Nitrous oxide depresses somatocardiac sympathetic A- and C-reflexes in anesthetized rats.

Effect of nitrous oxide (N2O) on the somatosympathetic A- and C-reflexes was investigated using artificially ventilated rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited in the inferior cardiac nerve by electrical stimulation of A and C afferent fibers of the tibial nerve, respectively. Both reflexes were depressed by inhalation of N2O for 20 min. The depression was greater in the C-reflex than in the A-reflex. The depressive effects of N2O on both reflexes were unchanged after pretreatment with intravenous naloxone (0.2 or 2.0 mg/kg) or by prolongation of the inhalation of N2O for 2 h. These results suggest that the opioid receptor is not involved and that acute tolerance is not developed in the depressive action of N2O on the somatosympathetic A- and C-reflexes.

[Perioperative management of congenital antithrombin III deficiency].

We describe perioperative management of a patient with congenital antithrombin III (ATIII) deficiency, who had an oral surgical operation under general anesthesia. The patient had a history of thrombosis. Preoperative plasma ATIII activity was 52% of the normal value. ATIII concentrates had been administered to prevent perioperative thrombosis. During the operation, the plasma ATIII level was maintained at 128%, and there was no episode of abnormal hemostasis. But, he complained of pain in his left leg probably due to thrombosis on the third day after operation, when his plasma ATIII activity was supposed to be approximately 70%. It is recommended that the plasma ATIII level is maintained, at least, above 80% for one week after the operation.

Nociceptin system does not affect MAC of volatile anaesthetics.

BACKGROUND: Nociceptin is the endogenous agonist of the opioid receptor-like (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the brain and spinal cord, which are target organs of general anaesthetics. As nociceptin has been reported to be involved in modulating pain mechanisms and stress responses, it is possible that the activity of the nociceptin system affects the anaesthetic potency of general anaesthetics. To address this possibility, we investigated the minimum alveolar concentrations (MACs) of various volatile anaesthetics in nociceptin receptor knockout mice (NOP-/-) and wild-type mice (NOP+/+). METHODS: We used male NOP-/- mice and NOP+/+ mice. MACs for halothane, isoflurane and sevoflurane were determined by the tail-clamp method. RESULTS: MACs for halothane, isoflurane and sevoflurane in NOP-/- mice were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice, MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07) and 3.38 (0.09)%, respectively. CONCLUSION: MACs in NOP-/- mice did not significantly differ from those in NOP+/+ mice for halothane, isoflurane and sevoflurane. This result suggests that the nociceptin system does not affect the anaesthetic potency of volatile anaesthetics.

The cerebral cortex origin of enflurane-induced generalized seizure in cats.

The role of sensorimotor cortex (anterior and posterior sigmoid gyri) as the origin of enflurane-induced generalized seizures was examined and compared to that of lidocaine-induced seizures in cats. The inhaled enflurane concentration was adjusted at 3.5% in oxygen, the maximum potency to induce generalized seizures. Repetitive electrical stimulation with supramaximum intensity at a forepaw (2 Hz, 0.5 ms, 10 V) induced generalized seizures, which ended with a sudden appearance of isoelectricity in the electroencephalogram (EEG), the so-called "postictal depression." Repetitive auditory stimuli also induced similar grand mal-type EEGs. Unilateral ablation of the sensorimotor cortex completely blocked the induction of generalized seizures by contralateral somatosensory stimuli. However, it had little effect on the induction of seizures by ipsilateral somatosensory stimuli or bilateral auditory stimuli. In contrast, bilateral ablation of the sensorimotor cortex did not have a significant effect on the lidocaine-induced seizures. These findings indicate that the involvement of the sensorimotor cortex is essential for the development of enflurane-induced but not lidocaine-induced seizures.

Xenon has greater inhibitory effects on spinal dorsal horn neurons than nitrous oxide in spinal cord transected cats.

UNLABELLED: Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons. IMPLICATIONS: Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.

Effects of inhalation anaesthetics on the release of acetylcholine in the rat cerebral cortex in vivo.

