Action Of Inhalational Anesthetics Research Articles

The role of astrocytic γ-aminobutyric acid in the action of inhalational anesthetics

BackgroundInhalational anesthetics target the inhibitory extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. Both neuronal and glial GABA mediate tonic inhibition of the extrasynaptic GABAA receptors. However, the role of glial GABA during inhalational anesthesia remains unclear. This study aimed to evaluate whether astrocytic GABA contributes to the action of different inhalational anesthetics. MethodsGene knockout of monoamine oxidase B (MAOB) was used to reduce astrocytic GABA levels in mice. The hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane were assessed by evaluating the loss of righting reflex (LORR) and tail-pinch withdrawal response (LTWR) in MAOB knockout and wild-type mice. Minimum alveolar concentration (MAC) for LORR, time to LORR, MAC for LTWR and time to LTWR of isoflurane, sevoflurane, and desflurane were assessed. ResultsTime to LORR and time to LTWR with isoflurane were significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001 and P = 0.032, respectively). Time to LORR with 0.8 MAC of sevoflurane was significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001), but not with 1.0 MAC of sevoflurane (P=0.217). MAC for LTWR was significantly higher in MAOB knockout mice exposed to sevoflurane (P < 0.001). With desflurane, MAOB knockout mice had a significantly higher MAC for LORR (P = 0.003) and higher MAC for LTWR (P < 0.001) than wild-type mice. ConclusionsMAOB knockout mice showed reduced sensitivity to the hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane. Behavioral tests revealed that the hypnotic and immobilizing effects of inhalational anesthetics would be mediated by astrocytic GABA.

Bioelectric activity monitoring of the hippocampal complex: action of inhalation anesthetics as a functional sample

Monitoring of the bioelectric activity of the hippocampal complex is performed according to the indications of patients with pharmacoresistant mesial temporal lobe epilepsy, who are indicated for surgical removal of the epileptic focus. The work was aimed at comparing the dynamics of the amplitude-frequency parameters of the bioelectrical activity of the hippocampal complex under the action of general anesthetics by comparing the parameters recorded before surgery and intraoperatively. The study included 8 patients with mesial temporal lobe epilepsy who, within the framework of pre-surgical planning, underwent invasive monitoring of the bioelectrical activity of the cortex and hippocampal com- plex, and then underwent surgical resection of the epileptic focus under general anesthesia with sevoflurane. Registration of 12 hippocampal tracks was carried out in dynamics: during extraoperative and intraoperative neurophysiological monitoring. In the state of calm wakefulness, the pattern of bioelectric activity of the hippocampal complex without structural changes was formed mainly by the activity of the alpha and theta frequency ranges. Under general anesthesia with sevoflurane, a slow-wave delta-range activity was recorded on the intraoperative ES- ubCoG. When the hippocampal complex was involved in the epileptic system, its activity in the state of passive wakefulness was represented by the slow-wave frequency range. Under the conditions of inhalation anesthesia with sevoflurane, the proportion of delta activity significantly decreased, and a state of dysrhythmia was observed without a clear dominance of activity in any range.

Gap junctions may participate in the mechanism of action of inhalational anesthetics

Background Inhalational anesthetics have been widely used in clinical anesthesia for a wide range of surgeries.But the mechanism of anesthetic actions is still not clear.Gap junctions (GJ) are important ways of information delivery among mediate cells in nervous system.Perhaps it is one of the molecular sites of inhalational anesthetic action.Objective The purpose of this article is to investigate whether GJ and GJ mediated intercellular communication may participate in the mechanism of action of inhalational anesthetics or not.Content The mechanism of action of inhalational anesthetics has been analyzed.Moreover,the structure,distribution and function of GJ and its relationship with inhalational anesthetics in the central nervous system were also described.Trend The research about GJ and the intercellular communication mediated by GJ is a new direction to explore the anesthetic mechanism. Key words: Gap junction; Inhalational anesthetics; Mechanism of action

Complex formation of skeletal muscle Ca 2+-regulatory membrane proteins by halothane

