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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.

The superoxide (O2.-) scavenging activity and neuroprotective effects of oxypurinol, a xanthine oxidase inhibitor, were compared with those of alpha-phenyl-N-tert-butyl nitrone (PBN). The rate constant for the reaction of oxypurinol with O2.- at pH 7.4 was 1.71 x 10(3) M(-1) s(-1) which was more than 100-fold that of PBN (1.65 x 10 M(-1) s(-1)). Oxypurinol inhibited the release of O2.- from stimulated neutrophils better than did PBN. However, oxypurinol did not attenuate the ischemic neuronal damage in gerbils, while PBN did. These results indicate that neither xanthine oxidase inhibiting activity nor O2.- scavenging activity correlates to the therapeutic efficacy of neuroprotective agents in ischemic-reperfusion injury.

We have compared the effects of xenon and nitrous oxide on central nervous system (CNS) electrical activity during sevoflurane anaesthesia in cats by recording the electroencephalogram (EEG), multi-unit activity of the midbrain reticular formation (R-MUA) and somatosensory evoked potentials (SEP). Basal anaesthesia with 2% and 5% sevoflurane was used. With 2% sevoflurane, 70% xenon initially produced rhythmic slow waves which were followed by bursts of high-amplitude sharp waves interrupted by low amplitude slow waves on the EEG. Xenon induced an initial increase, followed by a decrease in R-MUA. Nitrous oxide 70% decreased the amplitude of the EEG activity which was associated with an increase in R-MUA. Xenon suppressed the amplitude of both the initial positive and negative deflections of the SEP to a greater extent than nitrous oxide. With 5% sevoflurane anaesthesia, both anaesthetics increased the frequency of spikes on the EEG and facilitated R-MUA. These findings indicate that xenon has a stimulatory action on CNS background activity and a suppressive action on CNS reactive capability which is more potent than that of nitrous oxide.

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.

We compared the effects of xenon (Xe) on the spinal cord dorsal horn neurons with those of nitrous oxide (N 2 O) in cats anesthetized with chrolarose and urethane. We assessed the potency of both anesthetics by the inhibition of wide dynamic range neuron responses evoked by cutaneous noxious (pinch) stimulation to a hindpaw. During 70% Xe inhalation, the responses of 7 of 11 neurons to pinch stimulation were suppressed. N 2 O, 70%, suppressed it in 8 of 11 neurons. The potency of Xe and N 2 O was compared in six neurons that were suppressed by both anesthetics. After 20 min of Xe inhalation, the response to pinch was suppressed to 49.5% ± 8.2% (mean ± SE), while N 2 O, 70% in oxygen, suppressed it to 45.9% ± 7.9%. The difference between N 2 O and Xe was not significant. We conclude that Xe and N 2 O suppress the spinal cord dorsal horn neurons to a similar degree.

Patients undergoing microvascular decompression surgery often experience postoperative nausea and vomiting (PONV). However, there is little information about the incidence of PONV after microvascular decompression. We hypothesized that microvascular decompression is an especially high-risk procedure for PONV in patients undergoing neurosurgery, and investigated risk factors related to PONV after neurosurgery. All patients who underwent craniotomy in our institution during a period of 2 years were investigated retrospectively. Medical charts were reviewed to identify PONV during the 24-h postoperative period and related risk factors. Multivariate logistic regression analysis was conducted to elucidate the impact of microvascular decompression on PONV after craniotomy. Among 556 craniotomy cases, 350 patients met the inclusion criteria. Multivariate logistic regression analysis showed that microvascular decompression was an independent risk factor for PONV after craniotomy (odds ratio 5.38, 3.02–9.60), in addition to female gender, non-smoker status, amount of intraoperative fentanyl administered, and cerebrovascular surgery. In this retrospective study, microvascular decompression surgery was an especially high-risk factor for PONV in patients undergoing craniotomy. It may be necessary to adopt a combination of prophylactic methods to reduce the incidence of PONV after microvascular decompression.

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.

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.

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.

