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PubMed1989

Pituitary thyrotropin-releasing hormone receptors: local anesthetic effects on binding and responses.

Pharmacological agents are widely used to probe the mechanism of action of TRH. A number of these drugs behave as local anesthetics at high concentrations. The effect of local anesthetics on the binding of [3H]Me-TRH to specific receptors was studied using the GH4C1 line of rat pituitary tumor cells. [3H]Me-TRH binding was inhibited by classical local anesthetics with the order of potency (IC50 values): dibucaine (0.37 mM) greater than tetracaine (1.2 mM) greater than lidocaine (3.3 mM) greater than procaine and benzocaine (greater than 10 mM). IC50 values for other drugs with local anesthetic properties that inhibited [3H]Me-TRH were: 100 microM trifluoperazine, 100 microM imipramine, 170 microM chlorpromazine, 300 microM verapamil, and 700 microM propranolol. Inhibition by tetracaine and verapamil increased as the pH was raised from 6 to 8.5, indicating that the free base form of the amine drugs was the inhibitory species, and the local anesthetic effect was greater at 37 C than at 24 C or 0 C. [3H]Me-TRH binding to receptors in isolated membranes was inhibited to the same extent as binding to receptors on intact cells. Local anesthetics were 3- to 20-fold less potent at inhibiting [3H]Me-TRH to digitonin-solubilized receptors than binding to intact cells. In contrast, the potency of chlordiazepoxide, a putative TRH antagonist, to inhibit [3H]Me-TRH binding was equal using cells and solubilized receptors (IC50 = 10 microM). Local anesthetics inhibited TRH-stimulated PRL release and also inhibited basal PRL secretion and secretion stimulated by two nonhormonal secretagogues, (Bu)2cAMP and a phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗

PubMedDate not supplied

Trace concentrations of anesthetic gases: a critical review of their disease potential.

Only high levels of anesthetics and long times of exposure cause significant histotoxicity in laboratory studies on cells and animals. The disease-provoking mechanism involves profound physiological phenomena associated with anesthesia. Trace concentrations of anesthetics produce none of these effects. Therefore, studies using high concentrations have no value in predicting the effects of trace concentrations. Laboratory studies show that none of the most commonly used halogenated anesthetics produces cancer in animals. Epidemiological studies show no correlation between anesthetics and cancer in men and only a dubious correlation in women. The epidemiological studies to date on reproductive disease are inconclusive. They have not been designed to eliminate errors of data gathering or statistics. Nor have they been designed to test the cause-effect relationship between trace concentrations of anesthetics and reproductive disease. Anesthesiologists have a lower mortality rate than physicians as a whole. Conservative environmental health standards suggest that anesthetic levels in excess of those found in unscavenged operating rooms should be nontoxic. There are no statistically sound studies which prove that trace concentrations of anesthetic gases exert harmful effects.

Abortion, Spontaneous↗

PubMed1992

Blood flow and tissue oxygen pressures of liver and pancreas in rats: effects of volatile anesthetics and of hemorrhage.

The object of this investigation was to compare the effects of volatile anesthetics and of hemorrhage at comparable arterial blood pressures on splanchnic blood flow (radioactive microspheres) and tissue oxygenation of the liver and pancreas (surface PO2 [PSO2] electrodes). In contrast to earlier studies, we did not use identical minimum alveolar anesthetic concentration multiples as a reference to compare volatile anesthetics; rather, we used the splanchnic perfusion pressure. Under general anesthesia (intravenous chloralose) and controlled ventilation, 12 Sprague-Dawley rats underwent laparotomy to allow access to abdominal organs. Mean arterial pressure was decreased from 84 +/- 3 mm Hg (mean +/- SEM) at control to 50 mm Hg by 1.0 +/- 0.1 vol% halothane, 2.2 +/- 0.2 vol% enflurane, and 2.3 +/- 0.1 vol% isoflurane in a randomized sequence. For hemorrhagic hypotension, blood was withdrawn gradually until a mean arterial pressure of 50 mm Hg was attained. Volatile anesthetics and hemorrhage reduced cardiac output, and hepatic arterial, portal venous, and total hepatic blood flows by comparable degrees. Mean hepatic PSO2 decreased significantly from 30.7 +/- 2.6 mm Hg at control to 17.4 +/- 2 and 17.5 +/- 2 mm Hg during enflurane and isoflurane (each P less than 0.05) anesthesia, respectively. The decrease to 11.5 +/- 2.5 mm Hg was more pronounced during halothane anesthesia. Hemorrhagic hypotension was associated with the lowest hepatic PSO2 (3.4 +/- 1.3 mm Hg) and the highest number of hypoxic (0-5 mm Hg 86%) and anoxic PSO2 values (0 mm Hg 46%). Pancreatic blood flow and oxygenation remained unchanged from control during halothane and enflurane administration, whereas isoflurane increased both variables. Hemorrhagic hypotension slightly reduced pancreatic flow (-8%) but significantly decreased PSO2 from 58 +/- 5 mm Hg at control to 36 +/- 3 mm Hg, with 7% of all measured values in the hypoxic range. Thus, volatile anesthetics preserved pancreatic but not hepatic blood flow and tissue oxygenation in this rat model. Despite comparable effects on perfusion, the PSO2 of the liver and pancreas was the least during hemorrhagic hypotension compared to that with the anesthetics. Because the volative anesthetic-induced hypotension has such a different effect on splanchnic tissue oxygenation compared with hemorrhagic-induced hypotension, the authors conclude that the method of inducing hypotension may have different effects on oxygenation of various tissues.

