Background

There is concern that maternal anesthesia during pregnancy impairs brain development of the human fetus. Xenon is neuroprotective in pre-clinical models of anesthesia-induced neurotoxicity in neonates. It is not known if xenon also protects the developing fetal brain when administered in addition to maternal sevoflurane-anesthesia during pregnancy.

Objective

To investigate the effects of sevoflurane and xenon on neurobehaviour and neurodevelopment of the offspring in a pregnant rabbit model.

Methods

Pregnant rabbits on post-conception day 28 (term = 31d) underwent two hours of general anesthesia with 1 minimum alveolar concentration (MAC) of sevoflurane in 30% oxygen (n = 17) or 1 MAC sevoflurane plus 50-60 % xenon in 30% oxygen (n = 10) during a standardized laparotomy while receiving physiological monitoring. A sham-group (n = 11) underwent monitoring alone for two hours. At term, the rabbits were delivered by caesarean section. On the first postnatal day, neonatal rabbits underwent neurobehavioral assessment using a validated test battery. Following euthanasia, the brains were harvested for neurohistological analysis. A mixed effects-model was used for statistical analysis.

Results

Maternal cardiopulmonary parameters during anesthesia were within the reference range. Fetal survival rates were significantly higher in the sham-group as compared to the sevoflurane-group and the fetal brain/body weight ratio was significantly lower in the sevoflurane-group as compared with the sham- and xenon-group. Pups antenatally exposed to anesthesia had significantly lower motor and sensory neurobehavioral scores when compared to the sham-group (mean ± SD; sevo: 22.70 ± 3.50 vs. sevo+xenon: 22.74 ± 3.15 vs. sham: 24.37 ± 1.59; overall p = 0.003; sevo: 14.98 ± 3.00 vs. sevo+xenon: 14.80 ± 2.83 vs. sham: 16.43 ± 2.63; overall p = 0.006; respectively). Neuron density, neuronal proliferation and synaptic density were reduced in multiple brain regions of the exposed neonates. The co-administration of xenon had no measurable neuroprotective effects in this model.

Conclusions

In rabbits, sevoflurane anesthesia for a standardized laparotomy during pregnancy resulted in impaired neonatal neurobehavior and a decreased neuron count in several regions of the neonatal rabbit brain. Co-administration of xenon did not prevent this effect.

中文翻译：

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氙气对母体七氟醚麻醉和剖腹手术后胎儿神经发育的影响

背景

人们担心怀孕期间的母体麻醉会损害人类胎儿的大脑发育。氙在新生儿麻醉诱导的神经毒性临床前模型中具有神经保护作用。目前尚不清楚在妊娠期间除母体七氟醚麻醉外，氙气是否也能保护发育中的胎儿大脑。

客观的

研究七氟醚和氙对妊娠兔模型后代神经行为和神经发育的影响。

方法

怀孕后第 28 天（足月 = 31 天）的怀孕兔接受了 2 小时的全身麻醉，其中 1 个最低肺泡浓度 (MAC) 的七氟醚在 30% 氧气中 ( n  = 17) 或 1 个 MAC 七氟醚加 50-60% 氙气在 30% 中 接受生理监测的标准化剖腹手术期间的氧气百分比（n = 10）。一个假组（n  = 11）单独进行了两个小时的监测。在足月，兔子通过剖腹产分娩。在出生后的第一天，使用经过验证的测试电池对新生兔进行神经行为评估。安乐死后，收集大脑用于神经组织学分析。使用混合效应模型进行统计分析。

结果

麻醉期间产妇心肺参数均在参考范围内。与七氟醚组相比，假手术组的胎儿存活率显着更高，与假手术组和氙气组相比，七氟醚组的胎儿脑/体重比显着降低。与假手术组相比，产前暴露于麻醉的幼崽的运动和感觉神经行为评分显着降低（平均值±标准差；sevo：22.70 ± 3.50 vs. sevo + xenon：22.74 ± 3.15 vs. sham：24.37 ± 1.59；总体p  = 0.003；sevo：14.98 ± 3.00 vs. sevo+xenon：14.80 ± 2.83 vs. sham：16.43 ± 2.63；总体p = 0.006; 分别）。暴露新生儿的多个脑区神经元密度、神经元增殖和突触密度降低。在该模型中，氙的共同给药没有可测量的神经保护作用。

结论

在兔子中，在怀孕期间进行标准化剖腹手术的七氟醚麻醉导致新生儿神经行为受损，并且在新生儿兔大脑的几个区域中神经元数量减少。氙气的共同给药并没有阻止这种效果。