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To examine the effect of halothane on the cytosolic Ca2+ concentration ([Ca2+]i)-tension relationship of rat aortic smooth muscle.Rat aortic rings without endothelia were loaded with the fluorescent Ca2+ indicator, Fura PE3-AM, and then mounted in organ baths. The changes in isometric tension and [Ca2+]i were measured simultaneously. In one series ionomycin (10 nM-3 microM) was added to normal Krebs' solution cumulatively in the absence and presence of halothane (1.5%, 3%). In the other series, CaCl2 (0.3-3 mM) was added to Ca2+-free Krebs' solution including high KCl (50 mM), phenylephrine (100 nM) or prostaglandin F2alpha (PGF2alpha, 1-3 microM) in the absence and presence of halothane (1.5%, 3%). The linear part of [Ca2+]i-tension relationship was analyzed by a linear regression.Halothane, 1.5%, had no effect on the normal [Ca2+]i-tension relationship obtained with the calcium ionophore, ionomycin (10 nM-3 microM), but halothane 3% decreased the slope of the relationship (0.239 +/- 0.037 for control and 0.110 +/- 0.010 for halothane 3%, P0.05). Halothane, 1.5% and 3%, did not change the [Ca2+]i-tension relationship obtained with CaCl2 (0.3-3 mM) in the presence of high KCl (50 mM) or phenylephrine (100 nM). In contrast, halothane, 3%, inhibited the intercept of [Ca2+]i-tension relationship obtained with CaCl2 (0.3-3 mM) in the presence of prostaglandin F2alpha (PGF2alpha, 1-3 microM) (45.708 +/- 4.233 for control and 26.997 +/- 2.522 for halothane 3%, P0.01).Halothane decreases the Ca2+ sensitivity and that in the presence of PGF2.

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.

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system is involved in glutamatergic neurotransmission. The current study determined the effects of propofol, ketamine and midazolam on rat cerebellar cGMP formation, attempting to clarify whether the effect was due to suppression of NO-cGMP system or to direct interaction with glutamatergic receptors.Cerebellar slices, obtained from six- to eight-day-old Wistar rats, were pretreated with propofol (10 microM-1 mM), ketamine (10-100 microM) or midazolam (1-100 microM) for 30 min. and then stimulated with L-glutamate (3 mM), N-methyl-D-aspartate (NMDA, 0.1 mM), kainate (0.1 mM) or sodium nitroprusside (SNP, 0.3 mM) (n = 5-11 for each group). The levels of cGMP were determined by radioimmunoassay.None of the anaesthetics studied altered cGMP levels when no stimulant was given. Propofol (10 microM-1 mM) suppressed L-glutamate-, NMDA-, kainate- and SNP stimulated cGMP formation in a concentration-dependent manner, the sensitivity to propofol was in the order of NMDAkainateL-glutamate. SNP. Ketamine (10-100 microM) suppressed L-glutamate- and NMDA-stimulated cGMP formation, but did not suppress kainate- or SNP-stimulated cGMP formation. Midazolam (10-100 microM) did not affect NMDA-, L-glutamate- or SNP-stimulated cGMP formation, but suppressed kainate-induced formation.The inhibitory effects of propofol, ketamine and midazolam on cGMP formation in rat cerebellar slices are due mainly to interaction with receptors for excitatory amines, and not due to the suppression of nitric oxide synthase or guanylate cyclase activities.

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.

Halothane suppresses platelet aggregation in vitro and ex vivo, and prolongs bleeding time. In a previous in vitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregation ex vivo.Thirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentone i.v., and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5-10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1-1.5 times the minimum alveolar concentration (MAC) and mean arterial pressures were between 80-120% of preanaesthetic values.In all samples obtained during sevoflurane anaesthesia (n = 15), ADP and epinephrine could not induce secondary aggregation, although they did induce primary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained during anaesthesia.Sevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.

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.

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.

