Department of Anesthesiology, University of Florida, Gainesville, Florida 32610-0254, USA.
Anesthesiology. 2013 Aug;119(2):358-64. doi: 10.1097/ALN.0b013e318291c04e.
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. The authors sought to determine whether these differences can also be detected at the level of neurodevelopmental effects.
Postnatal rats, 4-6 days old, were exposed to 1.2% isoflurane or 2.1% sevoflurane for 1-6 h 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-exposed rats spent significantly more time in an "immobile" state than unexposed rats. Electroencephalographic (mean ± SE, 55.5 ± 12.80 s vs. 14.86 ± 7.03 s; 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 cotransporter inhibitor bumetanide, whereas those of isoflurane were not. Pretreatment with bumetanide, however, diminished isoflurane-induced activation of caspase-3 in the cerebral cortex (F(2,8) = 22.869; P = 0.002) and prevented impairment in sensorimotor gating function (F(2,36) = 5.978; P = 0.006).
These findings in combination with results previously reported by the authors 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.
全身麻醉剂异氟烷和七氟烷通过尚未完全阐明的机制在新生动物模型中引起发育异常。尽管有许多共同的分子靶点，但异氟烷和七氟烷在作用上存在显著差异。作者试图确定这些差异是否也可以在神经发育效应水平上被检测到。
4-6 天大的新生大鼠暴露于 1.2%异氟烷或 2.1%七氟烷中 1-6 小时，并研究即时和延迟效应。
异氟烷暴露与比七氟烷暴露更弱的癫痫样脑电图模式相关。在幼年时期面对新环境时，七氟烷暴露的大鼠比未暴露的大鼠在“不动”状态下花费的时间明显更多。七氟烷暴露的大鼠的脑电图（平均值±SE，55.5±12.80 秒与 14.86±7.03 秒；P=0.014；n=6-7）和自发行为（F(2,39)=4.43；P=0.018）效应显著被 Na-K-2Cl 协同转运蛋白抑制剂布美他尼预处理所减弱，而异氟烷的则没有。然而，布美他尼预处理减弱了异氟烷诱导的大脑皮质中 caspase-3 的激活（F(2,8)=22.869；P=0.002），并防止了感觉运动门控功能的损害（F(2,36)=5.978；P=0.006）。
这些发现与作者先前报告的结果相结合，表明异氟烷和七氟烷通过类似的机制产生发育效应，这些机制涉及麻醉诱导的神经元活动增加。同时，它们作用的差异表明介导机制和它们对新生儿麻醉的相对安全性特征存在差异。
