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The large number and diversity of anesthetic agents were evident to investigators 80 years ago, and suggested a physicochemical theory of anesthesia. Meyer and Overton were the first to offer a quantitative relationship between a physicochemical property and potency of anesthetic agents. They also focused attention on the lipid phase as the site of anesthetic action. Ferguson realized that the concentration of an agent at its site of action bears a generally unknown relation to the concentration in the external phase. However, at equilibrium the activity of an agent is the same in every phase, motivating Ferguson to suggest that activities rather than concentrations be used as indices of dosage. The critical-volume theory resulted from modification of the Meyer-Overton theory to include the molal volume of the anesthetic. The allowance for molal volume resulted initially from an attempt further to regularize the experimental data. The concept of a critical-volume fraction of anesthetic being necessary for narcosis was discussed in most detail by Mullins. Subsequently, the concept of the effect of the anesthetic has changed from filling of free space to expansion and fluidization of the membrane. The ability of pressure to cause excitant phenomena and antagonize anesthetics is predictable from the critical-volume theory and is therefore highly significant evidence. K. W. Miller and associates are perhaps most prominent in the recent quantification and formalization of the critical-volume theory and HPNS. The existence of a separate convulsant site(s) is suggested by the demonstration of significantly different compressibilities associated with anesthesia and convulsions. Work corroborating a separate convulsant site involved measurement of the partial molal volumes of a series of related convulsant and anesthetic ethers and calculation of each compound's solubility parameter. Multiple convulsant sites may exist, and these two methods may not have accessed the same site. Understanding the anesthetic-convulsant duality will have important practical application to deepwater diving, and may well offer important insight into the neurophysiologic and electrophysiologic effects of anesthetics. The application of ESR and NMR allows investigation at the molecular level of effects of anesthetics on biological and model membranes. Magnetic resonance techniques have generally supported the concept of membrane fluidization by anesthetics. Some investigators have recently attempted to displace the focus of attention from the lipid phase. However, the evidence is clearly against the aqueous-phase theory of Pauling and S.L. Miller. The microtubule theory of Allison and Nunn has not accumulated supporting evidence comparable to the lipid theories. Contradictory evidence makes any evaluation of this theory speculative. Additionally, the interspecies and intracellular variability of microtubules raises questions of the relevance of many studies...
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PMID:Biophysical mechanisms of anesthetic action: historical perspective and review of current concepts. 18 56

The polymorphic phase behaviour of model membrane systems consisting of 20 mol% bovine brain phosphatidylserine and 80 mol% egg yolk phosphatidylethanolamine has been examined employing 31P NMR techniques. It is shown that the addition of Ca2+ to such systems can trigger isothermal bilayer to hexagonal (HII) phase transitions, and that such effects can be reversed by the subsequent incorporation of the local anaesthetic dibucaine. These results are discussed in terms of a recent model for membrane fusion (Cullis, P.R. and Hope, M.J. (1978) Nature 271, 672--674) and mechanisms of anaesthesia.
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PMID:Modulation of membrane structure by Ca2+ and dibucaine as detected by 31P NMR. 57 38

The interactions between amine local anesthetic dibucaine and pig erythrocyte membranes have been studied by proton and phosphorus-31 nuclear magnetic resonance (1H- and 31P-NMR) spectroscopy. It was found that dibucaine, bound to the membranes, increases the mobility of the hydrophobic acyl chains of the phospholipids, but that it decreases the mobility and/or changes the structure of the polar headgroups. The interactions with peripheral membrane proteins, i.e., spectrin and actin, were found to be weak. These observations indicate that the dibucaine locates across the polar and hydrophobic areas of the lipid phase of the membranes by both electrostatic and hydrophobic interactions. It is assumed that the changes in the mobility and/or the conformation of the phospholipids residing around the Na channel protein are essential in causing anesthesia.
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PMID:Interactions between local anesthetic dibucaine and pig erythrocyte membranes as studied by proton and phosphorus-31 nuclear magnetic resonance spectroscopy. 132 58

Anaesthetic concentration is very important for the quantitative treatment of anaesthesia theory. Traditionally concentration values have been derived from the water/gas partition coefficient. However, the values from many investigators show discrepancies. This study reports the accurate solubility of methoxyflurane (9.1 mM), halothane (18.0 mM), enflurane (11.9 mM) and isoflurane (13.5 mM) in water at 25.0 degrees C using 19F NMR spectroscopy. The method has advantages in that the dissolved molecule in solution can be separately quantified from undissolved anaesthetic. Saturated solutions of the anaesthetic agents were prepared in situ in a NMR tube to avoid pressure and temperature changes in the solution.
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PMID:The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy. 139 Oct 78

Immobilization of laboratory animals is a basic requirement for experimental in vivo NMR measurements. The effect of single and repeated isoflurane anesthesia on proton NMR relaxation times T1 and T2 in rat liver was studied. Furthermore, physiological monitoring was performed to evaluate the influence of isoflurane anesthesia (up to 2 hr) on biological parameters. Neither single nor repeated isoflurane application over the observed time produce relevant alterations of physiological parameters or relaxation times, compared with untreated control groups. Therefore, we conclude that isoflurane anesthesia is appropriate for in vivo NMR investigations, especially of the liver.
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PMID:In vitro NMR investigation of controlled single and repeated isoflurane anesthesia. 140 89

