RELATION OF NEUROLOGICAL COMPLICATIONS OF SUBARACHNOID BLOCK TO SOME UNSEEN DANGERS OF NEW TECHNIQUES

Sterilizing solutions that by accident become mixed into the anesthetic agent are probably the etiological factor producing many of the neurological complications following spinal anesthesia.Use of sterilizing solutions having an intensity of color so great that even one drop in the contents of an ampule will definitely color the anesthetic agent is the criterion of safety.     

Population heterogeneity and color stimulus heterogeneity in agent-based color categorization

Investigating the interactions between universal and culturally specific influences on color categorization across individuals and cultures has proven to be a challenge for human color categorization and naming research. The present article simulates the evolution of color lexicons to evaluate the role of two realistic constraints found in the human phenomenon: (i) heterogeneous observer populations and (ii) heterogeneous color stimuli. Such constraints, idealized and implemented as agent categorization and communication games, produce interesting and unexpected consequences for stable categorization solutions evolved and shared by agent populations. We find that the presence of a small fraction of color deficient agents in a population, or the presence of a “region of increased salience” in the color stimulus space, break rotational symmetry in population categorization solutions, and confine color category boundaries to a subset of available locations. Further, these heterogeneities, each in a different, predictable, way, might lead to a change of category number and size. In addition, the concurrent presence of both types of heterogeneity gives rise to novel constrained solutions which optimize the success rate of categorization and communication games. Implications of these agent-based results for psychological theories of color categorization and the evolution of color naming systems in human societies are discussed.     

Selecting anesthetic agents for human safety and animal recovery surgery

This review provides information to scientists performing animal surgery with recommendations for choosing an appropriate anesthetic agent. The human health risks from exposure to various anesthetic agents as well as methods to minimize exposure are discussed. In brief, methoxyflurane, used with precautions, is recommended for rodent bench-top surgery. When a precision vaporizer is available, isoflurane is usually the agent of choice. Other agents, including injectables, are considered.     

Manipulating the Papanicolaou staining method. Role of acidity in the EA counterstain

The role of phosphotungstic acid as the main pH-controlling agent in Papanicolaou's EA stain was analyzed, including its effect on the competition between eosin Y and light green, the principal components of EA solutions, and this acid was compared with HCl as an acidifying agent. The amount of phosphotungstic acid in the solution determined the color of the cytoplasm. Our study led to a better understanding and a simplification of the staining procedure. With the acquired knowledge, the Papanicolaou counterstain can be standardized to suit the taste of the individual cytologist and can add to the predictability of the results.     

Effect of anesthetic agents on lavage fluid parameters used as indicators of pulmonary injury

The effect of the anesthetic agent used in killing animals in an in vivo pulmonary toxicity screening test was examined in Fischer-344 rats and in Syrian hamsters. Using animals killed by cervical dislocation with no anesthesia as a baseline, two types of anesthetic agents (halothane, sodium pentobarbital) and carbon dioxide were tested. Carbon dioxide caused the greatest perturbance of baseline lavage fluid and tissue parameters normally used in the screening test. Halothane anesthesia caused the least perturbance in the screening test parameters and was selected as the anesthetic of choice for use in future pulmonary toxicity tests.     

Determinants of the anesthetic sensitivity of neuronal nicotinic acetylcholine receptors.

Some neurotransmitter-gated ion channels are very much more sensitive to general anesthetics than others, even when they are genetically and structurally related. The most striking example of this is the extreme sensitivity of heteromeric neuronal nicotinic acetylcholine receptors to inhalational general anesthetics compared with the marked insensitivity of the closely related homomeric neuronal nicotinic receptors. Here we investigate the role of the alpha subunit in determining the anesthetic sensitivity of these receptors by using alpha(3)/alpha(7) chimeric subunits that are able to form functional homomeric receptors. By comparing the sensitivities of a number of chimeras to the inhalational agent halothane we show that the short (13 amino acids) putative extracellular loop connecting the second and third transmembrane segments is a critical determinant of anesthetic sensitivity. In addition, using site-directed mutagenesis, we show that two particular amino acids in this loop play a dominant role. When mutations are made in this loop, there is a good correlation between increasing anesthetic sensitivity and decreasing acetylcholine sensitivity. We conclude that this extracellular loop probably does not participate directly in anesthetic binding, but rather determines receptor sensitivity indirectly by playing a critical role in transducing anesthetic binding into an effect on channel gating.     

Juvenile Rats Show Altered Gut Microbiota After Exposure to Isoflurane as Neonates

Neurochemical Research - Inhaled anesthetic agents may be neurotoxic to the developing brain of a neonatal rodent. Isoflurane is a commonly used volatile anesthetic agent for maintenance of general...     

