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Isoflurane
Terms modified by Isoflurane Selected AbstractsXenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010M. HEIN Background: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate. Methods: The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were assessed in a porcine model (n=36) using the conductance catheter technique, and the expression of the type B natriuretic peptide (BNP) gene was measured. The animals underwent 90 min of right ventricular ischemia followed by 120 min of reperfusion. A barbiturate-anesthetized group was included as a control. Results: Cardiac output was compromised in unprotected animals during ischemia by 33±18% and during reperfusion by 53±17%. This was mainly due to impaired contractility in the left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase in stiffness and resulted in a higher preload. In contrast, xenon increased the right ventricular afterload, which was compensated by an increase in contractility. Its effects on diastolic function were less pronounced. Upregulation of BNP mRNA expression was impeded in the remote area of the LV by both isoflurane and xenon. Conclusions: Xenon and isoflurane demonstrated equipotent effects in preventing the hemodynamic compromise that is induced by right ventricular ischemia and reperfusion, although they acted through somewhat differential inotropic and vasodilatory effects. [source] Isoflurane attenuates pulmonary interleukin-1, and systemic tumor necrosis factor-, following mechanical ventilation in healthy miceACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009M. VANEKER Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. Methods: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH2O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. Results: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1, was found compared with non-ventilated control mice. Plasma: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-, was found compared with non-ventilated control mice. Conclusions: The present study is the first to show that isoflurane attenuates the pulmonary IL-1, and systemic TNF-, response following MV in healthy mice. [source] Isoflurane enhances spontaneous Ca2+ oscillations in developing rat hippocampal neurons in vitroACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009Q. XIANG Background: During the nervous system development, spontaneous synchronized Ca2+ oscillations are thought to possess integrative properties because their amplitude and frequency can influence the patterning of neuronal connection, neuronal differentiation, axon outgrowth, and long-distance wiring. Accumulating studies have confirmed that some drugs such as volatile anesthetic isoflurane produced histopathologic changes in the central nervous system in juvenile animal models. Because the hippocampus plays an important role in learning and memory, the present work was designed to characterize the Ca2+ oscillations regulated by volatile anesthetic isoflurane in primary cultures of developing hippocampal neurons (5-day-cultured). Methods: Primary cultures of rat hippocampal neurons (5-day-cultured) were loaded with the Ca2+ indicator Fluo-4AM (4 ,M) and were studied with a confocal laser microscope. Results: Approximately 22% of 5-day-cultured hippocampal neurons exhibited typical Ca2+ oscillations. These oscillations were dose-dependently enhanced by isoflurane (EC50 0.5 MAC, minimum alveolar concentration) and this effect could be reverted by bicuculline (50 ,M), a specific ,-aminobutyric acid (GABAA) receptor antagonist. Conclusion: Unlike its depressant effect on the Ca2+ oscillations in adult neurons in previous researches, isoflurane dose-dependently enhanced calcium oscillations in developing hippocampal neurons by activating GABAA receptors, a major excitatory receptor in synergy with N -methyl- d -aspartate receptors at the early stages of development. It may be involved in the mechanism of an isoflurane-induced neurotoxic effect in the developing rodent brain. [source] Isoflurane exerts a short-term but not a long-term preconditioning effect in neonatal rats exposed to a hypoxic-ischaemic neuronal injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009N. SASAOKA Background: Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury. Methods: Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI. Results: Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI. Conclusions: Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection. [source] Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cellsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009G.