilayers in the presence of 250 nM batrachotoxin, and voltage clamped (–40 mV, filtered at 200 Hz). (b) Current traces in the presence of 680 μM pentobarbital. From Rehberg et al.43 with permission. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 7 Comparison of sodium currents (a) and pentobarbital effect (b) in SH-Sy5Y cells (filled circles), N1E-115 cells (filled diamonds), HEK293 cells (grey triangles), and for rat brain (open diamonds) and rat muscle (open triangles) sodium channels expressed in Chinese hamster ovary (CHO) cells. The concentration–response curves for pentobarbital clearly depend on sodium channel subtype, subunit composition and/or cell environment. (a) Voltage dependence of sodium current activation (solid lines) and inactivation (dashed lines). Mean (sem of the fit) potentials of half-maximum activation and inactivation, respectively are –14.9 (3.5) and –65.2 (3.2) for N1E-115; –22.7 (3.4) and –74.7 (10.7) for SH-Sy5Y; –21.4 (4.9) and –62.5 (9.1) for HEK293; –20.9 (8.7) and –53.2 (6.5) for CHO rat brain, and –24.3 (9.6) and –63.0 (7.9) mV for CHO rat muscle. (b) Pentobarbital suppression of maximum inward currents. Lines are fits of a Hill function to the data. Data points are means of 3–5 experiments for SH-SY5Y and HEK293 cells, and of 5–6 experiments for N1E-115 cells. From Rehberg et al.44 with permission. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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Fig 8 Different correlations used in anaesthesia research. (a) Meyer–Overton correlations for MAC in humans and dogs and the righting-reflex EC50 in mice with olive oil/gas partition coefficients. The slopes are almost identical: –0.95, –1.01 and –1.02, respectively. Values are from Table 3-2 in reference 30. (b) The concentrations of alcohols needed to suppress Na+ channels and K+ channels are plotted against the chain length of the alcohols.25 The slopes yield the energy of adsorption of the -CH2 groups of the alcohols to the site of action, consistent with an adsorption to a purely hydrophobic site.25 For the K+ current, however, slope decreases for longer chain alkanols as if they were progressively excluded from a lipophilic environment. Thus it is possible that, with regard to K+ channels, alcohols have two sites of action with differing physicochemical properties. (c) Correlation of IC50 of GABAA channel potentiation with clinical concentrations,55 consistent with GABAA receptor channels playing a role in anaesthesia, but without proving it. (d) NMR hydrogen bond shifts of methoxyflurane (M), chloroform (C), halothane (H), isoflurane (I), and enflurane (E) and their clinical potencies (MAC in man) are correlated (r=0.89),54 consistent with hydrogen bonding playing a role in anaesthesia, but without proving it. British Journal of Anaesthesia , 3-16DOI: ( /bja/aef164) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions
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