Alpha-chloralose suppression of neuronal activity

Alpha-chloralose, an anesthetic agent widely used in neurophysiologic studies, caused a significant and long-lasting suppression of single neuron activity recorded from two areas of the central nervous system in decerebrate cats. A 50 mg/kg dose (an average anesthetic dose used in many neurophysiologic studies) caused suppression of spontaneous and evoked activity of neurons in the dorsal horn of the spinal cord and greater suppression of neurons in the nucleus reticularis gigantocellularis (NRGC) of the medial medullary reticular formation. Many researchers are of the opinion that alpha-chloralose causes less suppression of the central nervous system (CNS) than other commonly used anesthetic agents. The neuronal suppression recorded in this study appears similar in many ways to suppression caused by other anesthetic agents in the same two areas of the CNS. The results of the present study suggest that alpha-chloralose may be capable of producing significant suppression of neurons in the dorsal horn of the spinal cord and NRGC. Its ability to influence other areas of the CNS should not be inferred from these results, but the data do indicate the importance of evaluating the effects of anesthetics upon neurophysiologic systems under study.     

Changes in Effective Connectivity by Propofol Sedation

Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent. Functional connectivity does not provide information of directional changes in the dynamics observed during unconsciousness. The aim of the present study was to investigate, in healthy humans during an auditory task, the changes in effective connectivity resulting from propofol induced loss of consciousness. We used Dynamic Causal Modeling for fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic agent in the auditory system. Our results suggest that the dynamic observed in the auditory system during unconsciousness induced by propofol, can result in a mixture of two effects: a local inhibitory connectivity increase and a decrease in the effective connectivity in sensory cortices.     

SYSTEMIC TOXIC REACTIONS TO LOCAL ANESTHETICS

The topical use of anesthetic agents involves an element of risk. Systemic toxic reactions are rare, but they do occur and may result in death. When a reaction occurs from a topical application, it usually progresses rapidly to respiratory and cardiovascular collapse, and thus therapy must be instituted with more haste to avoid deaths. Fatal systemic toxic reactions from topically administered anesthetic drugs are, in effect, usually not due to well informed use of the drug but to misuse owing to less than complete understanding of absorption.Emphasis is placed on the causes, prophylaxis and treatment of severe systemic toxic reactions which follow the topical application of local anesthetic drugs. If systemic toxic reactions resulting from a safe dose of a local anesthetic agent are correctly treated, there will usually follow an uneventful recovery rather than a catastrophe.     

The membrane volume occupied by anesthetic molecules: A reinterpretation of the erythrocyte expansion data

Seeman and coworkers (Seeman, P. (1972) Pharmacol. Rev. 24, 583–655) calculated that anesthetic agents exapnd membrane volume ten times more than the van der Waals volume of the agent alone. Their calculation was based on the assumption that the thickness of the erythrocyte membrane expands at the same rate as the surface area. However, recent data on bilayer membranes demonstrate that an expansion of membrane surface area is accompanied by a decrease in membrane thickness. A reinterpretation of their erythrocyte area expansion data using an appropriate contraction of membrane thickness suggests the volume in a membrane occupied by anesthetic molecules is approximately equal to their van der Waals volume.     

A core process in receptor function, general anesthesia, sleep, and aging

The diffusion of ligands and proteins was proposed to be guided by chreodes in water organized by protein-surface side chains with varying hydropathic states. These chreodes are proposed to be the target of volatile general anesthetic agents. The similarity between this effect and sleep deprivation leads to a proposal of an external agent responsible for sleep. This agent is elemental nitrogen. An extension of this effect is the concept that elemental nitrogen is a core factor in aging.     

Sedative and hypnotic effects of combined administration of metoclopramide and ketamine in chickens

Metoclopramide is a dopamine receptor antagonist used in animals as both an antiemetic and a gastroprokinetic agent. In chickens, the drug causes central nervous system depression. The authors examined the potential sedative and hypnotic effects of metoclopramide when administered in combination with the anesthetic agent ketamine in 1-3-week-old chicks. Concomitant administration of metoclopramide and ketamine markedly reduced the median effective doses (ED50s) of both drugs for the induction of sedation and sleep in the chicks. The results suggest potential therapeutic applications of the metoclopramide-ketamine combination as a restraining agent in avian species not intended for human consumption.     

