Anesthesia, theory

The membrane enzyme luciferase, responsible for light emission in fireflies, is sensitive to anesthetics (20,21), and the concentrations of inhalational agents which inhibit luciferase are the same as those which cause general anesthesia. Studies of various classes of inhalational agents and luciferase demonstrated that above a certain chain length in a homologous series, a point is reached where higher members are not anesthetic. The same cut-off effect in efficacy is observed in anesthesia (22). This effect is not explainable by Hpid theory. 

Although an increase in membrane fluidity caused by anesthetic intercalation into the lipid bilayer was thought to result in general anesthesia, this theory was flawed in the following ways ... 

Among the earliest proposals to explain the mechanism of action of anesthetics is the concept that they interact physically rather than chemically with lipophilic membrane components to cause neuronal failure. However, this concept proposes that all anesthetics interact in a common way (the unitary theory of anesthesia), and it is being challenged by more recent work demonstrating that specific anesthetics exhibit selective and distinct interactions with neuronal processes and that those interactions are not easily explained by a common physical association with membrane components. Proposals for the production of anesthesia are described next. 

The induction of unconsciousness may be the result of exposure to excessive concentrations of toxic solvents such as carbon tetrachloride or vinyl chloride, as occasionally occurs in industrial situations (solvent narcosis). Also, volatile and nonvolatile anesthetic drugs such as halothane and thiopental, respectively, cause the same physiological effect. The mechanism(s) underlying anesthesia is not fully understood, although various theories have been proposed. Many of these have centered on the correlation between certain physicochemical properties and anesthetic potency. Thus, the oil/water partition coefficient, the ability to reduce surface tension, and the ability to induce the formation of clathrate compounds with water are all correlated with anesthetic potency. It seems that each of these characteristics are all connected to hydrophobicity, and so the site of action may be a hydrophobic region in a membrane or protein. Thus, again, physicochemical properties determine biological activity. 

Protein Theories. The direct interaction of inhalation anesthetics and proteins has been proposed as the cause of anesthesia. An inhalation agent, whether a noble gas or a fluorinated ether, could dissolve asymmetrically in a protein, Resultant conformational changes in the protein, if these changes occur, could then cause changes in biological activity. 

In theory, epidural and spinal blocks can be done at any level of the cord, but they are usually administered at the L3-4 or L4-5 vertebral interspace (i.e., caudal to the L-2 vertebral body, which is the point where the spinal cord ends). Epidural anesthesia is somewhat easier to perform than spinal blockade because the epidural space is larger and more accessible than the subarachnoid space. However, spinal anesthesia is... 

Works on the molecular basis of brain function and a theory of anesthesia. Continues his political activism, speaking widely about the dangers of radioactive fallout from bomb tests and the need for world peace... 

Another example is a theory of anesthesia by non-hydrogen bonding molecules such as cyclopropane, chloroform, and nitrous oxide, proposed by Pauling. These molecules are of a size and shape that can fit neatly into a hydrogen-bonded water structure with even larger open spaces than ordinary ice. Such structures, with molecules trapped in holes in a solid, are called clathrates. Pauling proposed that similar hydrogen-bonded microcrystals form even more readily in nerve tissue because of the presence of other solutes in the tissue. These microcrystals could then interfere with the transmission of nerve impulses. Similar structures of methane and water are believed to... 

General anesthetics are soluble in lipids. Only a few are soluble in water. Furthermore, there is a well known correlation between anesthetic potency and lipid solubility. It is the Meyer-Overton rule that has been known for 80 years to researchers in anesthesia.. This relationship was thoroughly studied and reexamined in recent years (See ). In its most modem form the lipid solubility or oil/water partition coefTicient is plotted against the so-called righting reflex taken for a measure of anesthetic potency. It is log 1/p where p is the effective anesthetic pressure in atmospheres required to suppress the righting reflex of mice in half of the experimental animals On this relationship arc based the unitary hypothesis and the hydrophobic site theory which state that all general anesthetics act by the same mechanism at the same molecular or sub-cellular sites of the membrane and that the sites are hydrophobic. 

These different cases will be examined more closely in the following sections. The underlying idea is that a unitary theory of anesthesia can be maintained only in as much as the forces that act involve in all cases only intennolecular interactions. But all the different types of intennolecular interactions have to be taken into consideration. 

A 68-year-old man was given 0.5% bupivacaine 4 ml or spinal anesthesia, and 5 minutes later complained of nausea and developed hypotension, loss of consciousness, and a tonic-clonic seizure. He had first-degree heart block 4 minutes after subarachnoid injection, followed 1 minute later by third-degree heart block, and then asystole. He was successfully resuscitated. Proposed theories included a reflex bradycardia resulting from reduced venous return and/or unopposed... 

Hide. B. Theories of anesthesia General perturbations veiMis spccitk receptors. In Fink. B. R. (cd.). Mechanisms of Anesthesia, vol 1 Pntgress in Anesthesiology. New York. Raven Press. 1980. pp. 1-5 StricharlA G. R. J. Dent. Res. 60.1460-1467. 1981. 

In a previous paper Bancroft and Rutzler reported on the experimental application of the Claude Bernard theory of anesthesia it was shown that sodium thiocyanate can relieve ether, amytal, and morphine anesthesia by peptizing the reversibly coagulated protein colloids of the central nervous system. Sodium thiocyanate was chosen because it peptizes proteins strongly and stands at the head of the lyotropic series of anions in this respect. The lyotropic series for egg albumin appears to be as follows CNS > I > Br > CIO3 > NO3 > Cl > CH3COO > SO4 > tar-... 

Claude Bernard s theory of anesthesia covers adequately the case of morphinism a reversible and invisibly minute coagulation takes place. 

---