-J. WU Background: It has been proposed that the volatile anesthetic isoflurane induces neuroprotection and that the endogenous opioid peptide dynorphin induces neurocytotoxicity in cells. The levels of dynorphin are often significantly elevated in neuropathophysiological conditions, and dynorphin can directly induce toxicity. However, the neuroprotective effects of isoflurane on dynorphin-induced cytotoxicity are still unclear. Methods: In order to determine the effect of isoflurane on dynorphin-induced cytotoxicity in neuronal cells, we have designed a device wherein cultured human neuroblastoma SH-SY5Y cells can be exposed to isoflurane. Fully differentiated SH-SY5Y cells were obtained by treating the cells with retinoic acid for 6 days. We examined SH-SY5Y cell survival, apoptosis, and antiapoptotic protein expression by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain, and Western blot analysis, respectively. Results: After 16 h of dynorphin (10 ,M) treatment, the SH-SY5Y cells showed significant cytotoxicity, apoptosis, and downregulation of the antiapoptotic Bcl-2 protein expression. These effects of dynorphin were significantly inhibited by isoflurane exposure for 32 h [pretreatment for 16 h and posttreatment (after dynorphin treatment) for 16 h]. Conclusion: Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption. [source] Isoflurane-induced depolarization of neural mitochondria increases with ageACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009RAVI BAINS Background and objectives: The mitochondrial membrane potential (,,m) drives the three fundamental functions of mitochondria, namely adenosine triphosphate (ATP) generation, Ca2+ uptake/storage, and generation/detoxification of ROS. Isoflurane depolarizes neural mitochondria. The sensitivity for general anesthetics increases with age, but the mechanism for this age-related sensitivity is still unknown. We compared the effect of isoflurane on [Ca2+]i and ,,m in isolated pre-synaptic terminals (synaptosomes) from neonatal, adolescent, and adult rats and the influence of interventions in the respiratory chain was assessed. Methods: Synaptosomes were loaded with the fluorescent probes fura-2 ([Ca2+]i) and JC-1 (,,m) and exposed to isoflurane 1 and 2 minimum alveolar concentration (MAC). The effect on the electron transport chain was investigated by blocking complexes I and V. Results: In neonatal rats isoflurane had no significant effect on ,,m. In adolescent and adult synaptosomes, however, isoflurane 1 and 2 MAC decreased ,,m. Isoflurane 2 MAC increased [Ca2+]i in neonatal and adolescent rats, but not in adult synaptosomes. In Ca2+ -depleted medium, isoflurane still decreased ,,m, while [Ca2+]i remained unaltered. By blocking complex V of the respiratory chain, the isoflurane-induced mitochondrial depolarization was enhanced in all age groups. Blocking complex I depolarized the mitochondria to the same extent as isoflurane 2 MAC, but without any additive effect. Conclusions: The depolarizing effect of isoflurane on neural mitochondria is more pronounced in the adolescent and adult than in neonatal synaptosomes. The increased mitochondrial sensitivity with age seems to be related to the reversed function of the ATP synthase of the electron transport chain. [source] Effects of isoflurane, pentobarbital, and urethane on apoptosis and apoptotic signal transduction in rat kidneyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2006N. Aravindan Background:, Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Anesthetic agents have been shown to modulate apoptotic signal transduction in various tissues. We examined the effects of 6 h of different general anesthetic techniques on renal cell apoptosis in rat kidneys. Methods:, Twenty-one male Sprague,Dawley rats were randomly allocated into four groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii) inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv) intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction of anesthesia. Results:, Apoptosis was assessed by terminal deoxynucleotidyl transferase-fluorescein end-labeling analysis. RNA was extracted from the left kidney to probe cDNA microarrays. Gene expression was measured as a percentage of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down-regulated more genes (85) than pentobarbital (74) and urethane (12). These anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30 pentobarbital- and 4 urethane-modulated genes. Conclusion:, Our results suggest that general anesthetic drugs have an effect on renal cell apoptosis and apoptotic signal transduction, and thus may potentially affect the risk of subsequent acute renal failure. [source] Volatile anaesthetics depolarize neural mitochondria by inhibiton of the electron transport chainACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2006R. Bains Background:, The mitochondrial membrane potential (,,m) controls the generation of adenosine triphosphate (ATP) and reactive oxygen species, and sequesteration of intracellular Ca2+[Ca2+]i. Clinical concentrations of sevoflurane affect the ,,m in neural mitochondria, but the mechanisms remain elusive. The aim of the present study was to compare the effect of isoflurane and sevoflurane on ,,m in rat pre-synaptic terminals (synaptosomes), and to investigate whether these agents affect ,,m by inhibiting the respiratory chain. Methods:, Synaptosomes were loaded with the fluorescent probes JC-1 (,,m) and Fura-2 ([Ca2+]i) and exposed to isoflurane or sevoflurane. The effect of the anaesthetics on the electron transport chain was investigated by blocking complex I and complex V. Results:, Isoflurane 1 and 2 minimum alveolar concentration (MAC) decreased the normalized JC-1 ratio from 0.92 ± 0.03 in control to 0.86 ± 0.02 and 0.81 ± 0.01, respectively, reflecting a depolarization of the mitochondrial membrane (n = 9). Isoflurane 2 MAC