By analysing the EEG, reticular multi-unit activity and behavioural changes, we have classified general anaesthetics into three groups: central nervous system (CNS) depressant, CNS excitant and epileptogenic agents. Changes in CNS neural activity are associated with alteration in transmitter release. We have attempted to clarify the actions of widely used inhalation anaesthetics, such as isoflurane (CNS depressant), nitrous oxide (CNS excitant) and sevoflurane (epileptogenic) on acetylcholine (ACh) release in the cerebral cortex using brain microdialysis. ACh release was suppressed by isoflurane and sevoflurane in a dose-related manner but recovered on wash-out. There were no significant differences between the effects of sevoflurane and isoflurane at the same MAC values. In contrast, ACh release was enhanced significantly by nitrous oxide. These findings indicate that the response of the cortical cholinergic cells to different anaesthetics reflects their neurophysiological characteristics, that is whether they stimulate or suppress CNS neurones.

Sevoflurane, enflurane and isoflurane have no persistent postanaesthetic effects on the central nervous system in cats.

Several reports have appeared on postanaesthetic convulsive disorders in humans after enflurane and isoflurane anaesthesia. However, it is controversial if enflurane induces epileptiform electroencephalogram (EEG), abnormal behaviour, or both, lasting for several days after anaesthesia in laboratory animals. We chronically implanted electrodes for EEG recording in the cortex, medial amygdala and dorsal hippocampus, and for reticular multi-unit activity (R-MUA) in the midbrain reticular formation in five cats. Two weeks later they were anaesthetized with 5.0% sevoflurane, 3.5% enflurane or 4.8% isoflurane for 3-4 h. EEG recordings, R-MUA and behaviour were observed for 1-3 h, during both wakefulness and sleep, every day for 5-7 days after anaesthesia. None of the cats showed abnormal behaviour, or EEG or R-MUA abnormalities after any of the anaesthetics, not only during wakefulness but during slow-wave and paradoxical phases of sleep. These results suggest that if seizures occur after anaesthesia, volatile anaesthesia itself may not be the cause.

Dexmedetomidine reduces seizure threshold during enflurane anaesthesia in cats.

Dexmedetomidine is an alpha 2 agonist and has been reported to have proconvulsant actions. To investigate the interaction of dexmedetomidine with convulsant anaesthetics, we studied effects on seizure threshold in cats during enflurane anaesthesia. Cats were prepared with chronic implantation of electrodes for recording of the cortical electroencephalogram (EEG) and midbrain reticular formation multi-unit activity (R-MUA). Seizure threshold, the reciprocal of the number of electrical stimuli required to induce generalized EEG seizure activity x 1000 (seizure induction index (SII)), was assessed. The effects of dexmedetomidine 1, 10 and 100 micrograms kg-1 i.v. and yohimbine 500 micrograms kg-1, an alpha 2 antagonist, on SII during 3.5% enflurane anaesthesia were investigated. Dexmedetomidine significantly increased SII at 10 and 100 micrograms kg-1, and this effect was reversed by yohimbine. We found that high-dose dexmedetomidine reduced seizure threshold during enflurane anaesthesia.

Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo.

BACKGROUND: We have reported previously the effects of several anaesthetics on cholinergic activity in the central nervous system (CNS). In this study, we report the effects of xenon on cholinergic cell activity. 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.

Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum.

BACKGROUND: Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS: Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS: In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION: The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

Chronic treatment with nitric oxide synthase (NOS) inhibitor profoundly reduces cerebellar NOS activity and cyclic guanosine monophosphate but does not modify minimum alveolar anesthetic concentration.

We previously found that acute administration of a nitric oxide synthase (NOS) inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a recent study has suggested that brain NOS activity could not be inhibited by more than approximately 50% by acute administration of L-NAME. To investigate the effect of marked inhibition of NOS activity on the MAC of halothane, we measured cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels, and halothane MAC in rats chronically treated with L-NAME and compared the results to those of the saline-treated control group. Although the cerebellar NOS activity and cGMP levels were significantly decreased (14% and 2.7% of control, respectively) by L-NAME, the value of the halothane MAC was not significantly affected. These results suggest that the anesthetic action of halothane, as measured by its MAC in rats, is not related to NOS activity or cGMP levels in the brain.

