Long-term effects of combined brilliant blue G and xenon light induced retinal toxicity following macular hole repair surgery.

BACKGROUND: The purpose of this study was to look at the long-term effects of retinal phototoxicity after macular hole repair surgery using xenon endolight illumination and Brilliant blue G (BBG) dye. CASE PRESENTATION: An elderly man in his late seventies underwent para plana vitrectomy with BBG dye to repair an idiopathic full-thickness macular hole (MH) in his right eye. Prior to macular hole surgery, his visual acuity in the right eye was 6/60, N24 at the time of presentation. The MH closed with type 1 closure immediately after surgery, but there was extensive damage to the outer retinal layers and retinal pigment epithelium (RPE) at the macula, resulting in a reduction in visual acuity to 2/60. We presumed that the combination of BBG and xenon light, is the probable reason of retinotoxicity in the current patient. There was a progressive increase in the area of retinal and RPE layer damage and choroidal thinning over a 4-year period. CONCLUSION: Due to combined BBG-induced dye and endoilluminator toxicity, a rare case of continuously progressing RPE layer damage with choroidal thinning over a long follow-up interval was described. Such long-term effects of BBG and endolight induced retinotoxicity have not been reported in the literature, to the best of our knowledge.

Xenon neurotoxicity in rat hippocampal slice cultures is similar to isoflurane and sevoflurane.

BACKGROUND: Anesthetic neurotoxicity in the developing brain of rodents and primates has raised concern. Xenon may be a nonneurotoxic alternative to halogenated anesthetics, but its toxicity has only been studied at low concentrations, where neuroprotective effects predominate in animal models. An equipotent comparison of xenon and halogenated anesthetics with respect to neurotoxicity in developing neurons has not been made. METHODS: Organotypic hippocampal cultures from 7-day-old rats were exposed to 0.75, 1, and 2 minimum alveolar concentrations (MAC) partial pressures (60% xenon at 1.2, 2.67, and 3.67 atm; isoflurane at 1.4, 1.9, and 3.8%; and sevoflurane at 3.4 and 6.8%) for 6 h, at atmospheric pressure or in a pressure chamber. Cell death was assessed 24 h later with fluorojade and fluorescent dye exclusion techniques. RESULTS: Xenon caused death of hippocampal neurons in CA1, CA3, and dentate regions after 1 and 2 MAC exposures, but not at 0.75 MAC. At 1 MAC, xenon increased cell death 40% above baseline (P < 0.01; ANOVA with Dunnett test). Both isoflurane and sevoflurane increased neuron death at 1 but not 2 MAC. At 1 MAC, the increase in cell death compared with controls was 63% with isoflurane and 90% with sevoflurane (both P < 0.001). Pretreatment of cultures with isoflurane (0.75 MAC) reduced neuron death after 1 MAC xenon, isoflurane, and sevoflurane. CONCLUSION: Xenon causes neuronal cell death in an in vitro model of the developing rodent brain at 1 MAC, as does isoflurane and sevoflurane at similarly potent concentrations. Preconditioning with a subtoxic dose of isoflurane eliminates this toxicity.

Prevention of neurotoxicity in hypoxic cortical neurons by the noble gas xenon.

Hypoxia-induced neuronal damage and glutamate release were investigated in a N(2)- or in xenon-atmosphere for embryonic rat cortical neurons; cellular damage and glutamate over-release were observed in N(2)-treated cells whereas xenon protected the cells from the hypoxic insult. The protective effect of xenon was strongly reduced by pre-incubating neurons with the calcium-chelator BAPTA-AM indicating a role for calcium in this process. The results demonstrate (a) the neuroprotective properties of xenon, suggest (b) a relationship between the prevention of neurotransmitter release in a hypoxic situation and neuroprotection and present (c) evidence that such neuroprotection may be based on yet other xenon-dependent mechanisms.

[Influence of xenon on reproductive function]. / Vliianie ksenona na reproduktivnuiu funktsiiu.

Wistar rats were used in the study. 15 male rats were exposed to Xe:O2(80:20) mixture for 2 hours twice a week during 10 weeks, and 60 female rats were affected similarly for 2 weeks. The three groups have been formed: 1st group consists of 15 exposed males joined by 30 control female rats, 2nd group includes 30 exposed female rats and 15 control male rats, 15 control male rats and 30 control female rats were in the 3rd group. Xe:O2(80:20) inhalation affect neither fertility and pregnancy indices, which reached 90%, nor body mass gain during pregnancy, nor pre- and postimplantation embryonal death, neonatal body mass and development. Xenon does not impair fine mechanisms of reproductive function, being most safe gas anesthetic with nice prospects for applying in obstetrical clinics.

[Investigation of the teratogenic and embryotoxic action of xenon]. / Issledovaniia teratogennogo i émbriotoksicheskogo deistviia ksenona.

30 Wistar rats inhaled a Xe (80%):O2(20%) mixture for 2 hours twice a week on the 1st to 19th days of pregnancy. On the 20th day of pregnancy 70% rats were exposed to euthanasia, the rest of animals were left for labors to study the postnatal course in the progeny. Inhaling the Xe (80%):O2(20%) mixture did not affect either the changes in body mass of pregnant rats, indices of postimplantating loss of embryos and pregnancy duration or the number of live newborns, their body mass and sizes. Xenon caused neither inhibition of osteal system development nor any malformations. The results of study permit one to look optimistically at the prospects for using Xenon in obstetrical anesthesiology.