Patients who underwent subtotal esophagectomy were extubated on the first postoperative day in order to avoid postoperative pulmonary complications and discomfort. Extubation was carried out if the patient satisfied the following criteria: no ischemic change in the mucosa, PaO2 greater than 100mmHg, and PaCO2 less than 45mmHg under 2cm H2 O CPAP or a T-piece with an FiO2 of 40%. Fiberoptic bronchoscopy (FBS) was then performed under topical anesthesia to aspirate sputum in the bronchial trees. We retrospectively studied the duration of tracheal intubation and the number of days, on which FBS was required after extubation in 41 patients. They were analyzed with regard to two preoperative measures; one-second forced expiratory volume (FEV 1) greater or less than 2.0L, and smoking history. The duration of tracheal intubation except for two tracheostomy cases was 1.8±1.7 days (mean±SD). Twenty-seven patients (66% of all patients) were extubated on the first postoperative day. The duration of intubation was not affected significantly by the risk factors. However, four patients in whom the duration of intubation was longer than 3 days, and two who required tracheostomy for long-term pulmonary care, were all smokers. FBS was required for 3.7±2.0 days after surgery. The duration of FBS was not affected by the value of FEV 1. However, smokers required FBS for a longer period (4.1±2.2 days) than non-smokers (2.9±1.2 days, p

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ET-LI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET-LI levels in plasma and CSF (n = 24) were 12.4 +/- 2.0 (mean +/- s.d.) and 9.1 +/- 1.2 pg.ml-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8 +/- 7.8 pg.ml-1, n = 8) were higher than the normal values (P < 0.05), and became further elevated after surgery (22.5 +/- 9.4 pg.ml-1). ET-LI levels in plasma and CSF one day after surgery were 18.7 +/- 5.5 and 18.4 +/- 6.8 pg.ml-1 (P < 0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.

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)

Using cats with chronically implanted brain electrodes, we have compared the effects of propofol on CNS electrical activities with those of thiopentone. Ten cats were allocated to receive either propofol (n = 5) or thiopentone (n = 5). Cats were anaesthetized initially with 4% halothane in oxygen. The trachea was intubated and the lungs ventilated mechanically. A femoral artery and a vein in a forepaw were cannulated for arterial pressure monitoring and fluid infusion. After the inspired concentration of halothane was maintained at 0.5%, EEG in the cortex, the amygdala and the hippocampus, somatosensory evoked potential (SEP) and reticular multi-unit activity (R-MUA) were recorded. Incremental doses of propofol or thiopentone were administered i. v. at 5-min intervals during 0.5% halothane anaesthesia. The cumulative doses of propofol and thiopentone were 2, 5, 10 and 20mg kg−1, and 4, 10, 20 and 40 mg kg−1 respectively. Arterial pressure was maintained in excess of 100 mm Hg systolic by infusion of phenylephrine. All cats in the propofol group survived, but two in the thiopentone group died after the adminstration of thiopentone 40mg kg−1 Changes observed in CNS activity were dose-related in all cases. The EEG changed with the increments of doses of propofol or thiopentone, from fast, small amplitude to complexes of fast and slow, large amplitude activities, burst suppression and flat EEG. SEP latency was prolonged by both agents: the peak latency of N1 changed from 15 (SD 2) ms to 20 (5) ms with propofol 20mg kg−1, and from 14 (1) ms to 27(2) ms with thiopentone 40 mg kg−1. SEP amplitudes were depressed by both agents: the amplitude of N1 was depressed by 70 (29) % with propofol 20 mg kg−1 and by 60 (33) % with thiopentone 40mg kg−1. The R-MUA also was depressed by both agents: 85 (4) % with propofol 20 mg kg−1 and 85 (8) % with thiopentone 40mg kg−1. The R-MUA was depressed to 50% of control by propofol 3.2 (1.6) mg kg−1 or thiopentone 6.7 (5.0) mg kg−1. These depressive actions on the EEG, SEP and R-MUA induced by propofol were similar to those induced by twice the equivalent doses of thiopentone on an mg kg−1 basis. These results indicate that propofol has the same simple depressant effects as thiopentone on CNS electrical activity.