Nitric oxide synthase inhibitor does not reduce minimum alveolar anesthetic concentration of halothane in rats.

Nitric oxide (NO) synthase inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) has been reported to reduce minimum alveolar anesthetic concentration (MAC) of halothane when administered intravenously (i.v.) and to reduce thermal hyperalgesia, or produce antinociception in the formalin test, when administered intracerebroventricularly (ICV) or intrathecally (IT). This study attempts to identify the site(s) in the central nervous system (CNS) where L-NAME acts to reduce the halothane MAC. For this purpose, we examined the effects of i.v., ICV, and IT administration of L-NAME on the halothane MAC in rats. In contrast to an earlier study, we did not observe any decrease in the halothane MAC after i.v. (10-30 mg/kg) administration of L-NAME. ICV (100 micrograms) and IT (100 micrograms and 1 mg) administration of L-NAME also did not alter the halothane MAC. These findings indicate that the L-arginine-NO pathway is not involved in the mechanism of action of halothane to suppress mechanical nociceptive response or in the nociceptive neural mechanism of mechanical stimulation.

Simultaneous measurement of intestinal blood flow and plasma levels of vasoactive substances in a case of early dumping syndrome. Case report.

Increase in intestinal blood flow was observed in a patient with postprandial hypotension. Simultaneous measurement of hemodynamic parameters and plasma levels of gut hormones revealed that the release of various vasoactive substances and resulting vasodilation of abdominal organs were responsible for the vasomotor changes of early dumping syndrome.

Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex.

BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has psychotomimetic side effects. Recent studies have shown that noncompetitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactions has not been established. METHODS: The effects of diazepam and halothane on c-Fos expression induced by ketamine were studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1.0 and 1.8%), was administered continuously from 10 min before ketamine administration until brain fixation. Two hours after ketamine injection, rats were perfused and their brains fixed and extracted. Brain sections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. RESULTS: Ketamine induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dose-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent manner, leaving the thalamus relatively unaffected. CONCLUSION: Halothane and diazepam inhibited ketamine-induced c-Fos expression in the cingulate and retrosplenial cortices, leaving the thalamus relatively unaffected.

Perioperative plasma concentrations of endothelin and natriuretic peptides in children undergoing living-related liver transplantation.

To investigate the clinical significance of endothelin (ET), natriuretic peptides, and the renin-angiotensin-aldosterone system in pediatric liver transplantation, we measured plasma levels of ET, atrial and brain natriuretic peptides (ANP, BNP), aldosterone, and plasma renin activity in 18 patients (aged 0.5-12 yr; median 1 yr) undergoing living-related liver transplantation due to congenital biliary atresia and severe liver cirrhosis. Before transplantation, the plasma ET level (28.9 +/- 2.5 [mean +/- SEM] pg/mL) was increased compared with that of healthy children (10-18 pg/mL), but decreased during the anhepatic phase (22.5 +/- 1.6 pg/mL). It increased again after reperfusion and remained at high levels in the early postoperative period (postoperative day 3, 27.8 +/- 3.0 pg/mL). Plasma levels of ANP and BNP and aldosterone and plasma renin activity were also high before surgery. Plasma ANP and BNP did not change significantly during surgery. After transplantation, plasma BNP significantly increased, and plasma ANP tended to increase. Plasma aldosterone increased markedly during the anhepatic phase, although plasma renin activity decreased. After transplantation, plasma aldosterone and plasma renin activity both decreased to within normal levels. Mean arterial blood pressure increased gradually after reperfusion and surgery (postoperative day 3, 35.7 +/- 5.2% increase). No substantial differences in these variables occurred between the younger (< or = 1.0 yr, n = 9) and older patients (> 1.0 yr, n = 9). These results suggest that ET production in the cirrhotic liver is augmented and ET, natriuretic peptides, and the renin-angiotensin-aldosterone system all play some role in the circulatory regulation during perioperative periods of pediatric liver transplantation.