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PubMed2004

Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions.

This study directly examines the enthalpic contributions to binding in aqueous solution of closely related anesthetic haloethers (desflurane, isoflurane, enflurane, and sevoflurane), a haloalkane (halothane), and an intravenous anesthetic (propofol) to bovine and human serum albumin (BSA and HSA) using isothermal titration calorimetry. Binding to serum albumin is exothermic, yielding enthalpies (DeltaH(obs)) of -3 to -6 kcal/mol for BSA with a rank order of apparent equilibrium association constants (K(a) values): desflurane > isoflurane approximately enflurane > halothane >or= sevoflurane, with the differences being largely ascribed to entropic contributions. Competition experiments indicate that volatile anesthetics, at low concentrations, share the same sites in albumin previously identified in crystallographic and photo-cross-linking studies. The magnitude of the observed DeltaH increased linearly with increased reaction temperature, reflecting negative changes in heat capacities (DeltaC(p)). These -DeltaC(p) values significantly exceed those calculated for burial of each anesthetic in a hydrophobic pocket. The enhanced stabilities of the albumin/anesthetic complexes and -DeltaC(p) are consistent with favorable solvent rearrangements that promote binding. This idea is supported by substitution of D(2)O for H(2)O that significantly reduces the favorable binding enthalpy observed for desflurane and isoflurane, with an opposing increase of DeltaS(obs). From these results, we infer that solvent restructuring, resulting from release of water weakly bound to anesthetic and anesthetic-binding sites, is a dominant and favorable contributor to the enthalpy and entropy of binding to proteins.

Anesthetics, Inhalation↗

PubMed1999

Different anesthetic sensitivities of skeletal and cardiac isoforms of the Ca-ATPase.

We have previously shown that low levels of the volatile anesthetic halothane activate the Ca-ATPase in skeletal sarcoplasmic reticulum (SR), but inhibit the Ca-ATPase in cardiac SR. In this study, we ask whether the differential inhibition is due to (a) the presence of the regulatory protein phospholamban in cardiac SR, (b) different lipid environments in skeletal and cardiac SR, or (c) the different Ca-ATPase isoforms present in the two tissues. By expressing skeletal (SERCA 1) and cardiac (SERCA 2a) isoforms of the Ca-ATPase in Sf21 insect cell organelles, we found that differential anesthetic effects in skeletal and cardiac SR are due to differential sensitivities of the SERCA 1 and SERCA 2a isoforms to anesthetics. Low levels of halothane inhibit the SERCA 2a isoform of the Ca-ATPase, and have little effect on the SERCA 1 isoform. The biochemical mechanism of halothane inhibition involves stabilization of E2 conformations of the Ca-ATPase, suggesting direct anesthetic interaction with the ATPase. This study establishes a biochemical model for the mechanism of action of an anesthetic on a membrane protein, and should lead to the identification of anesthetic binding sites on the SERCA 1 and SERCA 2a isoforms of the Ca-ATPase.

Anesthetics, Inhalation↗

PubMed1982

Hydrogen bonding and anesthetic potency.

Hydrogen bond strengths in terms of the proton chemical shifts of five potent inhalation anesthetics containing acidic hydrogen were measured in cyclohexane and in methanol using the proton magnetic resonance spectroscopic method. The purpose of this study is to quantitatively compare the relative polar character of potent anesthetics. The hydrogen bond shift (delta ppm) of each anesthetic is the difference in the chemical shifts of the infinitely diluted unassociated anesthetic in cyclohexane and that of the infinitely diluted hydrogen bonded anesthetic in methanol. It was found that the hydrogen bond shifts (in delta ppm) are as follows: methoxyflurane, 0.72; chloroform, 0.75; halothane, 1.06; isoflurane, 1.38; enflurane, 1.44. There is a good correlation between the hydrogen bond shifts and the clinical potencies (minimum alveolar concentration in man). The conclusion from this study is that the acidic halogenated inhalation anesthetics are more potent if they form weaker hydrogen bonds.