increased [Ca2+]i. In Ca2+ -depleted medium, isoflurane still decreased ,,m while [Ca2+]i remained unaltered. The effect of isoflurane was more pronounced than for sevoflurane. Blocking complex V of the respiratory chain enhanced the isoflurane- and sevoflurane-induced mitochondrial depolarization, whereas blocking complex I and V decreased ,,m to the same extent in control, isoflurane and sevoflurane experiments. Conclusions:, Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre-synaptic mitochondria through inhibition of the electron transport chain, although isoflurane seems to inhibit mitochondrial function more significantly than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause ATP synthase reversal. [source] Effect of isoflurane on monocyte adhesion molecule expression in human whole blood,ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2003L. W. De Rossi Background: Recruitment of monocytes to inflamed tissue is a crucial step in the acute inflammatory reaction. Adherence of monocytes to endothelial cells followed by transmigration depends on monocyte surface adhesion molecules, inflammatory cytokines and chemoattractant chemokines. In the present study, we determined the effect of isoflurane on monocyte adhesion receptor expression in vitro. Methods: Citrated whole blood was incubated for 60 min with either 0.5 or 1 MAC isoflurane. In unstimulated blood samples and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) monocyte cell-surface expression of the selectins PSGL-1 and L-selectin, and the ,2 -integrins CD11a and CD11b were evaluated by flow cytometry. Results: Isoflurane reduced significantly the expression of PSGL-1 on unstimulated monocytes, whereas the remaining selectins and ,2 -integrins were not affected. At both concentrations, the FMLP-induced removal of PSGL-1 from the monocyte surface was increased. Furthermore, at 1 MAC isoflurane the FMLP-induced increase in CD11a expression was significantly inhibited. The surface expression of L-selectin and CD11b was not affected following exposure to isoflurane. Conclusion: Isoflurane increases the removal of the selectin PSGL-1 from the monocyte surface. Since PSGL-1 is important during the initial step of monocyte adhesion to endothelial P-selectin, the decrease in monocyte surface PSGL-1 may have profound effects on monocyte,endothelial interactions. Furthermore, the effects of isoflurane on monocyte adhesion molecule expression are different from those reported for neutrophils. [source] Effects of isoflurane on nitric oxide metabolism and oxidant status of guinea pig myocardiumACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2001. Durak Background: Volatile anesthetics (VAs) have been shown to enhance myocardial recovery during reperfusion, the mechanism of which has not been clarified yet. It has been supposed that this effect of VAs may appear through antioxidative mechanisms. Methods: Thirty guinea pigs were used in the study. There were three groups with 10 animals in each: I , control, II , isoflurane+oxygen and III , oxygen. Isoflurane (2.0% v/v) and oxygen (100%) mixture was given to the animals via a face mask in the isoflurane+oxygen group at the rate of 2 l per min for 30 min a day for three consecutive days. In the oxygen group, oxygen alone (100%) was given under the same conditions as in the isoflurane+oxygen group. At the end of the experiments, the animals were killed and their hearts were removed. In the heart tissues, nitric oxide synthase (NOS) activity, nitric oxide (NO) pool (NO,+NO2,) and malondialdehyde (MDA) levels were measured. Results: NOS activity was found to be higher and the NO pool lower in the isoflurane+oxygen group compared with those of control and oxygen groups. In the oxygen group, MDA level was found to be higher compared to the other groups. There was, however, no significant difference between MDA levels of the control and isoflurane+oxygen groups. Conclusion: Our results suggest that isoflurane prevents peroxidation reactions in heart tissue, possibly by scavenging toxic oxygen radicals produced under hyperoxygenation conditions as occurs with general anesthesia. [source] Does halothane or isoflurane affect hypoxic and post-hypoxic vascular response in rabbit aorta?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2000E. Haddad Background: Halothane and isoflurane affect differently endothelium-dependent and -independent vasorelaxation at 95% O2. In addition, hypoxic vascular response might involve endothelium-dependent and -independent mechanisms. Therefore, we investigated, in rabbit aortic rings, 1) the influence of halothane and isoflurane on vasodilation at 95% O2 and on hypoxic-induced vasorelaxation at 0% O2 and 2) the influence of halothane and isoflurane on endothelium-dependent and -independent post-hypoxic vascular response. Methods: Endothelium-intact and endothelium-denuded rabbit aortic rings were used. Phenylephrine precontracted rings were exposed, at 95% O2, to acetylcholine (ACh, 10,9 to 10,4 M) or sodium nitroprusside (SNP, 10,9 to 10,4 M) in the presence or absence of anaesthetic at 1 or 2 MAC. Precontracted rings were also exposed to an acute reduction in O2 from 95% to 0% followed by an acute reoxygenation with 95% O2 in the absence or presence of anaesthetic