The effects of halothane, isoflurane, and enflurane on background neuronal activity and reactive capability in the central nervous system were studied in cats. The background neuronal activity was assessed by midbrain reticular cell firing, which was measured by the method of multi-unit activity, and the EEG in the cortex, amygdala, and hippocampus. The reactive capability was assessed by evoked responses in the visual neuronal pathway. All anaesthetics studied suppressed reticular cell firing in a dose-dependent manner, and the suppression by halothane (43.8 +/- 10.3% of control, mean +/- SD) was less than isoflurane (66.5 +/- 5.8%, P0.01) and enflurane (73.1 +/- 8.8%, P0.05) at 1 MAC. Spontaneous EEG spikes developed at 4.8% isoflurane and 3.6% enflurane anaesthesia. Phasic activation of reticular cell firing was associated with EEG spikes during isoflurane and enflurane anaesthesia, and the activation during enflurane anaesthesia was greater than during isoflurane anaesthesia (P0.01). Photic stimulation provoked EEG spikes and repetitive stimulation induced seizure activity only at 3.6% enflurane anaesthesia. Halothane and isoflurane suppressed stimulation induced responses in the visual neuronal pathway. The amplitudes of N1 in visual cortical evoked responses induced by photic stimulation were suppressed to 70.1 +/- 24.5% of control at 2.4% halothane and 39.3 +/- 27.3% at 4.8% isoflurane. Enflurane, at 3.6%, augmented the evoked response induced by photic stimulation (398.4 +/- 83.0% of control in the amplitude of N1). These results indicate that all the agents studied had suppressive actions on background neuronal activity in the order halothaneisoflurane = enflurane. The effects on reactive capability were divergent among agents, e.g., enflurane enhanced, halothane suppressed, and the actions of isoflurane were intermediate. We conclude that the anaesthetic effects on background activity and on reactive capability are divergent and that suppression of reactive capability is a factor in determining the ease of clinical application of the anaesthetics.

We investigated the EEG responses in 17 patients during induction of anaesthesia with vital capacity breaths of 4% halothane. The control alpha activity changed to a low voltage, 5-25 muV, fast, 20-28 Hz activity at the time of loss of consciousness at 78 (SD 27) s and typical spindle bursts (20-75 muV, 12-15 Hz) developed at 223 (51) s. All patients remained haemodynamically stable. This sequence of EEG changes was similar to that observed during induction with the conventional method of normal tidal volume breathing and a gradual increase of the inspired concentration of halothane.

The in vitro effects of halothane on the potassium-stimulation-induced efflux of [3H]D-aspartate in rat cerebral cortex slices were studied. The slices were initially incubated with Krebs-Ringer's solution containing [3H]D-aspartate, a putative excitatory transmitter. The slices were then stimulated with high concentrations of K+ in the presence and absence of halothane, and the efflux was measured using a scintillation counter. Halothane, 1% and 2%, had little effect on the potassium-stimulation-induced efflux, but that of 4 and 8% increased the efflux significantly. The spontaneous efflux was unaffected by all concentrations of halothane studied. The control study of pentobarbital, in the concentration of 0.05 to 1.00 mmol/l, reduced the efflux in a dose-related manner. These findings indicate that the release of an excitatory transmitter, aspartate, may not be involved in the mechanism of halothane anaesthesia.

The effect of nitrous oxide on the activity of the somatosensory system was studied in cats with brain electrodes implanted chronically. The electrodes were implanted in the primary somatosensory cortex, cortical somatosensory radiation, medial lemniscus and midbrain reticular formation. Alterations in the excitability of the primary sensory pathway were assessed by the changes of the input to and output from these brain areas: the response in the medial lemniscus to the stimulation of the skin represented the input to the thalamic relay nucleus and the response recorded in the cortical sensory radiation represented the output from the thalamic relay nucleus. The concentrations of nitrous oxide studied were 50% and 75% in oxygen, and the drug effect was concentration-related. The cortical response to peripheral stimulation was suppressed in amplitude by more than 40% of the control with 75% nitrous oxide, and the response in the cortical radiation was suppressed by 20% of the control with the same dose of nitrous oxide. The response in the cortical radiation to stimulation of the medial lemniscus was suppressed by 20% of the control and the postsynaptic component of the cortical response to the stimulation of the medial lemniscus was suppressed by more than 50% of the control. The multi-unit activity of the brainstem reticular formation was enhanced by nitrous oxide in a dose related manner. The excitability of the thalamic relay nucleus and the primary somatosensory cortex was suppressed by natural slow wave sleep when the reticular multi-unit activity was suppressed, and they were enhanced by paradoxical phase of sleep when the reticular multi-unit activity was enhanced. These findings indicated that the degree of suppression of excitability by nitrous oxide is similar in both the thalamic relay nucleus and sensory cortex, and its action on the brain stem reticular formation is different from that on the primary sensory system. The suppression of sensory functions shown in the present study provides a certain clue to the understanding of the neural basis that though nitrous oxide does not produce deep surgical anesthesia, it does induce potent analgesia and sedation during surgery.

Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo.Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5-10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1-1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values.Bleeding time was increased from the preanesthetic value of 2.07 +/- 0.82 min to 2.83 +/- 0.93 min (n = 15) in the sevoflurane group (P0.01) but was not significantly altered in the isoflurane group.Sevoflurane alters bleeding time in the clinical situation.

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

We have compared the rapidity and quality of recovery after sevoflurane anaesthesia with those after halothane anaesthesia. Thirty unpremedicated paediatric outpatients undergoing pulsed-dye laser therapy for port-wine stains were allocated randomly to receive either halothane or sevoflurane anaesthesia. Each group received 60% nitrous oxide and 1.0-1.5 MAC of volatile agent in oxygen for approximately 40 min. Patients receiving sevoflurane exhibited more rapid emergence and a significantly shorter postoperative recovery time compared with those receiving halothane. No major adverse effects were encountered in each group. These results suggest that sevoflurane anaesthesia is preferable to halothane anaesthesia for paediatric ambulatory patients.

We have investigated the effects of isoflurane on receptor-operated Ca2+ channels (ROC) in vascular smooth muscle. In isolated rat thoracic aortic rings denuded of endothelium, the effects of isoflurane on phenylephrine-induced contraction and Ca2+ influx were evaluated in the presence of supramaximal doses of nifedipine or verapamil. Under isometric tension recording, the aortic rings were precontracted by phenylephrine 300 nmol litre-1 and exposed to 1.2%, 2.3% or 3.5% isoflurane. Phenylephrine-induced precontraction was enhanced with 2.3% isoflurane by mean 8.1 (SD 9.3)% (P < 0.05 vs 0% isoflurane). The constrictor effect of 2.3% isoflurane was not inhibited by depletion of intracellular Ca2+ stores with ryanodine 20 mumol litre-1, but was abolished in a Ca(2+)-free solution or by SK&F 96,365 30 mumol litre-1, an ROC blocker. Isoflurane-induced contraction was accompanied by increased intracellular free Ca2+ concentration, monitored using fura PE3. Unidirectional 45Ca2+ influx measurement in phenylephrine-stimulated aortic strips revealed that the mean amount of Ca2+ influx was significantly (P < 0.05) enhanced by 1.2% and 2.3% isoflurane, which were 117.1% and 119.7% of control values, respectively. Our results strongly suggest that isoflurane enhanced Ca2+ influx through ROC that had been submaximally activated by phenylephrine.

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.

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.

Objectif: Presenter une rare observation de reaction anaphylactoide au maltose. Elements cliniques : Un homme de 28 ans a subi une cure bilaterale de hernie inguinale sous rachianesthesie a la dibucaine. A la fin de l'intervention, il a presente un erytheme generalise et un collapsus circulatoire apres l'administration d'acetate de Na contenant du maltose a 5% iv. La reaction a ete traitee avec 32 mg d'ephedrine et 250 mg de methylprednisolone iv avec une perfusion rapide de 1 000 ml d'une solution de Ringer avec acetate. Lintradermoreaction etait positive aux solutions de maltose. Conclusion : Les element cliniques et les epreuves cutanees suggerent une reaction anaphylactoide au maltose. Le maltose est un dissacharide (PM : 342) provenant de l'amidon et du glycogene. Au Japon, on administre souvent des solutions de maltose comme sources d'hydrates de carbone. Des epreuves supplementaires sont necessaires pour confirmer l'action antigenique du maltose.