In skeletal muscle, halothane affects the functions of several Ca 2+-regulatory membrane proteins involved in the excitation–contraction–relaxation cycle. To investigate the mechanism by which this volatile anesthetic interferes with Ca 2+-homeostasis, we studied potential changes in protein–protein interactions by halothane. Using comparative immunoblotting of microsomal muscle proteins separated on native and denaturing gels, we show here that halothane induces oligomerization of the terminal cisternae Ca 2+-binding protein calsequestrin, the junctional ryanodine receptor Ca 2+-release channel and the transverse-tubular α 1-dihydropyridine receptor. This agrees with previous reports on the modulation of Ca 2+-release activity by halothane since interactions between the voltage-sensing α 1-dihydropyridine receptor, the ryanodine receptor and the luminal Ca 2+-reservoir might result in a rapid release of Ca 2+-ions. Furthermore, this study supports the idea that specific protein sites are involved in the action of inhalational anesthetics and that halothane might trigger abnormal Ca 2+-homeostasis in malignant hyperthermia via oligomerization of the mutated ryanodine receptor.

Stable Inhibition of Brain Synaptic Plasma Membrane Calcium ATPase in Rats Anesthetized with Halothane

The authors recently showed that plasma membrane Ca(2+)-ATPase (PMCA) activity in cerebral synaptic plasma membrane (SPM) is diminished in a dose-related fashion during exposure in vitro to halothane, isoflurane, xenon, and nitrous oxide at clinically relevant partial pressures. They have now extended their work to in vivo studies, examining PMCA pumping in SPM obtained from control rats decapitated without anesthetic exposure, from rats decapitated during halothane anesthesia, and from rats decapitated after recovery from halothane anesthesia. Three treatment groups were studied: 1) C, control rats that were decapitated without anesthetic exposure, 2) A, anesthetized rats exposed to 1 minimum effective dose (MED) for 20 min and then decapitated, and 3) R, rats exposed to 1 MED for 20 min and then decapitated after recovery from anesthesia, defined as beginning to groom. Plasma membrane Ca(2+)-ATPase pumping and Ca(2+)-dependent ATPase hydrolytic activity, as well as sodium-calcium exchanger activity and Na+-K+-ATPase hydrolytic activity, were assessed in cerebral SPM. In addition, halothane effect on smooth endoplasmic reticulum Ca(2+)-ATPase (SERCA) was examined. Plasma membrane Ca(2+)-ATPase transport of Ca2+ into SPM vesicles from anesthetized rats was reduced to 71% of control (P < 0.01) compared with 113% of control for the recovered group (NS). No depression by halothane of SERCA activity, sodium-calcium exchanger, or Na+-K+-ATPase activity was noted among the CAR treatment groups. Plasma membrane Ca(2+)-ATPase is selectively and stably inhibited in cerebral SPM from rats killed while anesthetized with halothane, compared with rats killed without anesthesia or after recovery from anesthesia. The studies described in this report, in conjunction with previously reported inhibition of PMCA activity in vitro by a wide range of anesthetic agents, indicate a relationship between inhibition of PMCA and action of inhalational anesthetics.

Interaction of trichloroethylene with phosphatidylcholine and its localization in the phosphatidylcholine vesicles: a 1H-NMR study

The interaction of trichloroethylene, an inhalation general anesthetic, with egg yolk phosphatidylcholine (EYPC) and its localization in small unilamellar vesicles (SUV) has been studied by Nuclear Magnetic Resonance. These studies demonstrate that inhalation anesthetic can interact nonspecifically with lipid molecules. Furthermore, it suggests that the action of inhalation anesthetics is directed primarily to the interfacial region of the lipid membrane.

