1Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 2Department of Anesthesiology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan*Corresponding author
Accepted for publication: January 18, 2002
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Abstract |
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Methods. Using in vivo brain microdialysis, we measured acetylcholine (ACh) release in the rat cerebral cortex in vivo during xenon anaesthesia.
Results. Xenon induced an initial increase in ACh release, followed by a gradual decrease. The level of Ach release at 40 min of xenon administration was significantly higher than the control.
Conclusions. Xenon activates CNS cholinergic cell activity followed by development of acute tolerance.
Br J Anaesth 2002; 88: 8668
Keywords: acetylcholine; anaesthetics, gases, xenon; brain, cerebral cortex
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Introduction |
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Based on the effects on the central nervous system (CNS) electrical activities, we have classified general anaesthetics into three categories: CNS depressant, CNS excitant, and epileptogenic,5 6 and reported that xenon7 and nitrous oxide7 are classified as excitatory. In contrast, isoflurane and sevoflurane are CNS depressant and epileptogenic,8 respectively.
We have reported that nitrous oxide enhances the release of acetylcholine (ACh), one of the major excitatory neurotransmitters in the rat cerebral cortex in vivo, whereas isoflurane and sevoflurane strongly suppressed ACh release.9 However, the effect of xenon has not been reported. In this study, we have examined the effects of xenon on ACh release in the rat cerebral cortex using an in vivo microdialysis technique.
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Methods and results |
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Perfusate samples obtained during the first 2 h after implantation of the probe were discarded to exclude the influence of isoflurane and probe insertion. The dialysates were then collected every 20 min in the sample loop of the automated sample injector, which was on line to an HPLC system. ACh was assayed using a HPLC-electrochemical detection system and a method described previously.9
After collecting three initial samples, 75% nitrogen was replaced with xenon (provided by Nippon Sanso Corp., Tokyo, Japan). After 5 min, the flow rate of xenon and oxgen was decreased to 300 and 100 ml min1, respectively, to reduce xenon consumption. Four hours later, xenon was stopped and the control gas mixture was replaced for 2 h. Xenon and carbon dioxide concentrations in the box were monitored continuously using a xenon gas monitor (Anzai Sogyo, Tokyo), and oxygen concentration was monitored by an anaesthetic gas monitor (Type 1304; Brüel & Kjær, Denmark).
Basal ACh release was determined as the mean of the three initial collections. All data are expressed as percentage of the basal value and are mean (SEM). Statistical significance was assessed by analysis of variance with repeated measures and, when significant F values were obtained, Fishers protected least significant difference test was used for significant differences between treatment means. A probability level of P<0.05 was considered significant.
The concentration of xenon in the box reached the predicted value within 5 min, and carbon dioxide was kept under 1% throughout the experiment. The rats were quiet during the control period. They became alert and moved around while they inhaled xenon for approximately 5 min, then became quiet and seemed to sleep lightly. Within 3 min after cessation of xenon administration, the rats became alert, and then after approximately 10 min, they became quite as seen during the control period.
Baseline ACh release was stable, and the content was 3.7 (0.5) pmol 20 min1. ACh release was significantly increased to reach the maximal level of 184.0 (28.5)% in the first fraction (020 min, P<0.01), followed by a gradual decline (Fig. 1). After 40 min of exposure to xenon, there were no differences from the control values except for a transient increase in the sixth fraction (100120 min).
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Comment |
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The gradual decline in ACh release during exposure to xenon observed in the present study suggests the development of acute tolerance to the CNS action of xenon, and is consistent with our previous report of xenon effects on R-MUA.7 Further studies are required to determine whether acute tolerance to other CNS actions of xenon develop in a similar fashion to nitrous oxide, such as the wakesleep cycle and EEG,5 and whether changes in ACh release are the cause or result of tolerance.
In conclusion, xenon produces a stimulant effect on cholinergic neurons projecting to the cerebral cortex. Furthermore, acute tolerance to this stimulant effect develops.
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References |
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