Anesthetics↗

PubMed2003

Neurosteroid analogues. 9. Conformationally constrained pregnanes: structure-activity studies of 13,24-cyclo-18,21-dinorcholane analogues of the GABA modulatory and anesthetic steroids (3alpha,5alpha)- and (3alpha,5beta)-3-hydroxypregnan-20-one.

The hydrogen-bond-acceptor properties of the carbonyl moiety in the 17beta-acetyl group on the D-ring of the anesthetic steroids (3alpha,5alpha)- and (3alpha,5beta)-3-hydroxypregan-20-one form an important part of the anesthetic steroid pharmacophore. 13,24-Cyclo-18,21-dinorcholanes containing a ketone or conjugated ketone group at C-20, C-22, C-23, or C-24 were prepared as conformationally constrained analogues of these anesthetic steroids and were used to probe for alternate locations for the D-ring hydrogen-bond-accepting carbonyl group. The analogues were evaluated (1). in [(35)S]-tert-butylbicyclophosphorothionate binding experiments, (2). in electrophysiological experiments using rat alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes, and (3). as tadpole anesthetics. In the binding assay, the relative order of potencies for the analogues in the 5alpha- and 5beta-series is identical. For the ketones, the order is 24-one >or= 23-one > 20-one > 22-one. Likewise, for the enones, the order is delta(22)-24-one > delta(20(22))-23-one > delta(22)-20-one > delta(23)-22-one. Similar relative orders of potencies are also found in the other two bioassays. The activities of the 24-one and delta(22)-24-one compounds were expected to be very low, because the carbonyl group in these compounds is located over the steroid C-ring and oriented toward C-8. Instead, these compounds have the highest activities in their respective series, with the delta(22)-24-one compounds having activities comparable to those of the reference anesthetic steroids. The electrophysiology results obtained with the 24-oxo-cyclosteroids suggest that rat alpha(1)beta(2)gamma(2L) GABA(A) receptors contain more than one donor for the hydrogen-bond-acceptor group of anesthetic steroids. The family of cyclosteroids should be useful for future structure-activity relationship studies of steroid modulation of other GABA(A) receptor subtypes.

Anesthetics↗

PubMed1999

Waste gas monitor reduces wasted volatile anesthetic.

OBJECTIVE: The increasing focus on health care costs requires that all physicians evaluate practice behaviors. The primary emphasis in anesthesia has been limiting the use of expensive medications and interventions. Reducing waste is another approach, and volatile anesthetics are an appropriate target in that simple reduction of fresh gas-flow (FGF) rates is effective. A monitor that measures and displays the cost of wasted volatile anesthetic was developed and used to determine if real-time display of the cost would result in decreased FGF rates, which, in turn, would decrease wasted anesthetic. METHODS: The waste gas monitor (WGM) measures flow rate at the anesthesia machine's scavenger port, integrates this with agent concentration, and displays the calculated cost, real-time, on a portable computer screen. The WGM equipment was attached to the anesthesia machine in the gynecologic surgery operating room (OR) and those cases performed under general endotracheal anesthesia and lasting longer than one hour were eligible for inclusion. First year anesthesiology residents assigned to the study OR as part of a non-specialty rotation, were the subjects of the study. For each resident, after data were collected from at least two eligible baseline cases (Baseline Phase, WGM not visible and resident unaware of its presence), the monitor was introduced and data collection continued for at least three more eligible cases (Visible Phase). RESULTS: Nine residents were initially enrolled, but due to scheduling difficulties only five residents completed the protocol. Data from cases using the WGM demonstrated a 50% decrease (3.58 +/- 1.34 l/min vs. 1.78 +/- 0.51 l/min (p = 0.009)) in the scavenger flow rates, which resulted in a 48% ($5.28 +/- 0.68 vs. $2.72 +/- 0.80 (p = 0.002)) decrease in hourly cost of wasted volatile anesthetic. There was no difference between the Baseline and Visible phases with regard to use of nitrous oxide or intravenous anesthetic agents. CONCLUSIONS. The WGM decreased wasted volatile anesthetic by encouraging decreased FGF rates.