Anesthetics↗

PubMed2003

Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration.

UNLABELLED: Several reports suggest that clinically used concentrations of inhaled anesthetics can increase conductance through noninactivating potassium channels and that the resulting hyperpolarization might decrease excitability, thereby leading to the anesthetic state. We speculated that animals deficient in such potassium channels might be resistant to the effects of anesthetics. Thus, in the present study, we measured the minimum alveolar anesthetic concentration (MAC) needed to prevent movement in response to a noxious stimulus in 50% of adult mice lacking functional KCNK5 potassium channel subunits and compared these results with those for heterozygous and wild-type mice. We also measured MAC in weaver mice that had a mutation in the potassium channel Kir3.2 and compared the resulting values with those for wild-type mice. MAC values for desflurane, halothane, and isoflurane for KCNK5-deficient mice and isoflurane MAC values for weaver mice did not differ from MAC values found in control mice. Our results do not support the notion that these potassium channels mediate the capacity of inhaled anesthetics to produce immobility. In addition, we found that the weaver mice did not differ from control mice in their susceptibility to convulsions from the nonimmobilizers flurothyl [di-(2,2,2,-trifluoroethyl)ether] or 2N (1,2-dichlorohexafluorocyclobutane). IMPLICATIONS: Mice harboring mutations in either of two different potassium channels have minimum alveolar anesthetic concentration (MAC) values that do not differ from MAC values found in control mice. Such findings do not support the notion that these potassium channels mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation.

Anesthetics, Inhalation↗

PubMed2003

Alpha-2 adrenoreceptors probably do not mediate the immobility produced by inhaled anesthetics.

UNLABELLED: Agonism of alpha-adrenoreceptors has a powerful anesthetic result mediated, in part, by effects on the spinal cord. Alpha-adrenoreceptor agonists (e.g., dexmedetomidine) can decrease the minimum alveolar anesthetic concentration (MAC) of inhaled anesthetics (e.g., halothane) to zero, with an apparently additive interaction between halothane and dexmedetomidine. We tested whether the capacity of the inhaled anesthetic isoflurane to produce immobility in the face of noxious stimulation resulted from agonism of alpha-adrenoreceptors. MAC (the concentration required to eliminate movement in response to a noxious stimulus in 50% of subjects) of isoflurane was determined before and after intraperitoneal administration of the alpha-adrenoreceptor antagonists yohimbine and atipamezole. The doses of yohimbine and atipamezole equaled or exceeded those that reverse the ability of agonism of alpha-adrenoreceptors to decrease MAC. Smaller doses of yohimbine or atipamezole slightly increased (by 10%) the MAC of isoflurane, an increase we interpret as the result of blockade of a small amount of tonically active alpha-adrenoreceptor activity. Doses five-fold larger did not change MAC. Doses 10-fold larger decreased MAC. We conclude that alpha-adrenoreceptors do not or minimally mediate the capacity of inhaled anesthetics to produce immobility. IMPLICATIONS: Although stimulation (agonism) of alpha-2 adrenoreceptors can decrease the inhaled anesthetic concentration required to produce immobility in the face of noxious stimulation, blockade of alpha-2 adrenoreceptors minimally affects the concentration. Thus, augmentation of the effect of alpha-2 adrenoreceptors is not an appreciable part of the mechanism whereby inhaled anesthetics produce immobility.

Adrenergic alpha-Antagonists↗

PubMed2004

Derivation of preliminary three-dimensional pharmacophores for nonhalogenated volatile anesthetics.