at 1 or 2 MAC. Results: At 95% O2, halothane decreased endothelium-dependent relaxation to ACh, while endothelium-independent relaxation to SNP was decreased only at 2 MAC. Isoflurane did not modify ACh- or SNP-induced relaxation. At 0% O2, neither halothane nor isoflurane altered the hypoxic vascular relaxation. Post-hypoxic response was not changed either. Conclusion: Our results indicate that halothane and isoflurane do not alter vascular hypoxic response in conductance arteries. [source] Isoflurane is associated with a similar incidence of emergence agitation/delirium as sevoflurane in young children , a randomized controlled studyPEDIATRIC ANESTHESIA, Issue 1 2007ROLAND RICHARD MEYER MD Summary Background:, Children may be agitated or even delirious especially when recovering from general anesthesia using volatile anesthetics. Many trials have focused on the newer agents sevoflurane and desflurane but for the widely used isoflurane little is known about its potential to generate agitation. We investigated the emergence characteristics of small children after sevoflurane or isoflurane with caudal anesthesia for postoperative pain control. Methods:, After institutional approval and parental consent, anesthesia was randomly performed with sevoflurane (n = 30) or isoflurane (n = 29) in children at the age of 3.8 ± 1.8 years during surgical interventions on the lower part of the body. After induction, all children received caudal anesthesia with bupivacaine (0.25%, 0.8 ml·kg,1). Postoperatively, the incidences of emergence agitation (EA) and emergence delirium (ED) were measured by a blinded observer using a ten point scale (TPS; EA = TPS > 5 ED = TPS > 7) as well as vigilance, nausea/vomiting and shivering. Results:, The two groups were comparable with respect to demographic data, duration of surgery and duration of anesthesia. There were also no differences in the period of time from the end of surgery until extubation, duration of stay in the PACU, postoperative vigilance and vegetative parameters. Incidence of EA was 30% (9/30) for sevoflurane and 34% (10/29) for isoflurane during the first 60 min in the PACU (P = 0.785). Likewise, the incidence of ED was not different between the groups (20% and 24%, respectively). Conclusions:, In our randomized controlled study, we found no difference in the incidence of EA or ED between sevoflurane and isoflurane. Therefore, the decision to use one or the other should not be based upon the incidence of EA or ED. [source] The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid ,-protein level in vivoANNALS OF NEUROLOGY, Issue 6 2008Zhongcong Xie MD Objective An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease,associated amyloid ,-protein (A,) in cultured cells. However, the in vivo relevance has not been addressed. Methods We therefore set out to determine effects of isoflurane on caspase activation and levels of ,-site amyloid precursor protein,cleaving enzyme (BACE) and A, in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction. Results Here we show for the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for 2 hours) leads to caspase activation and modest increases in levels of BACE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and A, up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the A, aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Interpretation Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation. Ann Neurol 2008 [source] Effects of Intrathecal Injection of Nicotine on the Analgesic Effects of Isoflurane in a Model of Inflammatory PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Wei Cheng After having established the mice model of analgesia by intraperitoneally injecting (i.p.) appropriate doses of isoflurane, nicotine, a neuronal nicotinic acetylcholine receptor agonist was intrathecally injected. The effects of isoflurane and nicotine on paw licking times and formalin-induced c-fos expression in the spinal cord dorsal horn were examined. Our correlative studies have shown that isoflurane can decrease the paw licking times and simultaneously suppress c-fos expression after injection of formalin in the mice. Nicotine can partially antagonize the effects induced by isoflurane above. Spinal neuronal nicotinic acetylcholine receptors may be important targets for the analgesic effects of isoflurane in formalin pain. [source] Influence of neurohumoral blockade on heart rate and blood pressure responses to haemorrhage in isoflurane anaesthetized ratsACTA PHYSIOLOGICA, Issue 3 2000UllmanArticle first published online: 24 DEC 200 Four groups of Sprague,Dawley rats were anaesthetized with isoflurane (ISO) (1.7% end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals were bled 15 mL kg,1 b.w. from the femoral vein over 10 min, followed by an observation period of 30 min. Ten minutes before haemorrhage each group of animals was pre-treated with intravenous injection/infusion of either: isotonic saline (Group B; CON; n=7), vasopressin V1 -receptor antagonist [d(CH2)5Tyr(Me)AVP; 10 ,g kg,1] (Group C; AVP-a; n=7), the non-selective angiotensin II receptor antagonist saralasin (10 ,g kg,1 min,1) (Group D; SAR; n=7) or hexamethonium (10 mg kg,1) (Group E; HEX; n=7). A separate group of conscious animals were pre-treated