Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass: phase I study

BACKGROUND: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system. METHODS: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery. RESULTS: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100beta levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout. CONCLUSIONS: Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.     

Effects of xenon on in vitro and in vivo models of neuronal injury

BACKGROUND: Xenon, the "inert" gaseous anesthetic, is an antagonist at the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Because of the pivotal role that NMDA receptors play in neuronal injury, the authors investigated the efficacy of xenon as a neuroprotectant in both in vitro and in vivo paradigms. METHODS: In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, glutamate, or oxygen deprivation and assessed by the release of lactate dehydrogenase into the culture medium. Increasing concentrations of either xenon or nitrogen (10-75% of an atmosphere) were coadministered and maintained until injury was assessed. In separate in vivo experiments, rats were administered N-methyl-dl-aspartate and killed 3 h later. Injury was quantified by histologic assessment of neuronal degeneration in the arcuate nucleus of the hypothalamus. RESULTS: Xenon exerted a concentration-dependent protection against neuronal injury provoked by NMDA (IC(50) = 19 +/- 6% atm), glutamate (IC(50) = 28 +/- 8% atm), and oxygen deprivation (IC(50) = 10 +/- 4% atm). Xenon (60% atm) reduced lactate dehydrogenase release to baseline concentrations with oxygen deprivation, whereas xenon (75% atm) reduced lactate dehydrogenase release by 80% with either NMDA- or glutamate-induced injury. In an in vivo brain injury model in rats, xenon exerted a concentration-dependent protective effect (IC(50) = 78 +/- 8% atm) and reduced the injury by 45% at the highest xenon concentration tested (75% atm). CONCLUSIONS: Xenon, when coadministered with the injurious agent, exerts a concentration-dependent neuroprotective effect at concentrations below which anesthesia is produced in rodents. Unlike either nitrous oxide or ketamine (other anesthetics with NMDA antagonist properties), xenon is devoid of both neurotoxicity and clinically significant adverse hemodynamic properties. Studies are proposed to determine whether xenon can be used as a neuroprotectant in certain clinical settings.     

Xenon modulates neutrophil adhesion molecule expression in vitro

BACKGROUND AND OBJECTIVE: Xenon reduces the infarct size after regional ischaemia in the rabbit heart in vivo, but the underlying mechanisms are unknown. Since adhesion molecules on neutrophils are closely involved in the pathophysiology of ischaemia/reperfusion injury and modulation of neutrophil function, we investigated the effect of xenon on neutrophil adhesion molecule expression in vitro. METHODS: Freshly isolated neutrophils were incubated with 30% or 60% xenon for 60 min. In unstimulated and after stimulation with either N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate neutrophil surface expression of PSGL-1, L-selectin, CD11a and CD11b were measured by flow cytometry. RESULTS: At both concentrations, xenon reduced the surface expression of PSGL-1 by 10% (P < 0.05), and of L-selectin by 15% (P < 0.05) in the 60% xenon group. Furthermore, N-formyl-methionyl-leucyl-phenylalanine activated neutrophils showed an increased removal of L-selectin from the neutrophil surface following incubation with xenon (30% compared to controls, P < 0.05). Neutrophil beta2-integrin expression was not altered by xenon. CONCLUSIONS: Xenon increases the removal of the selectins PSGL-1 and L-selectin from the neutrophil surface in vitro. Since both selectins are involved in the initial contact between neutrophils and endothelial cells, xenon may affect neutrophil adhesion to endothelium during ischaemia/reperfusion injury. However, because the beta2-integrin expression was unaffected by xenon, further investigations are required to clarify whether xenon may modulate neutrophil transmigration through endothelial cells in vivo.     

Feasibility and Safety of Delivering Xenon to Patients Undergoing Coronary Artery Bypass Graft Surgery While on Cardiopulmonary Bypass: Phase I Study

Background: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system.

Methods: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery.

Results: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100[beta] levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout.     

Xenon administration during early reperfusion reduces infarct size after regional ischemia in the rabbit heart in vivo

The noble gas xenon can be used as an anesthetic gas with many of the properties of the ideal anesthetic. Other volatile anesthetics protect myocardial tissue against reperfusion injury. We investigated the effects of xenon on reperfusion injury after regional myocardial ischemia in the rabbit. Chloralose-anesthetized rabbits were instrumented for measurement of aortic pressure, left ventricular pressure, and cardiac output. Twenty-eight rabbits were subjected to 30 min of occlusion of a major coronary artery followed by 120 min of reperfusion. During the first 15 min of reperfusion, 14 rabbits inhaled 70% xenon/30% oxygen (Xenon), and 14 rabbits inhaled air containing 30% oxygen (Control). Infarct size was determined at the end of the reperfusion period by using triphenyltetrazolium chloride staining. Xenon reduced infarct size from 51%+/-3% of the area at risk in controls to 39%+/-5% (P<0.05). Infarct size in relation to the area at risk size was smaller in the xenon-treated animals, indicated by a reduced slope of the regression line relating infarct size to the area at risk size (Control: 0.70+/-0.08, r = 0.93; Xenon: 0.19+/-0.09, r = 0.49, P<0.001). In conclusion, inhaled xenon during early reperfusion reduced infarct size after regional ischemia in the rabbit heart in vivo.     