We have studied the effects of barbiturates on vascular smooth muscle tension and cytosolic calcium concentrations ([Ca2+]i) in endothelium-denuded rat aortic rings, preloaded with fluo-3. Changes in [Ca2+]i were estimated by the fluorescence intensity of the calcium-bound form of fluo-3. In aortic rings under basal conditions, thiobarbiturates (thiopentone and thiamylal 100-300 mumol litre-1) increased [Ca2+]i, concomitantly with an increase in tension, although oxybarbiturates (pentobarbitone and secobarbitone up to 300 mumol litre-1) had no effect. Thiopentone (300 mumol litre-1)-induced increases in tension and fluorescence intensity were mean 25.1 (SD 3.2)% and 55.0 (6.0)%, respectively, of those induced by KCl 30 mmol litre-1 (n = 8, each). In KCl (30 mmol litre-1)-precontracted aortic rings, thiopentone decreased tension without reduction of [Ca2+]i, whereas pentobarbitone decreased tension and [Ca2+]i, KCl (30 mmol litre-1)-induced contraction was suppressed by pretreatment with all barbiturates (100-300 mumol litre-1); thiopentone 300 mumol litre-1 suppressed contraction to 64.8 (2.5)% (n = 6) and pentobarbitone 300 mumol litre-1 to 57.5 (2.2)% (n = 9). However, the increase in [Ca2+]i was suppressed by oxybarbiturates (pentobarbitone 300 mumol litre-1 to 77.9 (5.2) %; n = 9), but not altered by thiobarbiturates. These results suggest that thiobarbiturates and oxybarbiturates affect vascular smooth muscle differently and that the affected site in thiobarbiturate-induced vasodilatation is distal to regulation of [Ca2+]i.

Previous studies have failed to demonstrate a block of the endocrine response to upper abdominal surgery by thoracic epidural analgesia. To clarify the bases for this failure, we compared the effects of epidural analgesia of different dermatome levels up to C8-T2 or C3-4. The patients who received general anesthesia alone showed significant increases of adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) immediately after skin incision. The patients with C8-T2 blocked developed significant increases in these hormones, not after the skin incision, but after the intraabdominal procedure. Of the eight patients with C3-4 block, six developed no such responses throughout the study period. The responses of oxytocin (OXT) and prolactin (PRL) were more susceptible to epidural analgesia and were blocked at the C8-T2 level. Growth hormone (GH) showed no correlation with surgical procedures and epidural block. These findings indicate that the nociceptive neural information during upper abdominal surgery is conveyed by the sensory fibers included in both the thoracic and lumbar spinal nerves that innervate the abdominal wall and the intraabdominal viscera, and by the phrenic nerves that innervate the diaphragm. The rationale for postulating the involvement of the phrenic nerves can be referred to the embryonal descent of the diaphragm from the C3-5 myotomes that serves as the upper wall of the abdominal cavity.

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.

Since volatile anesthetics, barbiturates, and local anesthetics have been reported to inhibit endothelium-dependent relaxation, we hypothesized that any drug with anesthetic action would suppress this relaxation. In the present study, using rat thoracic aortae, we attempted to determine whether nonbarbiturate intravenous anesthetics, including midazolam, propofol, and ketamine, suppress endothelium-dependent relaxation, and to clarify the mechanism(s) involved. Acetylcholine-induced, endothelium-dependent relaxation was significantly attenuated by propofol and ketamine, but was unaffected by midazolam. Sodium nitroprusside (SNP)-induced relaxation was attenuated by propofol, but not by midazolam or ketamine. The acetylcholine-stimulated 3',5'-cyclic guanosine monophosphate (cGMP) level was reduced by pretreatment with propofol and ketamine but not by midazolam, and that stimulated by SNP was reduced by propofol but not by ketamine or midazolam. We conclude that propofol and ketamine suppress endothelium-dependent relaxation, whereas midazolam has no influence. Moreover, the suppressive effect of ketamine on endothelium-dependent relaxation is mediated by suppression of nitrous oxide (NO) formation, whereas that of propofol may be mediated at least partly by suppression of NO function.

Sevoflurane, a new inhalational anesthetic, is metabolically broken down into several decomposition products in the presence of CO2 absorbents. One of the products, CF2=C (CF3) OCH2F (compound A), which appears to be the most toxic, was quantitated in 20 surgical patients subjected to more than 3 h of anesthesia using a low-flow anesthesia circuit. To minimize the variables in the reaction velocity between sevoflurane and the CO2 absorbents, we maintained the sevoflurane concentration at 2%. Wakolime-A, one type of soda lime, resulted in the highest increase in compound A concentration. The peak concentration was 27.1±3.1 ppm, less than one-tenth of the LC50 (50% lethal concentration) of compound A, which was previously reported as 420 or 400 ppm in rats. We also measured the temperature in CO2 absorbents, which had been reported to influence compound A production. The elevation in the temperature was 27.9±1.3°C in Wakolime-A, 29.4±8.4°C in Baralyme, and 31.0±5.0°C in Sodasorb II. Further studies are needed to assess the safety and efficacy of sevoflurane.