with isotonic NaCl and subjected to the same haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate (HR) and blood gases were observed during the experiments. Only pre-treatment with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only affected by HEX, which caused a reduction by 17%. The HR was significantly lower at the end of haemorrhage compared with pre-haemorrhage levels in all groups except that group treated with HEX. In that group the HR changed in the opposite direction. The ability to maintain MAP during haemorrhage, and the post-haemorrhage period, was significantly impaired in the groups treated with AVP-a, SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic nervous activity is of major importance for the maintenance of MAP during isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels contribute to a much smaller degree in this regard. General anaesthesia in combination with different degrees of neurohumoral blockade impairs the haemodynamic responses to blood loss, seen in conscious individuals. The impairment involves both the early and late phases during haemorrhage, as well as the post-bleeding recovery period. All three neurohumoral systems (autonomic nervous activity, angiotensin II and vasopressin) are of importance for regulating MAP during and after haemorrhage, although the autonomic nervous outflow appears to contribute to a larger extent. [source] A succession of anesthetic endpoints in the Drosophila brainDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2006Bruno van Swinderen Abstract General anesthetics abolish behavioral responsiveness in all animals, and in humans this is accompanied by loss of consciousness. Whether similar target mechanisms and behavioral endpoints exist across species remains controversial, although model organisms have been successfully used to study mechanisms of anesthesia. In Drosophila, a number of key mutants have been characterized as hypersensitive or resistant to general anesthetics by behavioral assays. In order to investigate general anesthesia in the Drosophila brain, local field potential (LFP) recordings were made during incremental exposures to isoflurane in wild-type and mutant flies. As in higher animals, general anesthesia in flies was found to involve a succession of distinct endpoints. At low doses, isoflurane uncoupled brain activity from ongoing movement, followed by a sudden attenuation in neural correlates of perception. Average LFP activity in the brain was more gradually attenuated with higher doses, followed by loss of movement behavior. Among mutants, a strong correspondence was found between behavioral and LFP sensitivities, thereby suggesting that LFP phenotypes are proximal to the anesthetic's mechanism of action. Finally, genetic and pharmacological analysis revealed that anesthetic sensitivities in the fly brain are, like other arousal states, influenced by dopaminergic activity. These results suggest that volatile anesthetics such as isoflurane may target the same processes that sustain wakefulness and attention in the brain. LFP correlates of general anesthesia in Drosophila provide a powerful new approach to uncovering the nature of these processes. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 1195,1211, 2006 [source] Maternal anesthesia via isoflurane or ether differentially affects pre-and postnatal behavior in rat offspringDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2007April E. Ronca Abstract Our understanding of prenatal behavior has been significantly advanced by techniques for direct observation and manipulation of unanesthetized, behaving rodent fetuses with intact umbilical connections to the mother. These techniques involve brief administration of an inhalant anesthesic, enabling spinal transection of the rat or mouse dam, after which procedures can continue with unanesthetized dams and fetuses. Because anesthetics administered to the mother can cross the placental barrier, it is possible that fetuses are anesthetized to varying degrees. We compared in perinatal rats the effects of prenatal maternal exposure to two inhalant anesthetics: ether and isoflurane. Fewer spontaneous fetal movements and first postpartum nipple attachments were observed following maternal exposure to ether as compared to isoflurane. Neonatal breathing frequencies and oxygenation did not account for group differences in nipple attachment. Our results provide evidence that the particular inhalant anesthetic employed in prenatal manipulation studies determines frequencies of perinatal behavior. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 675,684, 2007. [source] Enantioselective analysis of ketamine and its metabolites in equine plasma and urine by CE with multiple isomer sulfated ,-CDELECTROPHORESIS, Issue 15 2007Regula Theurillat Abstract CE with multiple isomer sulfated ,-CD as the chiral selector was assessed for the simultaneous analysis of the enantiomers of ketamine and metabolites in extracts of equine plasma and urine. Different lots of the commercial chiral selector provided significant changes in enantiomeric ketamine separability, a fact that can be related to the manufacturing variability. A mixture of two lots was found to provide high-resolution separations and interference-free detection of the enantiomers of ketamine, norketamine, dehydronorketamine, and an incompletely identified hydroxylated metabolite of norketamine in liquid/liquid extracts of the two body fluids. Ketamine, norketamine, and dehydronorketamine could be unambiguously identified via HPLC fractionation of urinary extracts and using LC-MS and LC-MS/MS with 1,mmu mass discrimination. The CE assay was used to characterize the stereoselectivity of the compounds' enantiomers in the samples of five ponies anesthetized with isoflurane in oxygen and treated with intravenous continuous infusion of racemic ketamine. The concentrations of the ketamine enantiomers in plasma are equal, whereas the urinary amount of R -ketamine is larger than that of S -ketamine. Plasma and urine contain higher S - than R -norketamine levels and the mean S -/R -enantiomer ratios of dehydronorketamine in plasma and urine are lower than unity and similar. [source] Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horsesEQUINE VETERINARY JOURNAL, Issue 1 2007S. M. THOMASY Summary Reasons for performing study: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. Objectives: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. Methods: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 ,g/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 × minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 ,g/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. Results: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. Conclusions and potential relevance: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses. [source] Binding of the volatile general anesthetics halothane and isoflurane to a mammalian ,-barrel proteinFEBS JOURNAL, Issue 2 2005Jonas S. Johansson A molecular understanding of volatile anesthetic mechanisms of action will require structural descriptions of anesthetic,protein complexes. Porcine odorant binding protein is a 157 residue member of the lipocalin family that features a large ,-barrel internal cavity (515 ± 30 Å3) lined predominantly by aromatic and aliphatic residues. Halothane binding to the ,-barrel cavity was determined using fluorescence quenching of Trp16, and a competitive binding assay with 1-aminoanthracene. In addition, the binding of halothane and isoflurane were characterized thermodynamically using isothermal titration calorimetry. Hydrogen exchange was used to evaluate the effects of bound halothane and isoflurane on global protein dynamics. Halothane bound to the cavity in the ,-barrel of porcine odorant binding protein with dissociation constants of 0.46 ± 0.10 mm and 0.43 ± 0.12 mm determined using fluorescence quenching and competitive binding with 1-aminoanthracene, respectively. Isothermal titration calorimetry revealed that halothane and isoflurane bound with Kd values of 80 ± 10 µm and 100 ± 10 µm, respectively. Halothane and isoflurane binding resulted in an overall stabilization of the folded conformation of the protein by ,0.9 ± 0.1 kcal·mol,1. In addition to indicating specific binding to the native protein conformation, such stabilization may represent a fundamental mechanism whereby anesthetics reversibly alter protein function. Because porcine odorant binding protein has been successfully analyzed by X-ray diffraction to 2.25 Å resolution [1], this represents an attractive system for atomic-level structural studies in the presence of bound anesthetic. Such studies will provide much needed insight into how volatile anesthetics interact with biological macromolecules. [source] Different behavioral effects of neurotoxic dorsal hippocampal lesions placed under either isoflurane or propofol anesthesiaHIPPOCAMPUS, Issue 3 2008Mark G. Baxter Abstract Anesthetic protocols for behavioral neuroscience experiments are evolving as new anesthetics are developed and surgical procedures are refined to improve animal welfare. We tested whether neurotoxic dorsal hippocampal lesions produced under two different anesthetic protocols would have different behavioral and/or histo-pathological effects. Rats were anesthetized with either propofol, an intravenous anesthetic, or isoflurane, a gaseous anesthetic, and multiple injections of an excitotoxin (N -methyl- D -aspartate) were stereotaxically placed in the dorsal hippocampus bilaterally. Intraoperative physiological parameters were similar in the two surgical groups, as were the volumes of the lesions, although the profile of postoperative impairment in a spatial learning task differed between the lesion groups depending on the anesthetic regimen used. These results show that the choice of anesthetic protocol is a critical variable in designing behavioral neuroscience experiments using neurosurgical procedures. This factor should be considered carefully in experimental design and in cross-study comparisons of lesion effects on behavior. © 2007 Wiley-Liss, Inc. [source] Constrained closed-loop control of depth of anaesthesia in the operating theatre during surgeryINTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Issue 5 2005M. Mahfouf Abstract The constrained version of generalized predictive control (GPC) which employs the quadratic programming (QP) approach is evaluated for on-line administration of an anaesthetic drug in the operating theatre during