To provide a neurochemical basis for the central nervous system actions of nitrous oxide, the changes of brain dopamine (DA), serotonin (5-HT), norepinephrine (NE), and metabolites of DA and 5-HT were studied in rats. Thirty male Wistar rats were assigned to one of five groups according to the type of gas and the duration of gas exposure. The rats in one group, which served as control, were exposed to air for 30 min, and the rats in four other groups were exposed to 75% nitrous oxide in oxygen for 0.5, 1, 2, and 4 h, respectively. Animals were killed with microwave irradiation, and the brains were divided into seven sections: the cerebral cortex, cerebellum, striatum, hippocampus, midbrain-thalamus, hypothalamus, and medulla-pons. The contents of NE, DA, 3,4-dihydroxyphenyl-alanine (DOPAC), homovanillic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in each discrete area were measured with high-performance liquid chromatography. Nitrous oxide had no significant effect on the contents of NE, 5-HT, nor 5-HIAA, but decreased that of DA in the striatum and midbrain-thalamus after 4 h of exposure (P < 0.05). Levels of DOPAC, but not DA, in the cerebral cortex and medulla-pons were increased significantly at exposures up to 2 h (P < 0.05), but were not significant from control levels after a 4-h exposure. Increased levels of DOPAC indicate that nitrous oxide increases dopaminergic neuronal activities in the mesocortical projection and the medullary network.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxia-inducible factor 1 (HIF-1) is the main transcription factor responsible for hypoxia-induced gene expression. Perioperative drugs including anesthetics have been reported to affect HIF-1 activity. However, the effect of fentanyl on HIF-1 activity is not well documented. In this study, we investigated the effect of fentanyl and other opioids on HIF-1 activity in human SH-SY5Y neuroblastoma cells, hepatoma Hep3B cells, lung adenocarcinoma A549 cells and mice. Cells were exposed to fentanyl, and HIF-1 protein expression was examined by Western blot analysis using anti-HIF-1α and β antibodies. HIF-1-dependent gene expression was investigated by semi-quantitative real-time reverse transcriptase (RT)-PCR (qRT-PCR) and luciferase assay. Furthermore, fentanyl was administered intraperitoneally and HIF-1-dependent gene expression was investigated by qRT-PCR in the brains and kidneys of mice. A 10-μM concentration of fentanyl and other opioids, including 1 μM morphine and 4 μM remifentanil, induced HIF-1α protein expression and HIF-1 target gene expression in an opioid receptor-dependent manner in SH-SY5Y cells with activity peaking at 24h. Fentanyl did not augment HIF-1α expression during hypoxia-induced induction. HIF-1α stabilization assays and experiments with cycloheximide revealed that fentanyl increased translation from HIF-1α mRNA but did not stabilize the HIF-1α protein. Furthermore, fentanyl induced HIF-1 target gene expression in the brains of mice but not in their kidneys in a naloxone-sensitive manner. In this report, we describe for the first time that fentanyl, both in vitro and in vivo, induces HIF-1 activation under non-hypoxic conditions, leading to increases in expression of genes associated with adaptation to hypoxia.

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28–32°C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1α protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O2 conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O2 atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1α neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

The effects of i.v. administration of a nitric oxide (NO) synthase inhibitor, l -N G - nitroarginine ( l -NOArg), on the increase in cerebral cortical blood flow (cortical BF), following either electrical stimulation of the nucleus basalis of Meynert (NBM), whose cholinergic fibers project to the cortex, or hypereapnia with 10% CO2 inhalation, were studied in anesthetized rats. Cortical BF was measured using laser Doppler flowmetry. The threshold intensity of electrical stimulation of the NBM (0.5 ms, 50 Hz for 10 s) that induced an increase in regional cortical BF was defined as 1T. The cortical BF was increased on a stimulus intensity dependent manner at 1T 5T intensities tested, l -NOArg was administered cumulatively i.v. starting from 0.3 mg/kg, then 3 mg/kg, and 30 mg/kg. Time interval between each cumulative administration of l -NOArg was approximately 40 min. Three and 30 mg/kg of l -NOArg significantly reduced the NBM stimulation-induced increase of cortical BF at intensities of 2T and 3T. The response at an intensity of 5T was reduced only by 30 mg/kg of l -NOArg to about half the control response. The reduced responses at 2T, 3T, and 5T were reversed following the i.v. administration of a physiological precursor of NO, l -Arg (300 mg/kg). Inhalation of 10% CO2 for 15 s induced an increase in cortical BF which was not influenced by l -NOArg and l -Arg. These results suggest that NO is a necessary factor in the vasodilatation of the cortical BF that is brought about by cholinergic fibers originating in the NBM.

It is predictable that since distal gastrectomy (DG) with Billroth I anastomosis involves no procedures caudal to transverse colon, the effects of the surgical wound are the main cause of adhesive obstruction. Thus, it is an appropriate operation to test the efficiency of a synthetic absorbable adhesion barrier (Seprafilm).The subjects were 282 patients diagnosed with gastric cancer who underwent open DG with Billroth I anastomosis between 2001 and August, 2005. Seprafilm was not used in any patients operated on before April, 2003 (n = 169), but it was used in all patients operated on from May 2003 onward (n = 113). We retrospectively compared the incidences of adhesive obstruction in the Seprafilm group and the non-Seprafilm group.The cumulative incidence of adhesive obstruction was significantly lower in the Seprafilm group than in the non-Seprafilm group (P = 0.021). The respective incidences of adhesive obstruction 2 years after surgery were 0.9% and 6.5%. Multivariate analysis of the occurrence of adhesive obstruction revealed no significant differences in sex, age, body mass index, operation time, blood loss, or degree of lymph-node dissection; however, it revealed a significant difference in relation to the use of Seprafilm (P = 0.049).In this series, Seprafilm reduced the incidence of adhesive obstruction after DG significantly; however, a prospective randomized study will be necessary to confirm this result.

