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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of anesthesia 11 (1997), S. 292-299 
    ISSN: 1438-8359
    Keywords: Postoperative analgesia ; Regional anesthesia techniques ; Postoperative pain ; Local anesthetics ; Continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 319 (1982), S. 95-100 
    ISSN: 1432-1912
    Keywords: Local anesthetics ; Bupivacaine ; Etidocaine ; Membrane lipids ; Spin labels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been suggested that local anesthetics may block sodium conductance through nervous membranes also by hydrophobic interaction, e.g., by expanding the membrane. Decreased anisotropy (fluidization) and depressed phase transition temperatures have been shown by relatively high local anesthetic concentrations. We studied the dose dependence of the effect of three clinically used local anesthetics, with different lipid solubility, on lipid fluidity parameters of four different model membranes. With stearic acid spin labels in dipalmitoyl lecithin vesicles etidocaine (1–5 mM) had the clearest fluidizing effect followed by bupivacaine (5 mM); 2-chloroprocaine was without effect on lipid fluidity. In synaptic plasma membranes a fluidizing effect near the hydrophilic part of the lipid bilayer was similar with etidocaine and bupivacaine (5–10 mM); 2-chloroprocaine had no effect. Bupivacaine at 125 and 250 μM had a small ordering effect, which was not seen at a more hydrophobic site of the membrane. Etidocaine had the strongest fluidizing effect at the latter site of the synaptic plasma membranes. In erythrocyte ghost membranes, probed by stearic acid spin labels near the hydrophilic end, none of local anesthetics affected fluidity at 24° C, while at 37° C etidocaine (1–5 mM) and bupivacaine (5 mM) had a fluidizing effect. Dimyristoyl lecithin vesicles were probed by cis-and trans-parinaric acid. Etidocaine and bupivacaine (5–10 mM) clearly depressed the phase transition temperature evaluated from fluorescence intensity scans. The effect was most marked with bupivacaine (1–10 mM) when dis-parinaric acid was used. While isolated mammalian nerves are blocked by local anesthetic concentrations below 100 μM, this study shows that the clinically used local anesthetics increase fluidity and depress phase transition temperature only at 10–100 times higher concentrations at physiological pH. This kind of hydrophobic membrane interaction may not be important for the nerve blocking effect.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 199-206 
    ISSN: 1432-1912
    Keywords: Anesthetics, inhalation ; Anesthetics, local ; 5-Hydroxytryptamine ; Membrane lipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although it is agreed that the bilayer lipid region of neural membranes is a principle site of action of general anesthetics, the nature of the action is somewhat controversial, and may depend on the structure of the membranes and the concentration of the anesthetics. Spin-labeled rat brain myelin membranes were shown to have higher order in their bilayer lipid region than that of synaptic plasma membranes, which was in turn higher than that of synaptic mitochondrial membranes, and corresponded to their respective contents of cholesterol (highest in myelin, lowest in mitochondria). Two broad discontinuities in the temperature dependence of the order parameter were observed in the bilayer lipids of all three membranes, a lower one between 12 and 20°C and a higher one between 32 and 38°C. Low concentrations of halothane (0.25 and 0.5 mM) and lidocaine (0.1 mM) increased the order in synaptic plasma membranes, but did not affect myelin or mitochondria membranes in the temperature range between 32 and 42°C. In synaptic plasma membranes the ordering effect of halothane switched to a fluidizing one between anesthetic concentrations of 0.75 and 1.1 mM. High concentrations (2.3 mM halothane and 10 mM lidocaine) decreased the order (fluidized) in all three membranes and was observed most clearly in the hydrophobic region of the lipid bilayer. 5-Hydroxytryptamine (5-HT) at 10−2 and 10−1 mM increased the order in synaptic plasma membranes and at some temperatures also in synaptic mitochondrial membranes, but not in myelin membranes. 5-HT antagonized the fluidizing effect of 2.3 mM halothane and 10 mM lidocaine in synaptic plasma membranes. The antagonism seemed to be only partial in the hydrophilic region of the bilayer lipids in mitochondrial membranes, but total in the hydrophobic region by 10−1 mM 5-HT. Although relatively high concentrations of 5-HT were used, the results showed that this neurotransmitter is able to influence the bilayer lipid fluidity particularly in synaptic plasma membranes. The results, furthermore, indicate that the biphasic dose-dependent effect on lipid fluidity of halothane and lidocaine occurs only in synaptic plasma membranes, and it is suggested that the difference between the degree of fluidity and the responses in the membranes investigated are due to differences in lipid compositions.
    Type of Medium: Electronic Resource
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