In a previous study, we demonstrated that halothane and isoflurane inhibit binding of thromboxane A2 to its receptors on human platelets and thus inhibit prostanoid-induced aggregation strongly. The aim of this study was to determine whether volatile anaesthetics inhibit prostanoid-induced vasoconstriction preferentially. Rat isolated aortic rings were mounted in organ baths and their isometric tension was measured. They were contracted with STA2 (a stable thromboxane A2 analogue), prostaglandin F2 alpha (PGF2 alpha), phenylephrine, and 20 mM KCl, and then exposed to halothane (0.5-3%), isoflurane (0.5-3%), and sodium nitroprusside (SNP, 10(-9)-3 x 10(-7) M). Halothane (2-3%) and isoflurane (2-3%) induced greater relaxation of aortic rings precontracted with STA2 and PGF2 alpha than of those precontracted with phenylephrine (P0.01). Halothane induced greater relaxation of rings precontracted with KCl than phenylephrine only at 3%, whereas isoflurance relaxed rings precontracted with KCl more than those with phenylephrine at 0.5, 2 and 3% (P0.05). In contrast, SNP relaxed rings precontracted with PGF2 alpha. KCl and phenylephrine equally, but induced smaller relaxations of those precontracted with STA2 (P0.05). We conclude that halothane and isoflurane inhibit prostanoid-induced vasoconstriction preferentially, possibly by interacting with prostanoid receptors.

The inhibitory effects of volatile and local, but not intravenous, anesthetics on endothelium-dependent relaxations of blood vessels have been demonstrated in vitro by several investigators. The aim of this study was to determine the effects of barbiturates on endothelium-dependent arterial relaxation and elucidate the mechanism(s) responsible. Canine mesenteric arteries and rat aortae were isolated, and tension changes in helical strips were recorded. Endothelium-dependent relaxations elicited by acetylcholine and bradykinin in canine mesenteric arteries, and those by acetylcholine in rat aortae, were significantly attenuated by thiopental (3 x 10(-4) M) pretreatment. Sodium nitroprusside (SNP)-induced, endothelium-independent relaxations were significantly attenuated by thiopental (10(-4)-3 x 10(-4) M). The effects of pentobarbital were less marked than those of thiopental. Acetylcholine (10(-5) M)-stimulated levels of 3',5'-cyclic guanosine monophosphate (cGMP) in rat aortae were reduced significantly by thiopental and pentobarbital (both 10(-3) M), and SNP (3 x 10(-7) M)-stimulated levels were reduced by thiopental (3 x 10(-4)-10(-3) M) and pentobarbital (10(-3) M). We conclude that barbiturates inhibit cGMP-mediated endothelium-dependent and independent arterial relaxations. Inhibition of endothelium-dependent relaxation by barbiturates may be mediated by their effects on vascular smooth muscle itself and not on endothelium.

To evaluate the effect of combined intravenous administration of the calcium antagonists, nicardipine and diltiazem, on the circulatory responses to tracheal intubation, the mean arterial pressure (MAP) and rate pressure product (RPP) in response to laryngoscopy following tracheal intubation were compared in patients receiving saline placebo or nicardipine 10 μg·kg−1 and diltiazem 0.1 mg·kg−1 60 s before the initiation of laryngoscopy. Each group was comprised of ten patients undergoing elective surgery. The patients receiving saline showed a significant increase in MAP and RPP associated with tracheal intubation. However, these increases were significantly attenuated (P

In order to develop a new technique for the measurement of local cerebral blood flow (CBF), the deuterium chemical shift imaging (2H-CSI) technique, an application of in vivo nuclear magnetic resonance (NMR), was used for the estimation of cerebral perfusion in rabbit infarction model. The 2H chemical shift images of rabbit brain were obtained every 30 seconds before and after intravenous injection of deuterated saline. The changes in 2H NMR signal intensity documented that the cerebral perfusion in the damaged area due to infarction decreased obviously compared to that in the intact area. These findings indicate that the 2H-CSI technique can be applied to the measurement of local CBF. The readily availability and limited toxicity of deuterated water may make possible to use this method in clinical cases.