We investigated the molecular basis for the immobilizing activity of nonhalogenated volatile anesthetics by using comparative molecular field analysis (CoMFA). In vivo potency data (expressed as minimum alveolar anesthetic concentrations) for 38 structurally diverse drugs were obtained from the literature. The anesthetics were randomly divided into a training-set (n = 28) used to formulate the activity models and a test-set (n = 10) used to independently assess the models' predictive power. The anesthetic structures were aligned to maximize their similarity in molecular shape and electrostatic potential to conformers of the most active drug in the group: hexanol. The individual conformers and alignments with maximum similarity (calculated with combined Carbo indices) were retained and used to derive the CoMFA activity models. The final CoMFA model explained 95.5% of the variance in the observed activities of the training-set anesthetics. The model had good predictive capability for both the training-set drugs (cross-validated r(2) = 0.824) and the randomly excluded test-set anesthetics (r(2) = 0.921). Pharmacophoric maps were derived by identifying the spatial distribution of key areas in which steric and electrostatic interactions are important in determining the immobilizing activity of the anesthetics considered.

Anesthetics, Inhalation↗

PubMed2006

Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics.

N-Methyl-d-aspartate (NMDA) receptors have a presumed role in excitatory synaptic transmission and nociceptive pathways. Although previous studies have found that inhaled anesthetics inhibit NMDA receptor-mediated currents at clinically relevant concentrations, the use of different experimental protocols, receptor subtypes, and/or tissue sources confounds quantitative comparisons of the NMDA receptor inhibitory potencies of inhaled anesthetics. In the present study, we sought to fill this void by defining, using the two-electrode voltage-clamp technique, the extent to which diverse clinical and aromatic inhaled anesthetics inhibit the NR1/NR2B subtype of the human NMDA receptor expressed in Xenopus laevis oocytes. At 1 minimum alveolar anesthetic concentration (MAC), anesthetic compounds reversibly inhibited NMDA receptor currents by 12 +/- 6% to 74 +/- 6%. These results demonstrate that equianesthetic concentrations of inhaled anesthetics can differ considerably in the extent to which they inhibit NMDA receptors. Such differences may be useful for defining the role that this receptor plays in producing the in vivo actions of general anesthetics.

Anesthetics, General↗

PubMed2007

AnaConDa reflection filter: bench and patient evaluation of safety and volatile anesthetic conservation.

BACKGROUND: The AnaConDa filter permits administration of volatile anesthetic without the use of an anesthesia machine. It is intended for use in the intensive care unit. METHODS: We studied the AnaConDa reflection filter on the bench and in anesthetized patients. The bench analysis used a test lung, a gas analyzer, an intensive care ventilator, the AnaConDa filter, and a syringe pump. We studied a range of tidal volume, respiratory rate, and positive end-expiratory pressure values. We simulated errors during syringe refilling and patient transportation. In 15 anesthetized patients, we used the AnaConDa with constant ventilation variables, a constant sevoflurane infusion rate (4-5 mL/h), and two consecutive fresh gas flow levels. RESULTS: In the bench study, the expired volatile anesthetic fraction decreased linearly with respiratory frequency at constant minute ventilation, and decreased markedly in a hyperbolical manner when tidal volume increased at a constant respiratory rate. Changing the positive end-expiratory pressure level and inspiration/expiration ratio did not modify the AnaConDa's performance. Several safety failures were observed: refilling caused a transient change in AnaConDa output because of a pumping effect, and a standard Luer lock made it possible to connect the halogenate syringe on an IV infusion line. In anesthetized patients, reducing fresh gas flow from 8 to 1 L/min led to a median 40% increase in the expired volatile anesthetic fraction. CONCLUSIONS: This study shows that the device is generally reliable, but that there are several conditions under which it might deliver more anesthetic than intended.

Anesthetics, Inhalation↗

PubMed1997

[Clinical study of patients with positive reactions in patch tests with local anesthetics].

