Developmental effects of neonatal isoflurane and sevoflurane exposure in rats.
Developmental effects of neonatal isoflurane and sevoflurane exposure in rats.
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DOI：
10.1097/aln.0b013e318291c04e
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发表时间：
2013-08
期刊：
影响因子：
8.8
通讯作者：
Martynyuk AE
中科院分区：
文献类型：
--
作者：
Seubert CN;Zhu W;Pavlinec C;Gravenstein N;Martynyuk AE
全麻药异氟醚和七氟醚通过不完全了解的机制导致新生动物模型的发育异常。尽管有许多共同的分子靶点，但异氟醚和七氟烷在作用上表现出很大的差异。我们试图确定这些差异是否也可以在神经发育影响的水平上被检测到。将出生后第4-6天的大鼠暴露于1.2%异氟醚或2.1%七氟醚中1-6小时，观察其即刻和延迟效应。与七氟醚暴露相比，异氟醚暴露与较弱的癫痫样脑电模式有关。在青少年时期，面对新的环境，七氟醚暴露的大鼠--但不是异氟醚暴露的大鼠--比未暴露的大鼠花费更多的时间处于不动状态。Na+-K+-2Cl-转运蛋白共转运体抑制剂布美他尼可显著降低七氟醚的脑电(55.5±12.80 S vs.14.86±7.03 S，均值±SE，P=0.014，n=6-7)和自发行为(F(2，39)=4.43，P=0.018)。布美他尼可减弱异氟醚诱导的大脑皮层caspase-3的激活(F(2，23)=22.697，P=0.001)，并防止感觉运动门控功能的损害(F(2，36)=5.978，P=0.006)。这些发现结合我们之前报道的结果表明，异氟醚和七氟烷通过类似的机制产生发育效应，包括麻醉剂诱导的神经元活动增加。同时，它们的效果不同表明，它们对新生儿麻醉的中介机制和相对安全性也不同。
The general anesthetics isoflurane and sevoflurane cause developmental abnormalities in neonatal animal models via incompletely understood mechanisms. Despite many common molecular targets, isoflurane and sevoflurane exhibit substantial differences in their actions. We sought to determine whether these differences can also be detected at the level of neurodevelopmental effects. Postnatal day 4–6 rats were exposed to 1.2% isoflurane or 2.1% sevoflurane for 1–6 hrs and studied for immediate and delayed effects. Isoflurane exposure was associated with weaker seizure-like electroencephalogram patterns than sevoflurane exposure. Confronted with a new environment at a juvenile age the sevoflurane- but not isoflurane-exposed rats spent significantly more time in an “immobile” state than unexposed rats. Electroencephalographic (55.5±12.80 s vs. 14.86 ± 7.03 s, mean± SE, P = 0.014, n = 6–7) and spontaneous behavior (F(2,39)= 4.43, P=0.018) effects of sevoflurane were significantly diminished by pretreatment with the Na+–K+–2Cl– co-transporter inhibitor bumetanide, whereas those of isoflurane were not . Pretreatment with bumetanide, however, diminished isoflurane-induced activation of caspase-3 in the cerebral cortex (F(2,23)= 22.697, P=0.001) and prevented impairment in sensorimotor gating function (F(2,36)= 5.978, P= 0.006). These findings in combination with our previously reported results suggest that isoflurane and sevoflurane produce developmental effects acting via similar mechanisms that involve an anesthetic induced increase in neuronal activity. At the same time differences in their effects suggest differences in the mediating mechanisms and in their relative safety profile for neonatal anesthesia.