We have studied the effects of flumazenil on sleep time and EEG in rats anaesthetized with 1.5% halothane, propofoi 20 mg kg−1, thiamylal 30 mg kg−1, or combinations of diazepam 5 mg kg−1 and anaesthetic agents. We also studied the effects of flumazenil 0.3, 3 and 30 mg kg−1 on behaviour and EEG. Flumazenil 0.3 and 3 mg kg−1 alone had no effect on behaviour or EEG, but flumazenil 30 mg kg−1 had depressive effects similar to those of diazepam on behaviour and EEG. Flumazenil 0.3, 3 and 30 mg kg−1 i.v., antagonized the effects of diazepam 10 mg kg−1 i.v. on behaviour and EEG. Flumazenil had no antagonistic effect on sleep time induced by anaesthetic agents, but flumazenil 30 mg kg−1 potentiated propofol-induced anaesthesia. Flumazenil did not affect anaesthesia-induced EEG changes. Diazepam 5 mg kg−1 potentiated anaesthesia. Flumazenil antagonism of diazepam potentiation varied with anaesthetic agent: flumazenil 0.3 mg kg−1 antagonized diazepam action in halothane anaesthesia, but 30 mg kg−1 was required in propofoi anaesthesia; this large dose was insufficient in thiamylal anaesthesia.

We have measured the direct effects of propofol 10(-7)-10(-4) mol litre-1 on isolated canine cerebral, coronary, mesenteric, femoral and renal arteries. In arterial strips precontracted submaximally with potassium chloride or prostaglandin F2 alpha (PGF2 alpha), propofol induced further contractions at low concentrations (10(-6)-10(-5) mol litre-1) and relaxation at high concentrations (10(-4) mol litre-1). Intrafat, which contains soya bean oil, egg phosphatide and glycerol in similar concentration to the emulsion formulation of propofol, had a small relaxant effect at a concentration corresponding to propofol 10(-4) mol litre-1. In humans, clinically relevant plasma concentrations of propofol have been reported to be 1-5 x 10(-5) mol litre-1, 97-99% of which is bound to plasma proteins. Therefore, the results obtained in this study demonstrated that clinically relevant concentrations of propofol did not have direct vasodilator effects.

Maintenance of enough organ blood flow and appropriate oxygen supply/demand balance is a very important component of anesthetic management of major surgeries. Recently developed venous oxygen saturation monitoring is useful to estimate the enough organ perfusion, and more, can provide us continuous information.

The effects of halothane on diazepam binding to the rat cerebral synaptic membranes were investigated. Halothane at the concentrations of 0.63, 1.3 and 4.1 mmol/l increased the binding by 12, 23 and 33%, respectively, compared to the control in the absence of halothane. The increments were dependent on the presence of Cl-. The findings indicate that halothane and diazepam have an interaction at receptor level.

In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2 alpha (PGF2 alpha), the addition of pentobarbital (10(-5) to 10(-3) mol.l-1) caused dose-related relaxation, whereas thiamylal and thiopental in a low concentration (10(-5) to 10(-4) mol.l-1) caused further contraction and in a high concentration (10(-3) mol.l-1) profound relaxation. Thiobarbiturate-induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2 alpha. In cerebral and mesenteric arteries exposed to Ca(++)-free media for 60 min and treated with KCl or PGF2 alpha, reintroduction of Ca++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca(++)-induced persistent contraction was attenuated by pretreatment with pentobarbital (10(-4) to 10(-3) mol.l-1) and thiamylal (10(-3) mol.l-1); the attenuation was greater in arteries treated with KCl than with PGF2 alpha. The Ca(++)-induced contractions of mesenteric artery treated with PGF2 alpha were potentiated by 10(-4) mol.l-1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl-induced depolarization than by a stimulation of PGF2 alpha receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor-operated Ca++ channel for PGF2 alpha.

Time required for the cannulation of right internal jugular vein (IJV) under ultrasonographic guidance with a Valsalva maneuver was investigated in surgical patients. The degree of distension of the IJV and the changes in blood pressure (BP) during the maneuver were also examined. The required time for the cannulation was 11 +/- 5 sec (mean +/- SD, n = 21), and there was no failure in the cannulation. The mean BP decreased significantly during the maneuver, while the vessels enlarged approximately twofold, which facilitated the cannulation. The decrease in BP and the enlargement of the vessels during a Valsalva maneuver were confirmed in the left side, which indicated the feasibility of left IJV cannulation under ultrasonographic guidance.