Local anesthetics have been contained in various OTC drugs and the number of cases of allergic contact dermatitis due to local anesthetics has increased recently. Thirty-five hundreds and fourteen cases suspected of suffering from drug eruption or contact dermatitis were the subjects of this study during the 8 years from January, 1988 to December, 1995. One hundred and thirty-eight cases, suspected of having allergic contact dermatitis were patch tested with topical medicaments including local anesthetics and 70 (50.7%) of them showed positive. In 49 of the 60 cases who reacted positively to anesthetics extensive patch tests with the individual ingredients of the products were carried out. The local anesthetics causing positive reactions were as follows (in order of frequency): dibucaine hydrochloride (35 cases: 71.4%), ethyl aminobenzoate (12 cases: 24.5%), lidocaine hydrochloride (2 cases: 4.1%), and procaine hydrochloride (1 case: 2.0%). The number of patients displaying allergies to local anesthetics has increased, especially cases caused by dibucaine hydrochloride. And the total positive reaction rate to dibucaine hydrochloride in the patch tests was 3.7%, which was as high that to the well-known strong sensitizer PPDA (3.9%) and neomycin (2.9%). Forty-three cases sensitive to local anesthetics were also studied for cross-sensitivity.

Anesthetics, Local↗

PubMed1980

Occupational disease in dentistry and chronic exposure to trace anesthetic gases.

A mail survey of 30,650 dentists and 30,547 chairside assistants grouped according to occupational exposure to inhalation anesthetic and sedatives in the dental operatory indicated increased general health problems and reproductive difficulties among respondents exposed to anesthetics. For male dentists who were heavily exposed to anesthetics, the increase in liver disease was 1.7-fold, kidney disease was 1.2-fold, and neurological disease was 1.9-fold. For wives of male dentists who were heavily exposed to anesthetics, the increase in spontaneous abortion rate was 1.5-fold. Among female chairside assistants who were heavily exposed to anesthetics, the increase in liver disease was 1.6-fold, kidney disease was 1.7-fold, and neurological disease was 2.8-fold. The increase in spontaneous abortion rate among assistants who were heavily exposed was 2.3-fold. Cancer rates in women heavily exposed to inhalation anesthetics were increased 1.5-fold but this finding was not statistically significant (P = .06). Separate analysis of the data for disease rates and birth difficulties by type of inhalation anesthetic indicates that in both dentists and chairside assistants chronic exposure to nitrous oxide alone is associated with an increase rate of adverse response.

Abnormalities, Drug-Induced↗

PubMed2002

Studies on target genes of general anesthetics.

Generally speaking, we cannot fully understand the mechanisms of general anesthesia until the molecular mechanisms of consciousness are fully elucidated. Loss of consciousness induced by general anesthetics might involve sensation, motor activity, behavior, memory and self-consciousness. The effects of many anesthetics are not limited to humans but also extend to the animals. Similar levels of minimum anesthetic concentrations are required to induce anesthesia in animals and human, i.e., the minimum alveolar concentration (MAC). Such similarity probably reflects identical anesthetic target molecules and functional conservation based on gene conservation. Thus, to study the mechanisms of anesthetic action, various animal models that are accessible to genetic manipulation, such as nematodes (Caenorhabditis elegans), fruit flies (Drosophila) and mice can be used. Genetic techniques allow for the rapid identification and characterization of genes involved in the actions of general anesthetics. In this review, I will describe the genetic mutations and putative target genes of general anesthetics.

Anesthetics, General↗

PubMed1995

Localization of specific joint causing hindfoot pain: value of injecting local anesthetics into individual joints during arthrography.

OBJECTIVE: The purpose of this study was to evaluate the utility of selective injection of local anesthetic into hindfoot articulations for localizing the source of posttraumatic pain and to compare clinical response with the severity of degenerative change in the various articulations evident on plain radiographs or CT scans. SUBJECTS AND METHODS: Anesthetic arthrography was performed in 18 patients with posttraumatic hindfoot pain. In all, 32 joints were assessed: 15 talocalcaneonavicular, 11 subtalar, five ankle, and one calcaneocuboid. Following intraarticular injection of a mixture of equal amounts of meglumine diatrizoate 60%, lidocaine 1%, and bupivacaine 0.25%, patients were asked to grade the degree of pain relief they experienced on a scale from 0% to 100%. The degree of degenerative changes seen on preliminary radiographs and CT scans was graded blindly and retrospectively by an experienced musculoskeletal radiologist using a 3-point scale (grade 0 indicated a normal joint, grade 1 indicated mild to moderate degenerative change, and grade 2 indicated severe degenerative change). The value of findings on both routine radiographs and CT scans as predictors of the degree of symptomatic relief obtained from specific joint injections was determined. Arthrodesis was performed in nine patients on the basis of the results of anesthetic injections. RESULTS: The degree of pain relief experienced after intraarticular injection of anesthetic correlated with the severity of degenerative change as assessed by routine radiography in 15 of 32 joints and as assessed by CT in eight of 18 joints. In 14 of 32 joints assessed by routine radiography and in seven of 18 joints assessed by CT, the amount of pain relief achieved by anesthetic arthrography was less than that predicted by imaging evidence of degenerative disease. In five of 32 joints judged normal on plain film radiographs, significant pain relief was experienced following anesthetic injection, resulting in a change in the proposed surgical procedure. Long-term follow-up indicated satisfactory results in eight of the nine patients in whom arthrodesis was performed. CONCLUSION: Selective intraarticular anesthetic injections afford a direct method of confirming the site of hindfoot pain and may aid in surgical planning, because plain film radiography or CT may underestimate or poorly indicate the most symptomatic articulations.