Inert gases as the future inhalational anaesthetics?

Of all the inert gases, only xenon has considerable anaesthetic properties under normobaric conditions. Its very low blood/gas partition coefficient makes induction of and emergence from anaesthesia more rapid compared with other inhalational anaesthetics. In experimental and clinical studies the safety and efficiency of xenon as an anaesthetic has been demonstrated. Xenon causes several physiological changes, which mediate protection of the brain or myocardium. The use of xenon might therefore be beneficial in certain clinical situations, as in patients at high risk for neurological or cardiac damage.     

The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits

Xenon may increase cerebral blood flow and intracranial pressure (ICP). To evaluate the effects of xenon on brain circulation, we measured pial vessel diameter changes, CO(2) reactivity, and ICP during xenon inhalation in rabbits. Minimum alveolar anesthetic concentration (MAC) for xenon was established in rabbits (n = 6). By using a cranial window model, pial vessel diameters were measured at 30% and 60% xenon inhalation and in time control groups (n = 15). ICP, mean arterial blood pressure, and heart rate were recorded during 30% and 60% xenon inhalation (n = 5). Pial vessel diameters were measured during hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14). MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and 18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of arterioles was more prominent than that of venules. ICP, mean arterial blood pressure, and heart rate did not change during xenon inhalation. No difference in CO(2) reactivity was observed between Xenon and Control groups (P = 0.79). Sixty percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small. Xenon did not increase ICP and preserved CO(2) reactivity of the brain vessels. IMPLICATIONS: Xenon might increase cerebral blood flow; however, 0.7 minimum alveolar anesthetic concentration xenon preserved both low intracranial pressure and CO(2) reactivity of the cerebral vessels in the normal rabbit.     

Effects of Xenon on In Vitro and In Vivo Models of Neuronal Injury

Background: Xenon, the "inert" gaseous anesthetic, is an antagonist at the N-methyl-d-aspartate (NMDA)-type glutamate receptor. Because of the pivotal role that NMDA receptors play in neuronal injury, the authors investigated the efficacy of xenon as a neuroprotectant in both in vitro and in vivo paradigms.

Methods: In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, glutamate, or oxygen deprivation and assessed by the release of lactate dehydrogenase into the culture medium. Increasing concentrations of either xenon or nitrogen (10-75% of an atmosphere) were coadministered and maintained until injury was assessed. In separate in vivo experiments, rats were administered N-methyl-dl-aspartate and killed 3 h later. Injury was quantified by histologic assessment of neuronal degeneration in the arcuate nucleus of the hypothalamus.

Results: Xenon exerted a concentration-dependent protection against neuronal injury provoked by NMDA (IC50 = 19 +/- 6% atm), glutamate (IC50 = 28 +/- 8% atm), and oxygen deprivation (IC50 = 10 +/- 4% atm). Xenon (60% atm) reduced lactate dehydrogenase release to baseline concentrations with oxygen deprivation, whereas xenon (75% atm) reduced lactate dehydrogenase release by 80% with either NMDA- or glutamate-induced injury. In an in vivo brain injury model in rats, xenon exerted a concentration-dependent protective effect (IC50 = 78 +/- 8% atm) and reduced the injury by 45% at the highest xenon concentration tested (75% atm).     

Effect of caffeic acid phenethyl ester on survival of axial pattern flaps in rats with ischaemia-reperfusion injuries.

Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.     

Anaesthesia and the 'inert' gases with special reference to xenon.

Xenon has many of the properties of the ideal anaesthetic agent and has been proposed as a suitable replacement for nitrous oxide in routine clinical anaesthesia. Xenon, krypton and argon are chemically inert under most circumstances, yet all have anaesthetic properties. Xenon is of particular interest because it is the only 'inert' gas which is an anaesthetic under normobaric conditions. Because of this property, xenon has an important place in the history of the development of theories of anaesthetic action and of concepts such as MAC. Cost is likely to be a major impediment to the regular use of xenon.     

Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon

BACKGROUND: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon. METHODS: The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. RESULTS: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component. CONCLUSIONS: For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.     