The effect of a focal stimulation of the magnocellular nucleus of the basal forebrain at two different areas, the nucleus basalis of Meynert (NBM) and the substantia innominata (SI), on local cerebral blood flow (CBF) in the frontal, parietal and occipital cortices was examined in urethane-anesthetized rats. The stimulation, either electrically or chemically, of both the NBM and SI produced significant CBF increase in all these 3 cortices ipsilateral to the stimulation site. This fact suggests that activation of neurons originating in the NBM and SI produces widespread increases in local CBF in the ipsilateral cerebral cortex.

Mannitol is used commonly as an osmotic diuretic to reduce intracranial pressure during the perioperative period of craniotomy. The rapid administration of mannitol solution can cause an imbalance of electrolytes such as sodium and potassium. Here, we report two cases of mannitol-induced hyperkalemia. We demonstrate that administration of mannitol during craniotomy increases potassium iron concentration, and in some cases it may cause disturbance of cardiac function.

Liver transplantation for patients with severe portopulmonary hypertension (PPHTN) has been associated with high mortality. We conducted perioperative management of two patients with severe PPHTN for living-donor liver transplantation. The first case was a 17-year-old male with biliary atresia. He developed dyspnea at the age of 14, for which he was treated with intravenous epoprostenol for 8 months. As a result, the mean pulmonary artery pressure (MPAP) was reduced from 61 to 40 mmHg. Intraoperatively, he was treated with intravenous epoprostenol and nitric oxide (NO) inhalation. His intraoperative course was uneventful but he died from right heart failure on postoperative day (POD) 11. The second case was a 6-year-old girl with biliary atresia. When she was 5 years old, examination for a persistent cough revealed MPAP of 49 mmHg. Neither intravenous epoprostenol nor NO inhalation was effective, and she twice showed transient pulmonary hypertension during the operation. She was extubated 14 hours after the surgery, transferred out of ICU on POD 3 and discharged from the hospital on POD 99. When we compare the two cases, the factors responsible for the success of the management of the second case appear to be early extubation and the short duration of PPHTN.

IMPLICATIONS This report concerns a case for which the intraoperative use of magnesium sulfate as an adjunct to the conventional use of nicardipine was effective for managing a pediatric patient with pheochromocytoma who was undergoing a laparoscopic operation.

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. Br J Anaesth 2002; 88: 866–8

Glutamate is a major neural transmitter of noxious stimulation in the spinal cord. We measured glutamate release from rat spinal synaptoneurosomes by using an enzyme-linked fluorimetric assay. Glutamate was released from spinal cord synaptoneurosomes in response to the addition of 30 mM potassium chloride, 1 mM 4-aminopyridine, or 1 mM ionomycin in the presence of external calcium. There was less release of glutamate in the absence, versus the presence, of external calcium. Clonidine significantly reduced the level of glutamate released from the spinal cord synaptoneurosomes. Tetradecanoyl phorbol acetate, an activator of protein kinase C, enhanced glutamate release. Forskolin, a protein kinase A activator, had no effect on the glutamate efflux. Our data indicate that glutamate released in the spinal cord is dependent on protein kinase C but is independent of the protein kinase A pathway. They also suggest that the inhibition of glutamate release may be the underlying mechanism of antinociception by clonidine at the spinal cord level. Implications: We demonstrated that synaptoneurosomes from rat spinal cord could release glutamate in response to depolarization. We showed that an activator of protein kinase C increased glutamate released from spinal cord synaptoneurosomes but that clonidine decreased it. Glutamate release may be one of the mechanisms of antinociception at the spinal cord level. (Anesth Analg 1999;88:1401‐5)

Background Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. Methods Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. Results Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. Conclusion The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.

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.