Anesthetics, Inhalation↗

PubMed1998

Epidermal iontophoresis: II. Application of the ionic mobility-pore model to the transport of local anesthetics.

PURPOSE: An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. METHODS: The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. RESULTS: The logarithm of the iontophoretic permeability coefficient (log PC(j,iont)) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PC(j,iont) was best defined by ionic mobility (and its determinants: conductivity, pKa and MW) and MW. CONCLUSIONS: Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pKa) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.

Anesthetics, Local↗

PubMed1998

Fluorinated anesthetic exposure "activates" the renal cortical sphingomyelinase cascade.

BACKGROUND: Previous studies indicate that fluorinated anesthetics can enhance sphingomyelin (SM) hydrolysis in in vitro neuronal extracts. Renal cortex has substantial SM content. Hence, this study assessed whether in vivo fluorinated anesthetic use stimulates renal SM hydrolysis, causing accumulation of ceramide, an important signaling molecule. METHODS: Mice were anesthetized with isoflurane or desflurane (fluorinated anesthetics). Pentobarbital anesthetized mice served as controls. After six hours, kidney cortex was assayed for ceramide. In selected experiments, renal cortical sphingosine and sphingomyelinase (SMase) levels were also determined. Isoflurane's effects on ceramide levels in cultured human proximal tubule (HK-2) cells/isolated mouse proximal tubule segments (PTS), and on in vitro 14C-SM hydrolysis were also assessed. RESULTS: Isoflurane and desflurane, but not pentobarbital, increased renal cortical ceramide levels (such as, 65% with isoflurane, P < 0.003). Isoflurane also raised PTS/HK-2 ceramide levels (by 25 to 35%). Ceramidase inhibition (fumonisin B1) did not block this ceramide accumulation in HK-2 cells. Isoflurane did not increase renal cortical/PTS SMase levels. However, it directly enhanced the ability of (acidic) SMase to effect in vitro 14C-SM hydrolysis. Isoflurane raised renal cortical sphingosine (and not just ceramide) levels, implying ongoing ceramidase activity. CONCLUSIONS: Fluorinated anesthetics can stimulate renal cortical/tubule ceramide expression, presumably by stimulating SMase-mediated SM hydrolysis. Since ceramide is a potential mediator of tubule apoptosis/necrosis, these findings have potential relevance for the development of intra/post-operative acute renal failure.

Anesthetics, Inhalation↗

PubMedDate not supplied

Restricted infraclavicular distribution of the local anesthetic solution after infraclavicular brachial plexus block.

BACKGROUND AND OBJECTIVES: The distribution of local anesthetic after different approaches for brachial plexus anesthesia could be responsible for the varying rates of side effects, such as phrenic block, hoarseness, and Horner's syndrome associated with each approach. We compared the distribution of local anesthetic within the neurovascular space in infraclavicular block with that of interscalene and supraclavicular block. METHODS: In a prospective analysis using fluoroscopy, we studied the distribution of a solution of local anesthetic containing radiologic contrast medium in 18 patients. Six patients received an interscalene block, another 6 patients received a perpendicular supraclavicular block, and another 6 patients, a perpendicular coracoid block. RESULTS: Distribution of the anesthetic solution in the interscalene and supraclavicular groups extended to both supraclavicular and infraclavicular spaces in all patients. This distribution was significantly different (P <.05) compared with that of the infraclavicular group. In this group, the solution remained below the clavicle in every patient. CONCLUSIONS: Spread of the local anesthetic from the infraclavicular space after infraclavicular coracoid block appears to be limited to below the level of the clavicle. Conversely, local anesthetic solution passes below the clavicle in all patients given interscalene or supraclavicular blocks.

Amides↗

PubMed2000

Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.