Adult↗

PubMed2001

Respiratory reflexes in spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane, isoflurane, or halothane.

OBJECTIVE: To characterize respiratory reflexes elicited by nasal administration of sevoflurane (Sevo), isoflurane (Iso), or halothane (Hal) in anesthetized dogs. ANIMALS: 8 healthy Beagles. PROCEDURE: A permanent tracheostomy was created in each dog. Two to 3 weeks later, dogs were anesthetized by IV administration of thiopental and alpha-chloralose. Nasal passages were isolated such that inhalant anesthetics could be administered to the nasal passages while the dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of each anesthetic at 1.2 and 2.4 times the minimum alveolar concentration (MAC) and the full vaporizer setting (5%) were recorded. Reflexes in response to administration of 5% of each anesthetic also were recorded following administration of lidocaine to the nasal passages. RESULTS: Nasal administration of Sevo, Iso, and Hal induced an immediate ventilatory response characterized by a dose-dependent increase in expiratory time and a resulting decrease in expired volume per unit of time. All anesthetics had a significant effect, but for Sevo, the changes were smaller in magnitude. Responses to administration of each anesthetic were attenuated by administration of lidocaine to the nasal passages. CONCLUSIONS AND CLINICAL RELEVANCE: Nasal administration of Sevo at concentrations generally used for mask induction of anesthesia induced milder reflex inhibition of breathing, presumably via afferent neurons in the nasal passages, than that of Iso or Hal. Respiratory reflexes attributable to stimulation of the nasal passages may contribute to speed of onset and could promote a smoother induction with Sevo, compared with Iso or Hal.

Administration, Intranasal↗

PubMed1995

Mutations that affect ion channels change the sensitivity of Drosophila melanogaster to volatile anesthetics.

We have quantitated the response of D. melanogaster to general anesthetics with a device, the inebriometer, that assays the fly's geotactic and postural behavior. When alleles of several loci that encode or regulate subunits of ion channels were compared with control stocks, several ion channel mutants clearly increased the anesthetic sensitivity of Drosophila. The effects were specific in that: a) for several alleles, genetic tests indicated that the anesthesia phenotype was due to the ion channel mutation and not to extraneous genetic differences between the stocks; b) a given ion channel mutation often affected the response to one anesthetic but not another; and c) the behavior of decapitated flies in the inebriometer indicated that the anesthetic phenotype of several mutants did not merely reflect a global change in the fly's physiology. These results provide support for the idea that ion channels are on the pathway(s) influenced by anesthetics and that different anesthetics use different pathways. They also provide perspective on the behavior of previously isolated mutations (har) that decrease the sensitivity of Drosophila to anesthetics in the inebriometer.

Anesthetics, Inhalation↗

PubMed1991

Inhibitory effects of local anesthetics on migration, extracellular release of lysosomal enzyme, and superoxide anion production in human polymorphonuclear leukocytes.