Responses to thiamylal and thiopental were compared in helical strips of rat thoracic aortas of different ages (5-6, 10-12 and 20-22 weeks old), precontracted partially with phenylephrine or prostaglandin F(2alpha) (PGF(2alpha)). Thiamylal and thiopental, in concentrations of 3 x 10(-5) to 10(-4) M, produced a dose-dependent relaxation in aortas at 5-6 weeks of age, no significant change of tension in those at 10-12 weeks of age, and a marked constriction in those at 20-22 weeks of age. These thiobarbiturates, in a high concentration of 10(-3) M, produced a profound relaxation in aortas at any age studied. It is concluded that the responses to thiobarbiturates of thoracic aorta precontracted with phenylephrine or PGF(2alpha) alter with age.

The anticonvulsant action of nitrous oxide and its time course were studied in rats. Bicuculline, a GABA-receptor antagonist, was administered intravenously at a rate of 0.2 mg.kg(-1).min(-1) during exposure to air (n = 60) or 75% nitrous oxide in oxygen (n = 80). The convulsant dose of bicuculline was determined. The rats were divided into subgroups according to the duration of exposure to air or nitrous oxide, from 0 to 120 min at 15 min intervals. Although the convulsant dose of bicuculline was consistent in the air group (1.03 +/- 0.06 mg.kg(-1), mean +/- SEM), it showed two peaks at 30- and 90 min exposures to nitrous oxide. The threshold dose in the nitrous oxide group was significantly higher than in the air group at only 15- and 30 min exposures (1.50 +/- 0.16, 2.15 +/- 0.25 mg.kg(-1), respectively, P0.05). We conclude that nitrous oxide has an anticonvulsant action against bicuculline-induced seizure, and that a cyclic nature exists in its action.

The internal jugular vein (LTV) can provide an extremely reliable site for correct placement of central venous catheter. The average success rate using this approach is more than 95 percent l. However, percutaneous cannulation of the IJV has not been recommended in pediatric age group because of the low success rate in children under age 2 • Monitoring of central venous pressure (CVP) is quite useful in the management of children undergoing major surgery, so that a safe and sure approach to percutaneous cannulation is mandatory. We describe an improved technique for the .percutaneous IJV cannulation which, in our experience, has proven very reliable when attempting to identify the IJV.

Although a large number of studies on pulmonary aspiration have been reported [1,2] and precautions are being taken to prevent this complication [3], all of these studies and precautions involve patients with a normal upper gastrointestinal (GI) tract. As far as we know, there is currently no documentation in the literature, including major textbooks, of studies investigating whether standard precautions are sufficient to prevent pulmonary aspiration in patients with a history of esophageal or gastric surgery. Here we would like to report a case of pulmonary aspiration in a postesophagectomy patient during induction of anesthesia, because this case is valuable to clarify the risks of aspiration in patients who have undergone upper GI tract surgery.

To investigate the clinical significance of endothelin (ET), a potent and long-acting vasoconstrictor peptide in anesthesia and surgery, we measured plasma ET-like immunoreactivity (ET-LI) levels by using radioimmunoassay in patients undergoing various kinds of surgery under general anesthesia. No significant changes in plasma ET-LI levels were observed in patients undergoing relatively minor surgery under general anesthesia with nitrous oxide and halothane (n=6), enflurane (n=6), or isoflurane (n=5). Although plasma ET-LI levels after surgery in patients undergoing total knee replacement (12.4±0.9 [mean±SEM] pg/mL, n=7), hysterectomy (11.4±0.6 pg/mL, n=8) or cholecystectomy (14.8±1.2 pg/mL, n=9) were no different from those before surgery, plasma ET-LI levels after surgery in patients undergoing gastrectomy (20.4±1.9 pg/mL, n=15), esophagectomy (24.7±2.5 pg/mL, n=12), hepatectomy (27.5±3.4 pg/mL, n=12), or heart surgery (43.1±4.1 pg/mL, n=18) were higher than those before surgery (P