surgery. In the first instance, a patient simulator was developed using a physiological model of the patient and the necessary control software was validated via a series of extensive simulation experiments. Such a validated system was then transferred into the operating theatre for a series of clinical evaluation trials. The clinical trials, which were performed with little involvement of the design engineer, led to a good regulation of unconsciousness using fixed-parameters as well the adaptive version of the algorithm. Furthermore, the constrained algorithm displayed good robustness properties against disturbances such as high stimulus levels and allowed for safe and economically effective administration of the anaesthetic agent isoflurane. Copyright © 2005 John Wiley & Sons, Ltd. [source] A clinical prospective comparison of anesthetics sensitivity and hemodynamic effect among patients with or without obstructive jaundiceACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010L.-Q. YANG Background: To compare isoflurane anesthesia in patients with or without hyperbilirubinemia undergoing hepatobiliary surgery. Methods: Forty-two patients with obstructive jaundice and 40 control patients with normal liver function scheduled for hepatobiliary surgery under isoflurane anesthesia were studied. Anesthesia was induced with propofol (1.5,2 mg/kg) and remifentanil (2 ,g/kg). After tracheal intubation, anesthesia was titrated using isoflurane in oxygen-enriched air, adjusted to maintain a bispectral index (BIS) value of 46,54. Ephedrine, atropine and remifentanil were used to maintain hemodynamic parameters within 30% of the baseline. The mean arterial blood pressure (MAP), heart rate (HR), drug doses and the time taken to recover from anesthesia were recorded. Results: Demographic data, duration and BIS values were similar in both groups. Anesthesia induction and maintenance were associated with more hemodynamic instability in the patients with jaundice and they received more ephedrine and atropine and less remifentanil and isoflurane (51.1±24.2 vs. 84.6±20.3 mg/min; P for all <0.05) than control patients. Despite less anesthetic use, the time to recovery and extubation was significantly longer than that in control. Conclusion: Patients with obstructive jaundice have an increased sensitivity to isoflurane, more hypotension and bradycardia during anesthesia induction and maintenance and a prolonged recovery time compared with controls. [source] Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brainACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010R. D. SANDERS Background: Recent evidence has demonstrated the anti-apoptotic of dexmedetomidine in different brain injury models. Herein, we investigated whether dexmedetomidine could directly protect against cortical injury in vitro and in vivo. Methods: Apoptosis was induced by staurosporine or wortmannin treatment in cortical neuronal cultures in vitro or by 6 h of isoflurane (0.75%) administration to post-natal day 7 rat pups in vivo. Dexmedetomidine was then applied in escalating doses to assess the neuroprotective potential of this agent. Cell survival was quantified using an MTT assay in vitro and in vivo apoptosis was assessed using cleaved caspase-3 immunohistochemistry. Cortical Western blots were conducted for the cellular survival proteins Bcl-2 and phosphorylated extracellular signal-regulated protein kinase (pERK)1 and 2. Results: In vitro dexmedetomidine dose-dependently prevented both staurosporine- and wortmannin-induced injury in cortical neuronal cultures, indicating that dexmedetomidine can prevent apoptosis when applied directly. In vivo isoflurane induced cortical neuroapoptosis compared with air (327±80 vs. 34±9 caspase-3-positive neurons; P<0.05). Dexmedetomidine inhibited isoflurane-induced caspase-3 expression (P<0.05), although the protection achieved did not completely attenuate the isoflurane injury (P<0.05 vs. air). Isoflurane treatment decreased Bcl-2 and pERK protein expression relative to air, an effect reversed by dexmedetomidine treatment. Conclusions: Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed. [source] Xenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010M. HEIN Background: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate. Methods: The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were assessed in a porcine model (n=36) using the conductance catheter technique, and the expression of the type B natriuretic peptide (BNP) gene was measured. The animals underwent 90 min of right ventricular ischemia followed by 120 min of reperfusion. A barbiturate-anesthetized group was included as a control. Results: Cardiac output was compromised in unprotected animals during ischemia by 33±18% and during reperfusion by 53±17%. This was mainly due to impaired contractility in the left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase in stiffness and resulted in a higher preload. In contrast, xenon increased the right ventricular afterload, which was compensated by an increase in contractility. Its effects on diastolic function were less pronounced. Upregulation of BNP mRNA expression was impeded in the remote area of the LV by both isoflurane and xenon. Conclusions: Xenon and isoflurane demonstrated