Ligand-gated ion channels are a target for inhaled anesthetics and alcohols in the central nervous system. The inhibitory strychnine-sensitive glycine and gamma-aminobutyric acid type A receptors are positively modulated by anesthetics and alcohols, and site-directed mutagenesis techniques have identified amino acid residues important for the action of volatile anesthetics and alcohols in these receptors. A key question is whether these amino acids are part of an alcohol/anesthetic-binding site. In the present study, we used an alkanethiol anesthetic to covalently label its binding site by mutating selected amino acids to cysteine. We demonstrated that the anesthetic propanethiol, or alternatively, propyl methanethiosulfonate, covalently binds to cysteine residues introduced into a specific second transmembrane site in glycine receptor and gamma-aminobutyric acid type A receptor subunits and irreversibly enhances receptor function. Moreover, upon permanent occupation of the site by propyl disulfide, the usual ability of octanol, enflurane, and isoflurane to potentiate the function of the ion channels was lost. This approach provides strong evidence that the actions of anesthetics in these receptors are due to binding at a single site.

Alcohols↗

PubMed1976

Nuclear magnetic resonance studies of the interaction of general anesthetics with 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine bilayer.

Sonicated 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine forms liposomes. Studies by Fourier transform proton magnetic resonance of the interaction of these bilayers with some general anesthetics, i.e., chloroform, halothane, methoxyflurane, and enflurane, show that the addition of a general anesthetic to the liposomes and raising the temperature have a similar effect in cuasing the fluidization of the bilayer. General anesthetics act on the hydrophilic site (choline group) in clinical concentrations and then diffuse into the hydrophobic region with the addition of larger amount of anesthetics. There is evidence that the lecithin choline groups are involved in the interaction with protein and that the general anesthetics change the conformation of some polypeptides and proteins. We conclude that the general anesthetics, by increasing the motion of positively charged choline groups and negatively charged groups in protein, weaken the Coulomb-type interaction and cause the liprotein conformational changes.

Anesthetics↗

PubMed1981

Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin.

Local anesthetics such as dibucaine, QX572, tetracaine, and phenacaine, as well as other drugs with local anesthetic-like properties (e.g., mepacrine, propranolol, and SKF 525A) inhibit the specific calmodulin-dependent stimulation of erythrocyte Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and cyclic nucleotide phosphodiesterases (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) from brain and heart. Basal activities of these enzymes in the absence of calmodulin are relatively unaffected by concentrations of local anesthetics that strongly inhibit the specific stimulation by calmodulin. Increasing calmodulin, but not Ca2+, overcomes the inhibitory action of the local anesthetics on brain phosphodiesterase. However, excess calmodulin does not fully restore activity of erythrocyte CA2+-stimulated ATPase. Although the mechanism(s) by which the local anesthetics act is unclear, they inhibit binding of 125I-labeled calmodulin to the erythrocyte membrane. Antagonism of calmodulin provides a molecular mechanism that may explain the inhibition of many Ca2+-dependent cellular processes by local anesthetics--e.g., Ca2+ transport, exocytosis, excitation-contraction coupling, non-muscle-cell motility, and aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Binding of the volatile anesthetic chloroform to albumin demonstrated using tryptophan fluorescence quenching.

The site(s) of action of the volatile general anesthetics remain(s) controversial, but evidence in favor of specific protein targets is accumulating. The techniques to measure directly volatile anesthetic binding to proteins are still under development. Further experience with the intrinsic protein fluorescence quenching approach to monitor anesthetic-protein complexation is reported using chloroform. Chloroform quenches the steady-state tryptophan fluorescence of bovine serum albumin (BSA) in a concentration-dependent, saturable manner with a Kd = 2.7 +/- 0.2 mM. Tryptophan fluorescence lifetime analysis reveals that the majority of the quenching is due to a static mechanism, indicative of anesthetic binding. The ability of chloroform to quench BSA tryptophan fluorescence was decreased markedly in the presence of 50% 2,2,2-trifluoroethanol, which causes loss of tertiary structural contacts in BSA, indicating that protein conformation is crucial for anesthetic binding. Circular dichroism spectroscopy revealed no measurable effect of chloroform on the secondary structure of BSA. The results suggest that chloroform binds to subdomains IB and IIA in BSA, each of which contains a single tryptophan. Earlier work has shown that these sites are also occupied by halothane. The present study therefore provides experimental support for the theory that structurally distinct general anesthetics may occupy the same domains on protein targets.