UNLABELLED The efficacy of epinephrine in prolonging spinal analgesia has recently been confirmed in the lumbosacral but not in the thoracic, segments. Most previous studies used doses of epinephrine smaller than 0.3 mg. We studied the effects of 0.2, 0.4, or 0.6 mg of epinephrine added to hyperbaric lidocaine 60 mg in 7.5% dextrose solution for spinal anesthesia. Eighty patients were randomly divided into four groups: Group A received lidocaine without epinephrine, Group B received lidocaine plus 0.2 mL (0.2 mg) of epinephrine 1:1000 solution, Group C received lidocaine plus 0.4 mL (0.4 mg) of epinephrine, and Group D received lidocaine plus 0.6 mL (0.6 mg) of epinephrine. The maximal cephalad sensory level was between T2 and T3 for all groups. The median times for analgesia to regress two and four segments were significantly prolonged in Group D, but not in either Group B or C, compared with those in Group A. Times for regression to T12 and L3 were significantly prolonged in Groups B, C, and D compared with Group A. We conclude that the dose-dependent relationship of spinal analgesia can be applied to epinephrine, and that larger doses prolong lidocaine spinal anesthesia in the thoracic as well as the lumbosacral dermatomes. IMPLICATIONS Prolongation of lidocaine spinal analgesia by intrathecal epinephrine is established in the lumbosacral, but not in the thoracic, dermatomes. Three doses of epinephrine--0.2, 0.4, and 0.6 mg--were compared. A dose-dependent response and significant prolongation with the 0.6-mg dose in the thoracic dermatomes were confirmed.

The superoxide (O 2 ⋅− ) scavenging activity and the neuroprotective effects of pterin-6-aldehyde (P6A), a xanthine oxidase inhibitor, were examined and compared with those of α -phenyl- N - tert -butyl nitrone (PBN), a spin trapping agent. The scavenging activity of P6A was more potent than that of PBN by 150-fold in neutrophil/phorbol myristate acetate O 2 ⋅− generating system. P6A attenuated the neuronal damage with a much smaller dose and a greater efficiency than PBN in global brain ischemia in gerbils. These findings suggest that P6A is a more potent neuroprotective agent than PBN and has possible therapeutic effects against various diseases in which O 2 ⋅− is involved.

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.

The effects of morphine on the reflex discharges in sympathetic efferents recorded from branches of the inferior cardiac nerve (ICN) were studied in rats anesthetized with α-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited by single shock electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers of the tibial nerve, respectively. Application of morphine either into the femoral vein or into the subarachnoid space of the cisterna magna enhanced both the A- and C-reflexes in a dose-dependent manner, while application of morphine into the intrathecal space of the lumbar spinal cord selectively inhibited C-reflexes. All effects of morphine were antagonized by naloxone. Application of morphine via the internal carotid artery to central nervous structures above the brainstem had no effect on the somatocardiac sympathetic reflexes. It is concluded that in the anesthetized rat morphine in a dose-dependent and naloxone-reversible manner (1) depresses spinal transmission of C-afferent activity, whereas (2) at the brainstem it enhances the transmission of somatocardiac sympathetic A- and C-reflexes.

The effect of noxious or innocuous mechanical stimulation of cutaneous areas (face, forelimb and paw, back, hindlimb and paw) on cerebral blood flow in cortex was examined with laser Doppler flowmetry in anesthetized rats. Pinching of the face, forepaw and hindpaw for 15 s produced significant increases of systemic blood pressure and of cortical blood flow, whereas pinching of the back or brushing of any cutaneous area produced no significant changes in either parameter. Following spinal transection at the first thoracic level, the blood pressure response to forepaw pinching was suppressed, whereas the increase in cortical blood flow still took place. Thus the results suggest that the increase in cortical blood flow following cutaneous noxious stimulation is, in part at least, independent of changes in blood pressure and of any concomitant vasodilatation.

Nitric oxide (NO) synthase inhibitor (N”-nitro-Larginine methyl ester [L-NAME]) has been reported to reduce minimum alveolar anesthetic concentration (MAC) of halothane when administered intravenously (IV) 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 IV, 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 IV (10-30 mg/kg) administration of L-NAME. ICV (100 pg) and IT (100 pg 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. (Anesth Analg 1994;78:1154-7)

We analyzed the effect of a new volatile anesthetic, sevoflurane (2%-5% in oxygen) on the electroencephalogram (EEG) of the neocortex, amygdala, and hippocampus, cortical somatosensory evoked potential (SEP), and brainstem reticular multiunit activity (R-MUA) in cats. Sevoflurane suppressed the background activity of the neocortex more than the amygdala and hippocampus. With increasing concentration of sevoflurane, the cortical EEG progressed from high-amplitude slow waves to a suppression-burst pattern, which was followed by an isoelectric pattern and then spikes with isoelectricity. The amplitude of the SEP was augmented and the R-MUA was suppressed by sevoflurane in a dose-related manner. Repetitive peripheral electrical stimulation induced generalized seizures at 5% sevoflurane in 2 of 13 cats. These results suggest that sevoflurane suppresses the background central nervous system electrical activities in a dose-related manner, leaving the reactive capabilities facilitated at deep anesthesia.