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Background In the perioperative period, plasma osmotic pressure, systemic blood pressure, and blood volume often change dramatically. Arginine vasopressin is a key factor in the regulation of these parameters. This study was performed to evaluate the direct and the mechanism of the actions of propofol on arginine vasopressin release from magnocellular neurosecretory neurons in the rat supraoptic nucleus. Methods Somatodendritic arginine vasopressin release from supraoptic nucleus slice preparations was measured by radioimmunoassay. Ionic currents were measured using the whole-cell mode of the patch-clamp technique in supraoptic nucleus slice preparations or in single dissociated supraoptic nucleus neurons of the rat. Results Propofol at concentrations greater than 10(-5) M inhibited the arginine vasopressin release stimulated by potassium chloride (50 mM). This inhibition by propofol was not reversed by picrotoxin, a gamma-aminobutyric acid(A)(GABA(A)) receptor antagonist, whereas arginine vasopressin release induced by glutamate (10(-3) M) was also inhibited by propofol at a clinically relevant concentration (10(-6) M). The latter effect was reversed by picrotoxin. Propofol evoked Cl- currents at concentrations ranging 10(-6) to 10(-4) M. Propofol (10(-6) M) enhanced the GABA (10(-6) M)-induced current synergistically. Moreover, propofol (10(-6) M) prolonged the time constant of spontaneous GABA-mediated inhibitory postsynaptic currents. Furthermore, propofol (10(-5) M and 10(-4) M) reversibly inhibited voltage-gated Ca2+ currents, whereas it did not affect currents induced by glutamate (10(-3) M). Conclusions Propofol inhibits somatodendritic arginine vasopressin release from the supraoptic nucleus, and the enhancement of GABAergic inhibitory synaptic inputs and the inhibition of voltage-gated Ca2+ entry are involved in the inhibition of arginine vasopressin release.

Background The cytokines play important roles in the pathophysiologic alterations associated with sepsis, but there are no reports about the effect of anesthetics on their production. Therefore, the authors examined the effect of ketamine on lipopolysaccharide (LPS)-induced and calcium ionophore A23187-induced tumor necrosis factor alpha (TNF-alpha) production in thioglycolate (TGC)-elicited peritoneal macrophages (MPs) in ddY mice. Methods Ketamine was added to TGC-elicited MPs at various times after the stimulation with LPS or A23187. After the MPs were stimulated by LPS or A23187 and incubated, TNF-alpha activities in the supernatant of MPs were determined by an L929 cytotoxic assay. In vivo, the ddY mice were injected intraperitoneally with TGC. Four days later, they were injected subcutaneously with ketamine and then injected intravenously with LPS. Two hours after the LPS challenge, TNF-alpha activities of the sera were determined. Results Ketamine suppressed both LPS-induced and A23187-induced TNF-alpha production in a dose-dependent manner. The simultaneous addition of ketamine to LPS-stimulated and A23187-stimulated MPs resulted in a 50% inhibition of TNF-alpha production at 20 micrograms/ml and 12.5 micrograms/ml, respectively. Ketamine also caused a significant suppression of TNF-alpha production even when added to the MPs 2 h after the LPS challenge. There was a significant decrease in A23187-induced TNF-alpha production in TGC-elicited MPs in a calcium-depleted medium when compared with that in a calcium-containing medium. Conversely, LPS-induced TNF-alpha production did not cause such a result. In addition, ketamine could suppress LPS-induced TNF-alpha production in TGC-pretreated mice in vivo. Conclusions Ketamine suppresses LPS-induced TNF-alpha production in both TGC-elicited MPs and TGC-pretreated mice.

A lighted stylet is a useful device for routine or difficult endotracheal intubation. 1-3 With light-guided intubation, the incidence of complications is reported to he low, but the larynx can be injured during the blind advancement of the endotracheal tube. 1 We report a case in which malpositioning of the epiglottis occurred after tracheal intubation with a lighted stylet, and difficulty was encountered in replacing the displaced epiglottis. This case prompted us to observe closely a series of intubations by use of a light wand.

Background Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET. Methods To assay [3H]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [3H]norepinephrine in the presence of intravenous anesthetics, including propofol, thiamylal, and diazepam. To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [3H]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [3H]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [3H]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. Results All of the intravenous anesthetics inhibited [3H]norepinephrine uptake in a concentration-dependent manner. The active concentrations of propofol (1-3 microm) and thiamylal (< or = 30 microm) were similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [3H]norepinephrine uptake. Propofol inhibited [3H]desipramine binding with a potency similar to that observed in [3H]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [3H]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 microm) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA. Conclusions These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.