Anesthetic Gases and Water Structure : The effect of xenon on tritiated water flux across the gut

Pauling and Miller have independently proposed that the presence of an anesthetic gas in tissue induces a cage-like arrangement of hydrogen-bonded water molecules. The theories recognize that most gas-hydrate crystals would not form at the temperature and pressure that exist during anesthesia and propose that other components of tissue such as protein should have a stabilizing effect. Measurements of the behavior of water, rather than the anesthetic agent, would provide alternative information about the likelihood of hydrate crystal formation and this information could be such as to be applicable to body temperature and to pressures used for anesthesia. If the number of hydrogen-bonded water molecules in tissue is increased, then the movement of an average water molecule should be hindered. Movement of water through the tissue may be measured by tagging it with tritium and the anesthetic gas should then slow the movement of tritiated water through the tissue. The flux of tritiated water through rat cecum is indeed slowed when the cecum is exposed to the anesthetic gas, xenon, which can participate biochemically only by virtue of its van der Waals interaction. The decrement in water flux is in reasonable agreement with what could be expected theoretically from calculations based on the activation energy for the self-diffusion of water and the degree of hypothermia necessary to produce narcosis.     

Hydroxydione sodium (viadril) for anesthesia; a report of clinical experience

Hydroxydione sodium (Viadril(R)) is a new anesthetic agent, derived from a family of chemical compounds not previously associated with anesthetic properties-namely, the steroids. The use of Viadril in sixty operative procedures provided the basis of this communication, which reports the signs of anesthesia and the main pharmacophysiological effects of Viadril as observed clinically.     

Plasma and cerebrospinal fluid concentration of neuropeptide Y, serotonin, and catecholamines in patients under propofol or isoflurane anesthesia

Propofol is a widely used anesthetic for both induction and maintenance of anesthesia during surgery. A strong feeling of hunger has been reported during the early recovery period after propofol anesthesia. We have investigated the effect of propofol on appetite in 10 patients undergoing a craniotomy and in parallel measured neuropeptide Y (NPY), catecholamines, and serotonin levels in the cerebrospinal fluid and plasma during anesthesia. Ten patients anesthetized with a volatile agent (isoflurane) served as a control group. Plasma NPY and catecholamines levels were not affected by surgery at any time. We observed a strong increase in NPY concentrations in the cerebrospinal fluid independently of the anesthetic technique agent used, whereas catecholamines were unchanged. We found that serotonin concentrations decreased significantly in the plasma (but not in the cerebrospinal fluid) of patients treated by propofol when compared with the control group; this decrease was associated with an increase of hunger early postoperatively. We concluded that the proappetite effect of propofol is mediated through a decrease of serotonin at the peripheral level.     

Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly understood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transition of bovine serum albumin. We find that halothane (0.6-10 mM) stabilizes the folded state of this protein, increasing its transition midpoint temperature from 62 to 71 degrees C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the thermally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change DeltaH for unfolding of 170 kcal/mol, the increase from 62 to 71 degrees C corresponds to an additional Gibbs energy of stabilization (DeltaDeltaG) due to halothane of more than 4 kcal/mol. Analysis of the dependence of DeltaDeltaG on halothane concentration shows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concentrations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown to be stabilized by an inhalational anesthetic.     

Water as a complex system: its role in ligand diffusion, general anesthesia, and sleep

The work and inspiration of Robert Rosen is stated and expressed in personal tones. The concept of passages through water (H2O) near protein surfaces is reviewed in terms of its influence on ligand diffusion to an effector. This is offered as a target for interference by a non-specific general anesthetic agent. In view of the similarities between this anesthetic state and sleep, this mechanism is proposed to be operative for the sleep/wake states. Based on this mechanism and other factors, nitrogen (N2) is proposed as an exogenous sleep factor.     

Local anesthetics: stimulation of incorporation of inositol into phosphoinositides in guinea pig cerebral cortical synaptoneurosomes

Various local anesthetics enhanced the incorporation of [3H]inositol into phosphoinositides in guinea pig cerebral cortical synaptoneurosomes. Dibucaine, QX-572 and dimethisoquin showed maximum stimulation at 100 microM, tetracaine and diphenhydramine at 300 microM, and QX-314 at 1 mM, while quinacrine, lidocaine and cocaine showed no or only slight stimulation. There was no correlation between local anesthetic activity, estimated by inhibition of the 22Na+ flux elicited by the sodium channel activator batrachotoxin, and the potency for stimulation of inositol incorporation. A quaternary, relatively weak, local anesthetic, QX-572, was the most potent agent in stimulation of inositol incorporation, while the next most potent agent was dibucaine, a tertiary, very potent, local anesthetic. Dibucaine did not affect the uptake of [3H]inositol by synaptoneurosomes. The incorporation of [3H]inositol into phosphoinositides was increased in calcium-free buffer. The presence of dibucaine resulted in further stimulation of [3H]inositol incorporation in calcium-free buffer. Although dibucaine and QX-572 markedly stimulated incorporation of [3H]inositol into phosphoinositides, only QX-572 significantly enhanced the incorporation of 32PO4(3-) into phosphoinositides. The results suggest that certain local anesthetics enhance a pathway involving an exchange reaction between inositol and the phosphoinositol ester bond of phosphatidylinositol, but do not markedly affect the de novo pathway of phosphoinositide synthesis.