Giant planar lipid bilayer: I. Capacitance and its biphasic response to inhalation anesthetics

A giant sized lipid bilayer (about 200 mm 2 with prolonged lifetime (24 hr) was prepared from oleylamine. From the capacitance of the membrane, the thickness of the bilayer was estimated to be 3.4 nm. Three inhalation anesthetics—chloroform, halothane, and enflurane—increased the capacitance in two distinctly different modes. At low concentrations, the anesthetics increased the capacitance asymptotically to a limiting value. Further increase of the anesthetic concentration resulted in a sudden increase in capacitance with a break in the anesthetic concentration-capacitance curves. The following model is proposed for the interaction of anesthetics with lipid bilayers: at low concentrations below the breaking point, the anesthetics are mainly adsorbed to the interface. At the breaking point, they saturate the bilayer surface. Above this concentration, they start to penetrate into the lipid core. The partial pressures of anesthetics at the surface-saturating level correlated to the clinical potency with a correlation coefficient of better than 0.93. The thickness of the lipid core was reduced 3.2 nm at the breaking point. The decrement was 5.9%. Because the relative electrical permittivity of anesthetics is higher than that of the membrane lipid, the penetration may result in an increase of the relative permittivity of the bilayer. The sudden increase of capacitance at high anesthetics concentrations presumably is caused by this mechanism. The partition coefficients of the anesthetics between the bilayer and water were estimated to be as follows: at concentrations below the breaking point, chloroform 2660, halothane 3990, and enflurane 2750; and at concentrations above the breaking point, chloroform 1980, halothane 5720, and enflurane 2700. The good correlation between the partial pressures of the anesthetics to saturate the bilayer surface area and those of the clinical potencies suggests that (1) the action of inhalation anesthetics is nonspecific, and (2) physical properties of the nonphysiological simple bilayer can be used to probe physiological actions of these drugs on membranes, although they may represent a part of the drug actions.

Intravenous anesthesia in oral surgery

T HE two discoveries which probably aided modern surgery the most are the germ theory of disease and the discovery of sulfuric ether as an anesthetic agent. I shall not dwell on the history of inhalation anesthetics, such as ether and nitrous oxide, since every student of the history of dentistry knows the names of Wells and Morton and the r61e dentistry has played in developing these anesthetic agents. I should, however, like to discuss for a few minutes the physiologic action of inhalation anesthetics. According to Cohen-Githens, they may be divided into two classes: (1) the volatile agents including chloroform, ether, ethyl chloride, et cetera, and (2) the gaseous ones such as nitrous oxide, ethylene, and cyclopropane. Those of the first group are inhaled in relatively small amounts in the atmospheric air and derive their narcotic effect from a. chemical action on the nerve cells. Those of the second group are inhaled in much greater concentration, 85 to 95 per cent mixed with but 5 to 15 per cent oxygen. In such concentration they greatly interfere with normal tissue oxidation and are thought to produce anesthesia by asphyxiation of the higher nerve centers. Nevertheless any of the agents in either group when properly administered to patients in whom there are no contraindications for their use, are very satisfactory anesthetics. Because of the frequent contraindications to their use and the expense and training necessary for their safe administration, a third type of anesthesia appeared ; namely, the local anesthetics. Keller’ in 1884 demonstrated the use of cocaine as a local anesthetic. Since then efforts have been made to improve its use along three main lines: (1) to increase the topical effect of the drug, (2) to seek substances safer and less toxic than cocaine, (3) to perfect the manner of its administration. You are all aware of the improvements made in local anesthesia, both in the drugs themselves and in the various techniques of their application. A fourth type of anesthesia has now become available which we will call intravenous anesthesia. This type of anesthesia has long been used in experimental work. It was used in Europe on human patients long before it was taken up in this country. Curiously enough it embraces in part the qualities of both the other types: in that it is a general anesthetic, one whi’ch produces complete narcosis, and in that it is administered in the same fashion as a local anesthetic, by injection, I shall limit my remarks to the use of evipal soluble (Winthrop), a trade name given this particular barbiturate by the manufacturer. There are other similar products on the market equally good. Intravenous evipal soluble is not new in the true sense of the word but is the result of the attempt of research workers to find a quick acting, safe, intravenous anesthetic which also would have a fast recovery. Evipal is a barbituric