Xenon inhibits but N(2)O enhances ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices

Both nitrous oxide (N(2)O) and xenon are N:-methyl-D-aspartate receptor antagonists that have psychotomimetic effects and cause neuronal injuries in the posterior cingulate and retrosplenial cortices. We investigated the effect of xenon, xenon with ketamine, N(2)O, and N(2)O with ketamine on c-Fos expression in the rat posterior cingulate and retrosplenial cortices, a marker of psychotomimetic effects. Brain sections were prepared, and c-Fos expression was detected with immunohistochemical methods. A loss of microtubule-associated protein 2, a marker of neuronal injury, was also investigated. The number of Fos-like immunoreactivity positive cells by ketamine IV at a dose of 5 mg/kg under 70% N(2)O (128 +/- 12 cells per 0.5 mm(2)) was significantly more than those under 30% (15 +/- 2 cells per 0.5 mm(2)) and 70% xenon (2 +/- 1 cells per 0.5 mm(2)). Despite differences in c-fos immunoreactivity, there was no loss of microtubule-associated protein 2 immunoreactivity in any group examined. Xenon may suppress the adverse neuronal effects of ketamine, and combined use of xenon and ketamine seems to be safe in respect to neuronal adverse effects.     

Neurologic and cognitive outcomes associated with the clinical use of xenon: a systematic review and meta-analysis of randomized-controlled trials

Background

Xenon has been shown to have positive neurologic effects in various pre-clinical models. This study systematically reviewed the randomized-controlled trials (RCTs) investigating neurologic and cognitive outcomes associated with the clinical use of xenon.

Methods

We searched PubMed, CENTRAL, EMBASE, CINAHL, elibrary.ru (for Russian studies), Google Scholar (for Russian studies), and Wanfang (for Chinese studies) for appropriate RCTs comparing neurologic or cognitive outcomes after clinical use of xenon with control treatment or with other anesthetic agents.

Results

Seventeen RCTs met the inclusion criteria. Two studies investigated the effects of xenon plus therapeutic hypothermia to treat neonatal asphyxia or out-of-hospital cardiac arrest. Compared with therapeutic hypothermia alone, xenon and therapeutic hypothermia reduced cerebral white matter abnormalities after cardiac arrest but had no effect on neurocognitive outcome and mortality. Xenon had no added value when used to treat neonatal asphyxia. Thirteen RCTs compared neurocognitive effects of xenon with other anesthetic agents in surgical patients. While xenon may be associated with improved short-term (< three hours) cognitive outcome, no medium-term (six hours to three months) advantage was observed, and longer-term data are lacking. No differences in biochemical (S-100β, neuron-specific enolase) and neuropsychologic (attentional performance) outcomes were found with xenon compared with other anesthetic drugs. Finally, two studies suggest that brief, intermittent administration of sub-anesthetic doses of xenon to patients during the acute phase of substance withdrawal may improve neurocognitive outcomes.

Conclusions

Despite promising pre-clinical results, the evidence for positive clinical neurologic and cognitive outcomes associated with xenon administration is modest. Nevertheless, there is some evidence to suggest that xenon may be associated with better neurologic outcomes compared with the standard of care therapy in certain specific clinical situations. More clinical trials are needed to determine any potential benefit linked to xenon administration.

     

Expansion of Gas Bubbles by Nitrous Oxide and Xenon

Background: Nitrous oxide is well known to expand gas bubbles trapped in enclosed spaces and is contraindicated in situations where this may occur. Xenon, an anesthetic gas with similar physical properties to nitrous oxide, is also likely to expand gas bubbles, and it has been predicted that microbubbles in the circulation may expand dramatically when exposed to xenon. Because of the possibility that xenon will be used during cardiopulmonary bypass surgery, a procedure that is likely to introduce microbubbles into the circulation, the authors reinvestigated the extent to which xenon expands gas bubbles in aqueous solution.

Methods: Gas bubbles of either air or oxygen were formed in an aqueous solution, and their size was monitored using optical microscopy when they were exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen mixture.

Results: Both nitrous oxide and xenon rapidly expanded air bubbles, although nitrous oxide caused a much larger expansion. The observed expansion was not greatly dependent on the initial size of the bubble but was significantly greater at lower temperatures. Under conditions relevant to cardiopulmonary bypass surgery (50% xenon-50% oxygen, 30[degrees]C), the increase in diameter was modest (9.7 +/- 0.8%).     