A case of paraplegia occurring after a spinal anaesthetic is reported. The 79-year-old man was admitted for a fractured neck of femur. Twenty years previously, he had had pharyngeal surgery and a tracheostomy. He had also undergone a prostatectomy for prostate cancer, and had been on oestrogen therapy for two years. He complained of dyspnoea at rest and his chest film showed diffuse pulmonary opacities. In order to avoid possible intubation and respiratory complications, spinal anaesthesia was performed without any problems in the L4 space. After the surgery, the patient recovered all his motor and sensory functions in the lower limbs. On the second postoperative day, he suffered from a motor paralysis of the right leg, which spread to the left leg on the fourth day. NMR imaging showed several vertebral metastases, together with anterior and lateral epidural invasion responsible for cord compression. Treatment with tetracosactide was begun, but the patient died six weeks later in his home, not having recovered any neurological function at all in his lower limbs. In fact, it was only after the procedure that the anaesthetist was informed that, at the time the prostate cancer had been diagnosed, vertebral body metastases, of which the patient had not been informed, were already present. The part played by the spinal anaesthetic in the occurrence of the paraplegia is not clear. It is reminded that such a technique should be used with extreme care in patients having a neoplasm with a very often high incidence of vertebral metastases.
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PMID:[Paraplegia after spinal anesthesia]. 150 98

A series of 8 new derivatives of 2-alkoxyphenylcarbamoic acid were synthesized and assayed for local anesthetic activity. The above compounds were isolated as hydrochlorides and their structure was proved by 1H NMR, 13C NMR and IR spectroscopy. The index of anesthetic activity of the compounds in infiltration and surface anesthesia increases with the length of the alkyl chain and, except for the C1-C3 congeners, all higher homologues proved to be significantly more active than the standard reference compounds, procaine and cocaine, respectively. Toxicity of the drugs decreases with increasing the chain length and is within acceptable limits.
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PMID:Synthesis and local anesthetic activity of some derivatives of N,N-dimethyl-2-(2-alkoxyphenylcarbamoyloxy)-1,1-dimethylethyl-ammonium chlorides. 150 96

Energy metabolism of the cat brain was studied using phosphorous-31 nuclear magnetic resonance (31P-NMR) during sevoflurane/halothane anesthesia with normo- and hyperventilation. Under normocapnia, the findings associated with abnormal energy metabolism were not observed at concentration of sevoflurane/halothane up to 2 MAC. Meanwhile under hypocapnia by hyperventilation, the value of phosphocreatine began to decrease at and below 20 mmHg of PaCO2 (2 MAC sevoflurane) and 30 mmHg of PaCO2 (2 MAC halothane) respectively. These abnormal findings of brain metabolism were limited to the cases with cerebral blood flow (CBF) of less than a half of control state (nonanesthetized and normoventilated), and they were normalized with increased CBF by the vasoconstrictor, metaraminol. From the above data, it was concluded that the deteriorated energy metabolism by hyperventilation was due to decrease in CBF with hypotension and there was no direct effect on cerebral metabolism with less than 2MAC of both sevoflurane and halothane.
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PMID:[The effects of sevoflurane/halothane anesthesia during normo- and hyperventilation on the energy metabolism of the cat brain]. 154 5

Measurement of tissue perfusion is important for the functional assessment of organs in vivo. Here we report the use of 1H NMR imaging to generate perfusion maps in the rat brain at 4.7 T. Blood water flowing to the brain is saturated in the neck region with a slice-selective saturation imaging sequence, creating an endogenous tracer in the form of proximally saturated spins. Because proton T1 times are relatively long, particularly at high field strengths, saturated spins exchange with bulk water in the brain and a steady state is created where the regional concentration of saturated spins is determined by the regional blood flow and regional T1. Distal saturation applied equidistantly outside the brain serves as a control for effects of the saturation pulses. Average cerebral blood flow in normocapnic rat brain under halothane anesthesia was determined to be 105 +/- 16 cc.100 g-1.min-1 (mean +/- SEM, n = 3), in good agreement with values reported in the literature, and was sensitive to increases in arterial pCO2. This technique allows regional perfusion maps to be measured noninvasively, with the resolution of 1H MRI, and should be readily applicable to human studies.
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PMID:Perfusion imaging. 173 82

The effect of anesthesia on the epimerization of 2-deoxy-2-fluoro-D-glucose(-6-phosphate) to 2-deoxy-2-fluoro-D-mannose(-6-phosphate) in mice was demonstrated with 19F NMR spectroscopy of excised tissue specimens from heart, muscle, and brain. Spectra from each of six excised organs confirmed that pretreatment with an anesthetic suppressed the conversion ratio, FDM/(FDG + FDM), in brain at 3 h from 52 +/- 5 to 30 +/- 6% under the dose of 100 mg/kg. We propose potential applications for NMR monitoring of FDG-FDM conversion, including the assessment of regional brain metabolism and the evaluation of various pharmacologic agents.
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PMID:Evaluation of energy metabolism in brain using epimerization of 2-deoxy-2-fluoro-D-glucose by 19F NMR: the effect of anesthesia. 174 18


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