This study examined the effects of four typical local anesthetics, lidocaine, prilocaine, procaine and tetracaine, on the functioning of human polymorphonuclear leukocytes (PMN). PMN were stimulated by fMet-Leu-Phe (FMLP) or phorbol myristate acetate (PMA) to elicit chemotaxis, extracellular release of beta-glucuronidase (BGL) and superoxide anion (SOA) production. The four agents inhibited chemotaxis efficiently and in a concentration-dependent manner but had only weak effects on the release of BGL. The effect of tetracaine was strongest, followed by lidocaine, then prilocaine, whereas the effect of procaine was blunt. The 50% inhibitory concentrations (IC50 in molarity) of the four local anesthetics for chemotaxis were as follows: tetracaine = 4.1 x 10(-4), lidocaine = 3.2 x 10(-3), prilocaine = 3.6 x 10(-3), procaine = 4.9 x 10(-3), those for SOA production induced by FMLP were: tetracaine = 3.1 x 10(-4), lidocaine = 5.9 x 10(-3), prilocaine = 1.9 x 10(-2), procaine = 1.2 x 10(-2), those for SOA production induced by PMA were: tetracaine = 1.1 x 10(-3), lidocaine = 1.2 x 10(-2), prilocaine = 1.5 x 10(-2), procaine = 2.5 x 10(-2), and those for release of BGL were: tetracaine = 1.6 x 10(-3), lidocaine = 5.3 x 10(-3), prilocaine = 2.8 x 10(-2), procaine = 1.2 x 10(-1). The IC50 seemed to relate to the anesthetic's chemical structures and their inhibitory properties on PMN functions, as lidocaine and prilocaine, which are aminoamide type anesthetics, preferentially inhibited chemotaxis, whereas tetracaine and procaine, aminoester type anesthetics, inhibited SOA production induced by FMLP. The results suggest that the inhibitory effects of local anesthetics on human PMN functions are also correlated with local anesthetic potency and vary according to differences in their chemical structures.

Anesthetics, Local↗

PubMed2000

Genetic effects on an anesthetic-sensitive pathway in the brain of Drosophila.

General anesthetics are known to inhibit the electrically induced escape response of the fruitfly through action within the brain. We examined this response and its sensitivity to anesthetics in several mutants that cause significant disruption of the mushroom body and other structures of the central brain in adult flies. Because we show here that anesthesia sensitivity is influenced by genetic background, we have used a set of congenic mutant lines. Sensitivity to halothane is normal in most of these lines, indicating that the anesthetic target is unaffected by the gross status of the central brain. Thus, for the escape response, anesthetic sensitivity is not a global feature but reflects action at a localized target. Only the mushroom body defect (mud) line showed an increased sensitivity of the escape response to halothane. Sensitivity to two other anesthetics is also perturbed in this line, albeit less dramatically so. The behavior of mud/+ heterozygotes and the comparison of brain anatomy among all the mutant lines imply that the effect of the mud mutation on anesthesia is not via gross alteration of central brain structures. The possibility that an adventitious mutation in the mud line is responsible for the effects on anesthesia is disfavored by the behavior of a heterozygote between two mud alleles. Although we do not yet know whether the mud gene encodes an anesthetic target or influences the functioning of an anesthetic-sensitive neuron in this pathway, our work indicates that this gene regulates the effects of halothane on a circumscribed pathway.

Anesthetics, Inhalation↗

PubMed2000

The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics.

Despite widespread use of volatile general anesthetics for well over a century, the mechanisms by which they alter specific CNS functions remain unclear. Here, we present evidence implicating the two-pore domain, pH-sensitive TASK-1 channel as a target for specific, clinically important anesthetic effects in mammalian neurons. In rat somatic motoneurons and locus coeruleus cells, two populations of neurons that express TASK-1 mRNA, inhalation anesthetics activated a neuronal K(+) conductance, causing membrane hyperpolarization and suppressing action potential discharge. These membrane effects occurred at clinically relevant anesthetic levels, with precisely the steep concentration dependence expected for anesthetic effects of these compounds. The native neuronal K(+) current displayed voltage- and time-dependent properties that were identical to those mediated by the open-rectifier TASK-1 channel. Moreover, the neuronal K(+) channel and heterologously expressed TASK-1 were similarly modulated by extracellular pH. The decreased cellular excitability associated with TASK-1 activation in these cell groups probably accounts for specific CNS effects of anesthetics: in motoneurons, it likely contributes to anesthetic-induced immobilization, whereas in the locus coeruleus, it may support analgesic and hypnotic actions attributed to inhibition of those neurons.

Action Potentials↗

PubMed2001

[Efficiency of bispectral index in anesthetic management of a patient with hypothyroidism].

A 72-year-old, female patient with severe hypothyroidism underwent tracheostomy using deltopectral flap. During the anesthetic management, we assessed the hypnotic level using the bispectral index and regulated the dose of general anesthetics to maintain the bispectral index at about 50. The general anesthetics caused a marked cardiovascular depression, but the condition was treatable with the intravenous administration of dopamine. Using these methods, we could anesthetize this patient safely without a prolonged awakening time from general anesthesia. Although the anesthetic requirement for patients with hypothyroidism is generally thought to be decreased, there is no practical index by which we can estimate the optimal dose of anesthetic agents for these patients. This case report shows that the assessment of the hypnotic level by the bispectral index can be utilized as an efficient index to determine the optimal dose of general anesthetics for patients with hypothyroidism.

Aged↗