Expansion of gas bubbles by nitrous oxide and xenon

BACKGROUND: Nitrous oxide is well known to expand gas bubbles trapped in enclosed spaces and is contraindicated in situations where this may occur. Xenon, an anesthetic gas with similar physical properties to nitrous oxide, is also likely to expand gas bubbles, and it has been predicted that microbubbles in the circulation may expand dramatically when exposed to xenon. Because of the possibility that xenon will be used during cardiopulmonary bypass surgery, a procedure that is likely to introduce microbubbles into the circulation, the authors reinvestigated the extent to which xenon expands gas bubbles in aqueous solution. METHODS: Gas bubbles of either air or oxygen were formed in an aqueous solution, and their size was monitored using optical microscopy when they were exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen mixture. RESULTS: Both nitrous oxide and xenon rapidly expanded air bubbles, although nitrous oxide caused a much larger expansion. The observed expansion was not greatly dependent on the initial size of the bubble but was significantly greater at lower temperatures. Under conditions relevant to cardiopulmonary bypass surgery (50% xenon-50% oxygen, 30 degrees C), the increase in diameter was modest (9.7 +/- 0.8%). CONCLUSIONS: Although xenon does expand small air and oxygen bubbles, the extent to which this occurs under clinically relevant conditions of concentration and temperature is modest.     

Xenon and isoflurane improved biventricular function during right ventricular ischemia and reperfusion

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.     

Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofol

Background: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits. Methods: Thirty‐two male New Zealand white rabbits were randomly assigned to one of three groups. In the xenon and propofol group, 70% of xenon and 0.8 mg/kg/min of propofol were administered 30 min before an aortic occlusion and maintained until the end of the procedure. The aortic occlusion was performed for 15 min. In the sham group, the aorta was not occluded. After an assessment of the hind limb motor function using the Tarlov score (0=paraplegia, 4=normal) at 48 h after reperfusion, gray and white matter injuries were evaluated based on the number of normal neurons in the anterior spinal cord and the percentage areas of vacuolation in the white matter, respectively. Results: In the xenon and propofol groups, the Tarlov score and the number of normal neurons were significantly lower than those in the sham group, whereas the percentage areas of vacuolation were similar among the three groups. There were no significant differences in Tarlov scores and the number of normal neurons between the xenon and the propofol groups. Conclusion: The results indicated that 70% of xenon has no additional neuroprotective effects on ischemic spinal cord injury in rabbits compared with propofol.     

Xenon acts by inhibition of non-N-methyl-D-aspartate receptor-mediated glutamatergic neurotransmission in Caenorhabditis elegans

BACKGROUND: Electrophysiologic experiments in rodents have found that nitrous oxide and xenon inhibit N-methyl-D-aspartate (NMDA)-type glutamate receptors. These findings led to the hypothesis that xenon and nitrous oxide along with ketamine form a class of anesthetics with the identical mechanism, NMDA receptor antagonism. Here, the authors ask in Caenorhabditis elegans whether xenon, like nitrous oxide, acts by a NMDA receptor-mediated mechanism. METHODS: Xenon:oxygen mixtures were delivered into sealed chambers until the desired concentration was achieved. The effects of xenon on various behaviors were measured on wild-type and mutant C. elegans strains. RESULTS: With an EC50 of 15-20 vol% depending on behavioral endpoint, xenon altered C. elegans locomotion in a manner indistinguishable from that of mutants in glutamatergic transmission. Xenon reduced the frequency and duration of backward locomotion without altering its speed or other behaviors tested. Mutation of glr-1, encoding a non-NMDA glutamate receptor subunit, abolished the behavioral effects of xenon; however, mutation of nmr-1, which encodes the pore-forming subunit of an NMDA glutamate receptor previously shown to be required for nitrous oxide action, did not significantly alter xenon response. Transformation of the glr-1 mutant with the wild-type glr-1 gene partially restored xenon sensitivity, confirming that glr-1 was necessary for the full action of xenon. CONCLUSIONS: Xenon acts in C. elegans to alter locomotion through a mechanism requiring the non-NMDA glutamate receptor encoded by glr-1. Unlike for the action of nitrous oxide in C. elegans, the NMDA receptor encoded by nmr-1 is not essential for sensitivity to xenon.     

Xenon Does Not Trigger Malignant Hyperthermia in Susceptible Swine

Background: Xenon is a noble gas with anesthetic properties currently under investigation for use in humans. This study was performed to evaluate whether xenon may trigger malignant hyperthermia in susceptible swine.

Methods: Nine malignant hyperthermia-sensitive swine (Pietrain) were initially anesthetized with pentobarbital and then ventilated with 70% xenon in oxygen for 2 h. Heart rate, mean arterial pressure, cardiac output, body temperature, arterial and mixed-venous blood gases, and plasma catecholamine and lactate levels were measured every 10 min both during xenon-oxygen ventilation and after a 30-min xenon washout phase followed by subsequent administration of halothane (1% inspired) and succinylcholine (3 mg/kg intravenous). During the investigation, no malignant hyperthermia-specific therapy was instituted.

Results: Xenon exposure did not induce any changes in metabolic and hemodynamic parameters nor elevations of the plasma catecholamine levels indicative for an episode of malignant hyperthermia. By contrast, in all animals, within 20 min after the administration of halothane and succinylcholine, fulminant and fatal malignant hyperthermia episodes were initiated.     

氙气麻醉的临床药理新进展

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