Anesthetics as tEratogens: Nitrous Oxide Is Fetotoxic, Xenon Is Not

Lane, Geoffrey A.; Nahrwold, Michael L.; Tait, Alan R.; Taylor-Busch, M.; Cohen, Peter J.; Beaudoin, Adrien R.

doi:10.1126/science.7434002

Cited by 274 publications

(88 citation statements)

References 12 publications

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“…Therefore, for an intervention to be maximally effective, it may need to be used before, during, or immediately after birth. Xenon's preconditioning properties coupled to its powerful neuroprotective capabilities and absence of fetotoxicity (Lane et al, 1980;Fukura et al, 2000) might have clinical implications in terms of both the prevention as well as the treatment of neonatal asphyxia.…”

Section: Discussionmentioning

confidence: 99%

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Hossain

Pettet

et al. 2006

J Cereb Blood Flow Metab

166

111

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Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3 0 ,5 0 -monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.

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Section: Discussionmentioning

confidence: 99%

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Hossain

Pettet

et al. 2006

J Cereb Blood Flow Metab

166

111

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“…Xenon is also attractive in this role because of its lack of chemical reactivity and lack of clinical side effects (Dingley et al, 2001;Marx et al, 1997;Preckel et al, 2004;Rossaint et al, 2003), rapid reversibility, and lack of fetotoxicity (Burov et al, 2002;Lane et al, 1980). A radioisotope of Xe (Xe 133 ) has been used in neonates by injecting Xe 133 dissolved in 1 ml of water and counting the distribution of radioactivity as a measure of blood flow.…”

Section: Introductionmentioning

confidence: 99%

Cooling Combined with Immediate or Delayed Xenon Inhalation Provides Equivalent Long-Term Neuroprotection after Neonatal Hypoxia—Ischemia

Thoresen

Hobbs

Wood

et al. 2009

J Cereb Blood Flow Metab

151

117

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Hypothermia (HT) improves outcome after neonatal hypoxia-ischemia. Combination therapy may extend neuroprotection. The noble anesthetic gas xenon (Xe) has an excellent safety profile. We have shown earlier that 3 h of 50% Xe plus HT (321C) additively gives more protection (72%) than either alone (HT = 31.1%, Xe = 10.2%). Factors limiting clinical use include high-cost and specialist administration requirements. Thus, combinations of 1 h of 50% Xe were administered concurrently for either the first (1 h Immediate Xe) or last (1 h Delayed Xe) of 3 h of posthypoxic-ischemic HT as compared with 3 h of 50%Xe/HT to investigate how brief Xe exposure with a delay would affect efficacy. An established neonatal rat hypoxia-ischemia model was used. Serial functional neurologic testing into adulthood was performed, followed by neuropathological examination. Xenon with HT was more effective with longer Xe duration (3 h versus 1 h) (P = 0.015). However, 1 h Xe/3 h HT resulted in better neuroprotection than 3 h HT alone (P = 0.03), this significant effect was also present with 1 h Xe after a 2-h delay. One (immediate or with a delay) or 3 h Xe also significantly improved motor function (P = 0.024). Females had significantly better motor scores than males, but no sex-dependent difference in pathology results. The neuroprotection of short, delayed Xe treatment would allow transport to specialist facilities to receive Xe.

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“…3,4 Xenon was also suggested as a potential alternative to N 2 O because it is not teratogenic. 5 A recent randomized, controlled, multicentre study showed that anesthesia with xenon is safe and provides a more rapid recovery than isoflurane with N 2 O. 6 Although it is not surprising that the patients in the study by Lachmann and co-workers 1 receiving one minimum alveolar concentration (MAC) of xenon required less fentanyl than the patients receiving 0.7 MAC of N 2 O, the difference was far greater than expected from the difference in MAC.…”

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confidence: 76%