Anesthetics, Inhalation↗

PubMed2001

Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor function.

Recent studies suggest that alcohols, volatile anesthetics, and inhaled drugs of abuse, which enhance gamma-aminobutyric acid, type A, and glycine receptor-activated ion channel function, may share common or overlapping molecular sites of action on these receptors. To investigate this possibility, these compounds were applied singly and in combination to wild-type glycine alpha(1) receptors expressed in Xenopus laevis oocytes. Data obtained from concentration-response curves of the volatile anesthetic enflurane constructed in the presence and absence of ethanol, chloroform, or toluene were consistent with competition for a common binding pocket on these receptors. A mutant glycine receptor, insensitive to the enhancing effects of ethanol but not anesthetics or inhalants, demonstrated antagonism of anesthetic and inhalant effects on this receptor. Although ethanol (25-200 mm) had no effect on its own in this receptor, it was able to inhibit reversibly the enhancing effect of enflurane, toluene, and chloroform in a concentration-dependent manner. These data suggest the existence of overlapping molecular sites of action for ethanol, inhalants, and volatile anesthetics on glycine receptors and illustrate the feasibility of pharmacological antagonism of the effects of volatile anesthetics.

Anesthetics, Inhalation↗

PubMed2004

Considerations in selecting an inhaled anesthetic agent: case studies.

PURPOSE: Product and patient-specific factors that may influence the selection of an inhaled anesthetic agent are discussed in four case studies. SUMMARY: The cardiovascular, respiratory, hepatic, and renal effects of various inhaled anesthetic agents vary and may be important in selecting an agent for patients with impairment of these systems. The extent to which anesthetics are metabolized and the risk of hepatotoxicity also vary. Halothane is associated with a relatively high risk for arrhythmias and hepatotoxicity. It also has a high solubility in tissues and is associated with a slow onset and termination of effect and recovery. Pharmacokinetic and pharmacodynamic differences among anesthetics may be important considerations, depending on the surgical setting, anticipated duration of surgery, whether endotracheal intubation is used, and other patient-specific factors such as body weight and age. The duration of surgery is an important consideration for most patients because differences between inhaled anesthetics in offset of effect vary with the duration of the procedure. Desflurane or sevoflurane may be preferred for obese patients because of a faster recovery and greater respiratory safety compared with isoflurane. Sevoflurane is preferred for pediatric patients undergoing induction by inhalation because of its low propensity to cause respiratory irritation. CONCLUSION: There are many product- and patient-specific factors that pharmacists must take into account when selecting an inhaled anesthetic agent. It is important to consider all of these factors when developing the pre- and post-anesthesia plan.

Adult↗

PubMed2006

Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex.

Functional magnetic resonance imaging (fMRI) in anesthetized rodents has been commonly performed with alpha-chloralose, which can be used only for terminal experiments. To develop a survival fMRI protocol, an isoflurane (ISO) -anesthetized rat model was systematically evaluated by simultaneous measurements of field potential (FP) and cerebral blood flow (CBF) in the somatosensory cortex. A conventional forepaw stimulation paradigm with 0.3 ms pulse width, 1.2 mA current, and 3 Hz frequency induced 54% less evoked FP and 84% less CBF response under ISO than alpha-chloralose. To improve stimulation-induced responses under ISO, 10-pulse stimulations were performed with variations of width, current, and frequency. For widths of 0.1-5.0 ms and currents of 0.4-2.0 mA, evoked FP and CBF increased similarly and reached a plateau. The evoked FP increased monotonically for intervals from 50 to 500 ms, but the CBF peaked at an interval of 83 ms (approximately 12 Hz frequency). These data suggest that different anesthetics profoundly affect FP and CBF responses in different ways, which requires optimizing stimulation parameters for each anesthetic. With the refined stimulation parameters, fMRI consistently detected a well-localized activation focus at the primary somatosensory cortex in ISO-anesthetized rats. Thus, the ISO-anesthetized rat model can be used for cerebrovascular activation studies, allowing repeated noninvasive survival experiments.