Effects of repeated exposures to xenon on rat adrenal cortex ultrastructure.

Xenon has many properties of the ideal anaesthetic and it has been proposed to replace classic volatile anaesthetics. Although some studies demonstrated that xenon does not induce gross morphological changes in major organs, little is known on its possible ultrastructural effects. The present study investigates the subcellular effects of repeated exposures to 70% xenon on rat adrenal cortex in comparison with N2O. Animals were divided into four groups: xenon-exposed, N2O-exposed, sham-exposed and controls. Exposed rats were placed into a sealed cage to breathe the respective gas mixture for 2.5 h/day for a week. Specimens of adrenal cortex for electron microscopy and blood samples for determination of corticosterone plasma levels were taken at the end of the last exposure or one week after the last exposure (recovery). Adrenal cortex from N2O- and sham-exposed rats mainly showed dilation of endoplasmic reticulum, whereas xenon-exposed rats also exhibited several cells with lipid droplets appearing subdivided into smaller droplets, irregular in shape and size. In all experimental groups, corticosterone plasma levels increased in comparison to controls. Both ultrastructural and hormonal changes were not detected anymore after one week from the last exposure. These findings indicate that xenon is able to induce subcellular changes in rat adrenal cortex, mainly at the level of lipid structures. The transient changes induced by xenon suggest that this gas can be regarded as a safer anaesthetic.

Neuroprotective and neurotoxic properties of the 'inert' gas, xenon.

BACKGROUND: Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors have been shown not only to have neuroprotective effects but also to exhibit neurotoxic properties. In this study, we used c-Fos, a protein product of an immediate early gene, as a marker of neuronal injury to compare the neuroprotective effects of xenon and the neurotoxic properties of xenon, nitrous oxide, and ketamine, three anaesthetics with NMDA receptor antagonist properties. METHODS: We used an in vivo rat model of brain injury in which N-methyl-DL-aspartic acid (NMA) is injected subcutaneously (s.c.) and c-Fos expression in the arcuate nucleus is used as a measure of injury. To examine the neurotoxic potential of each of the three anaesthetics with NMDA receptor antagonist properties, c-Fos expression in the posterior cingulate and retrosplenial (PC/RS) cortices was measured. RESULTS: Xenon dose-dependently suppressed NMA-induced c-Fos expression in the arcuate nucleus with an IC(50) of 47 (2)% atm. At the highest concentration tested (75% atm) NMA-induced neuronal injury was decreased by as much as that observed with the prototypical NMDA antagonist MK801 (0.5 mg kg(-1) s.c.). Both nitrous oxide and ketamine dose-dependently increased c-Fos expression in PC/RS cortices; in contrast, xenon produced no significant effect. If the dopamine receptor antagonist haloperidol was given before either nitrous oxide or ketamine, their neurotoxic effects were eliminated. CONCLUSIONS: Uniquely amongst anaesthetics with known NMDA receptor antagonist action, xenon exhibits neuroprotective properties without co-existing neurotoxicity. The reason why ketamine and nitrous oxide, but not xenon, produce neurotoxicity may involve their actions on dopaminergic pathways.

[Study of immunodepressive and allergic effects of xenon]. / Issledovaniia immunodepressornykh i allergiziruiuscchikh svoistv ksenona.

Experimental studies on mice showed that after four 30-min and 60-min inhalations of Xe:O2 (80:20) during 2 weeks, weight indexes of the lymphoid organs (spleen and thymus) increased, phagocytic activity did not change, and primary immune response was moderately stimulated. This indicates that xenon exerted no immunotoxic effects and can be used in patients with diseases associated with primary immunodeficiency. Study of allergic effects on albino guinea pigs showed that on days 14 and 21 of sensitization xenon in the resolving dose possessed no anaphylactogenic activity, caused no specific lysis of leukocytes, and did not modulate the counts of basophils and eosinophils. Xenon did not induce allergic reactions and is not a potential allergen, which is important in patients with panallergy.

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.

[Clinical and experimental study of xenon anesthesia]. / Kliniko-éksperimental'nye issledovaniia anestezii ksenonom.

Narcotic effect of inert gas xenon (Xe) was discovered more than 50 years ago. The main causes limiting its clinical application are high price, low availability (in nature the gas is present in scarce amounts), and absence of preclinical trials sufficient for norm-setting documents and further solutions allowing clinical trials of Xe. Results of original and basic clinical and experimental studies of xenon anesthesia are presented. The studies were carried out by a group of authors in accordance with the requirements and norm-setting documents of Pharmacological Committee of Ministry of Health of the Russian Federation, needed for permitting Xe for medical application as a new narcotic agent.

Respiratory depression in goats by stable xenon: implications for CT studies.

The pharmacology of stable xenon is of practical importance to users of the xenon CT-regional cerebral blood flow method. In a study in goats we have demonstrated that xenon has a characteristic respiratory depressant effect, unlike effects of comparable anesthetic concentrations of nitrous oxide and halothane.

Anesthetics as teratogens: nitrous oxide is fetotoxic, xenon is not.

Exposure of pregnant rats to the anesthetic nitrous oxide on the ninth day of gestation causes fetal resorption, skeletal anomalies, and macroscopic lesions including encephalocele, anophthalmia, microphthalmia, and gastroschisis. The inert gas xenon, which has anesthetic properties similar to those of nitrous oxide, does not cause teratogenic effects under the same experimental conditions.