Does general anesthetic-induced desensitization of the Torpedo acetylcholine receptor correlate with lipid disordering?

We have tested the hypothesis that general anesthetics stabilize the desensitized state of the nicotinic acetylcholine receptor by disordering its surrounding lipids. Acetylcholine receptor-rich postsynaptic membranes from the electroplaques of Torpedo were used in this study to obtain the highest possible receptor specific activity in native membranes. We examined 18 general anesthetics, including six inhalation agents, eight 1-alcohols, the enantiomers of 2-octanol, and two intravenous general anesthetics (pentobarbital and ethylcarbamate).

Stereoselectivity of channel inhibition by secondary alkanol enantiomers at nicotinic acetylcholine receptors.

Background: At the nicotinic acetylcholine receptor, long chain alkanols reduce, whereas short chain alkanols augment endplate currents. Using the enantiomers of five members of a homologous series of secondary alkanols (2-butanol through 2-octanol), we tested the hypothesis that these actions occur at a single hydrophobic site in the lumen of the channel. Small alkanols would bind to this site without blocking the channel, stabilizing the open state and enhancing the apparent affinity of the agonist for channel opening.

Continuous infusion of mivacurium in children.

Mivacurium is a new short-acting competitive neuromuscular blocking agent. Infusion requirements for the maintenance of a stable 90-99% muscle twitch depression were determined in 28 children anaesthetized with nitrous oxide and 1% halothane (inspired) in oxygen or nitrous oxide in oxygen and opioid. Neuromuscular block was assessed by monitoring the force of contraction of the adductor of the thumb during train-of-four (TOF) stimulation at 0.

Neuromuscular and cardiovascular effects of doxacurium in children anaesthetized with halothane.

The neuromuscular and cardiovascular effects of doxacurium chloride (BW A938U) were evaluated in 27 children (2-12 yr) anaesthetized with 1% halothane and nitrous oxide in oxygen. In nine children the incremental technique was used to establish a cumulative dose-response curve by train-of-four stimulation. The remaining children received either 30 or 50 micrograms kg-1 of the drug as a single bolus.

Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids.

While many theories of general anesthesia postulate a lipid site of action, there has been no adequate explanation for the lack of anesthetic potency of the highly hydrophobic primary alkanols with more than 12 carbons (the cut-off). Some work suggests that these nonanesthetic alcohols do not dissolve in membranes. Other work contradicts this and suggests that an anesthetic site on a protein provides a better explanation.

Neuromuscular and cardiovascular effects of mivacurium in children.

The neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) were evaluated in 90 children (2-12 yr) during N2O:O2 halothane or N2O:O2 narcotic anesthesia. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train-of-four stimulation at 0.1 Hz.

Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.

1. We have redetermined the anaesthetic potencies (EC50S) for a series of primary alkanols, to resolve uncertainties about the molecular dimensions of the anaesthetic site resulting from the use of data from different laboratories. 2.

Open versus closed chest cardiac massage in non-traumatic cardiac arrest.

Since the rediscovery and popularization of closed-chest cardiopulmonary resuscitation (CPR) in the early 1960s, this technique has largely replaced open-chest cardiac massage. However, in the ensuing quarter of a century, a large amount of data has been accumulated that seems to indicate that open-chest CPR is the physiologically superior method of cardiopulmonary resuscitation. This paper reviews that data comparing these two CPR modalities.

Anesthetic potencies of secondary alcohol enantiomers.

The Meyer-Overton rule has been interpreted to mean that general anesthetics act at a nonpolar site, either in a lipid bilayer or a protein. Optical isomers, also called enantiomers, are pairs of compounds with the same molecular formula and functional groups, but which differ in the arrangement of the groups around an "asymmetric" carbon atom and in the direction they rotate plane-polarized light. By definition, enantiomers that are anesthetics can distinguish between stereoselective and nonselective sites of anesthetic action.

Comparison of open-chest cardiac massage techniques in dogs.

Manual compression of the heart during open-chest cardiac massage (OCPR) has been shown to be superior to closed-chest compression. Our study sought to determine, in a canine model, the optimal hand position for manual compression of the heart. Twelve dogs were anesthetized with ketamine, an orotracheal tube was placed, and anesthesia was maintained with halothane and nitrous oxide.

Enflurane, halothane and isoflurane do not inhibit angiotensin converting enzyme activity.

We studied the effect of halothane, enflurane and isoflurane on angiotensin converting enzyme (ACE) activity using [3H]-benzoyl-phenylalanyl-alanyl-proline (BPAP) as a substrate. Isolated rabbit lungs were perfused in a recirculating system in vitro with BPAP in Krebs-Ringer solution. The rate of metabolism and per cent metabolism were determined before and after treatment for 30 minutes with four MAC multiples of enflurane, halothane or isoflurane.

Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells.

This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and internal Na and is inhibited competitively by external Na.