equipotent effects in preventing the hemodynamic compromise that is induced by right ventricular ischemia and reperfusion, although they acted through somewhat differential inotropic and vasodilatory effects. [source] Low-flow anaesthesia at a fixed flow rateACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009A. CHERIAN Aims and Objectives: This study attempts to assess the safety of low-flow anaesthesia (LFA) at fixed flow rates with particular reference to the incidence of a decline in FiO2 below safe levels of 0.3 and to determine whether LFA can be used safely in the absence of an FiO2 monitor. Methods: A total of 100 patients undergoing procedures under general anaesthesia at fresh gas flows of 300 ml/min of O2 and 300 ml/min of N2O were monitored while maintaining the dial setting of isoflurane at 1.5% for 2 h. The changes in gas composition were analysed and even a single recording of FiO2 of <0.3 was considered sufficient to render the technique unsafe in the absence of gas monitors. Results: The lowest recorded value of FiO2 was 31% (v/v%). There was no incidence of adverse events necessitating the conversion from low flows to conventional flows. Conclusions: We conclude that low flows of 300 ml/min of N2O and 300 ml/min of oxygen can be used safely for a period of 2 h without the use of monitors for gas analysis of oxygen and agent in adult patients weighing between 40 and 75 kgs. [source] Ketamine attenuates post-operative cognitive dysfunction after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009J. A. HUDETZ Background: Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect. Methods: Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day. Results: Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z -score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z -scores (P<0.001, Mann,Whitney U -test). Pre-operative CRP concentrations were similar (P<0.33, Mann,Whitney U -test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann,Whitney U -test) lower in the ketamine-treated than in the placebo-treated group. Conclusions: Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug. [source] Isoflurane attenuates pulmonary interleukin-1, and systemic tumor necrosis factor-, following mechanical ventilation in healthy miceACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009M. VANEKER Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. Methods: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH2O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. Results: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1, was found compared with non-ventilated control mice. Plasma: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-, was found compared with non-ventilated control mice. Conclusions: The present study is the first to show that isoflurane attenuates the pulmonary IL-1, and systemic TNF-, response following MV in healthy mice. [source] Isoflurane enhances spontaneous Ca2+ oscillations in developing rat hippocampal neurons in vitroACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009Q. XIANG Background: During the nervous system development, spontaneous synchronized Ca2+ oscillations are thought to possess integrative properties because their amplitude and frequency can influence the patterning of neuronal connection, neuronal differentiation, axon outgrowth, and long-distance wiring. Accumulating studies have confirmed that some drugs such as volatile anesthetic isoflurane produced histopathologic changes in the central nervous system in juvenile animal models. Because the hippocampus plays an important role in learning and memory, the present work was designed to characterize the Ca2+ oscillations regulated by volatile anesthetic isoflurane in primary cultures of developing hippocampal neurons (5-day-cultured). Methods: Primary cultures of rat hippocampal neurons (5-day-cultured) were loaded with the Ca2+ indicator Fluo-4AM (4 ,M) and were studied with a confocal laser microscope. Results: Approximately 22% of 5-day-cultured hippocampal neurons exhibited typical Ca2+ oscillations. These oscillations were dose-dependently enhanced by isoflurane (EC50 0.5 MAC, minimum alveolar concentration) and this effect could be reverted by bicuculline (50 ,M), a specific ,-aminobutyric acid (GABAA) receptor antagonist. Conclusion: Unlike its depressant effect on the Ca2+ oscillations in adult neurons in previous researches, isoflurane dose-dependently enhanced calcium oscillations in developing hippocampal neurons by activating GABAA receptors, a major excitatory receptor in synergy with N -methyl- d -aspartate receptors at the early stages of development. It may be involved in the mechanism of an isoflurane-induced neurotoxic effect in the developing rodent brain. [source] Isoflurane exerts a short-term but not a long-term preconditioning effect in neonatal rats exposed to a hypoxic-ischaemic neuronal injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009N. SASAOKA Background: Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury. Methods: Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI. Results: Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI. Conclusions: Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection. [source] | ||||||||||||||||||||||||||||||||||