Anesthetics, Inhalation↗

PubMed1992

Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons.

A volatile anesthetic-gated current was characterized in patch-clamped cultured postnatal rat hippocampal neurons. In this preparation, the major volatile anesthetics, isoflurane, halothane, and enflurane, open an anion-selective conductance. This volatile anesthetic-gated current exhibits anion selectivity with a chloride-to-acetate permeability ratio of 15, shows outward rectification well described by the constant field equation, and is activated in a dose-dependent fashion with half-maximal response to isoflurane at 0.8 mM (0.032 atm). The current persists in the absence of external Ca2+ and is not blocked by strychnine, a glycine antagonist. However, the gamma-aminobutyric acidA (GABAA) antagonists, bicuculline and picrotoxinin, and the nonspecific anion channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), completely block the response. These observations suggest that volatile anesthetics, like several other general anesthetics such as barbiturates, steroids, and etomidate, have a GABA-mimetic effect on vertebrate central neurons in culture. It is not clear whether this GABAA-gating property is a prerequisite for all general anesthetics. However, under normal physiological conditions of low intracellular Cl-, it is likely that drugs with both direct GABA agonist and GABA modulatory properties will produce overall depression of the central nervous system by increasing the normal inhibitory synaptic influence and by directly hyperpolarizing neurons.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1997

The anesthetic effect of dexmedetomidine does not adhere to the Meyer-Overton rule but is reversed by hydrostatic pressure.

To test the hypothesis that the anesthetic action of dexmedetomidine is similar to that of other anesthetics, dexmedetomidine was studied using two classical descriptors of anesthesia, the Meyer-Overton correlation and the pressure reversal of anesthesia. The anesthetic potency of dexmedetomidine and its isomer, levomedetomidine, were determined in Xenopus laevis tadpoles. Anesthesia was defined as loss of righting reflex. Octanol/water partition coefficients were determined using ultraviolet absorbance spectrophotometry. Pressure experiments were performed at pressures ranging from 1 to 91 atmospheres absolute (ata). A concentration-response curve was obtained with a half-maximum effective concentration (EC50) of dexmedetomidine of 7.1 +/- 1.1 microM (mean +/- SEM), whereas levomedetomidine showed an EC50 of 59.3 +/- 5.5 microM. The octanol/water partition coefficient was 206 +/- 49. With increasing pressure, the EC50 of dexmedetomidine increased linearly up to a value of 23.9 +/- 3.2 microM at 91 ata. Correlation of lipid solubility and anesthetic potency demonstrates that dexmedetomidine does not adhere to the Meyer-Overton rule. However, the anesthetic action of dexmedetomidine is diminished by increased pressures, thus demonstrating a similar effect compared with other general anesthetics.

Anesthetics↗

PubMed1997

Minimum alveolar anesthetic concentration values for the enantiomers of isoflurane differ minimally.

Results of in vivo and in vitro studies of the anesthetic potencies of the enantiomers (optical isomers) of isoflurane provide various results ranging from no difference to differences of nearly two fold. A finding of a difference in anesthetic requirement in the whole animal has particular relevance to theories of anesthetic mechanisms of action because it suggests that anesthesia may result from a specific anesthetic-receptor interaction. This led to our decision to redetermine the minimum alveolar anesthetic concentration (MAC) of (+)-S and (-)-R enantiomers of isoflurane in 12 Sprague-Dawley rats (six per group). The (+)-S enantiomer gave a MAC of 0.0144 +/- 0.0012 atm (i.e., 1.44% +/- 0.12% at 1 atm pressure; mean +/- SD) and the (-)-R enantiomer gave a MAC of 0.0169 +/- 0.0020 atm. Although the 17% greater value for the (-)-R enantiomer is qualitatively consistent with previous results the difference is not significant (P = 0.06), and the absolute difference is smaller than that found by a previous study. However, given the small sample size, our power to define a small significant difference is limited. Regardless of statistical significance, our results do not confirm the conclusion that interaction with a specific receptor is important to the mechanism of action of inhaled anesthetics.

Anesthetics, Inhalation↗