Department of Anesthesiology, University of Florida, Gainesville, Florida 32610-0254, USA.
Anesthesiology. 2010 Mar;112(3):567-75. doi: 10.1097/ALN.0b013e3181cf9138.
We tested the hypothesis that in newborn rats, sevoflurane may cause seizures, neurotoxicity, and impairment in synaptic plasticity-effects that may be diminished by the Na-K-2Cl cotransporter 1 inhibitor, bumetanide.
Electroencephalography, activated caspase-3, and hippocampal long-term potentiation were measured in rats exposed to 2.1% sevoflurane for 0.5-6 h at postnatal days 4-17 (P4-P17).
Arterial blood gas samples drawn at a sevoflurane concentration of 2.1% showed no evidence of either hypoxia or hypoventilation in spontaneously breathing rats. Higher doses of sevoflurane (e.g., 2.9%) caused respiratory depression. During anesthesia maintenance, the electroencephalography exhibited distinctive episodes of epileptic seizures in 40% of P4-P8 rats. Such seizure-like activity was not detected during anesthesia maintenance in P10-P17 rats. Emergence from 3 h of anesthesia with sevoflurane resulted in tonic/clonic seizures in some P10-P17 rats but not in P4-P8 rats. Bumetanide (5 micromol/kg, intraperitoneally) significantly decreased seizures in P4-P9 rats but did not affect the emergence seizures in P10-P17 rats. Anesthesia of P4 rats with sevoflurane for 6 h caused a significant increase in activated caspase-3 and impairment of long-term potentiation induction measured at 1 and 14-17 days after exposure to sevoflurane, respectively. Pretreatment of P4 rats with bumetanide nearly abolished the increase in activated caspase-3 but did not alleviate impairment of long-term potentiation.
These results support the possibility that excitatory output of sevoflurane-potentiated gamma-aminobutyric acid type A/glycine systems may contribute to epileptogenic and neurotoxic effects in early postnatal rats.
我们测试了这样一个假设，即在新生大鼠中，七氟醚可能会引起癫痫发作、神经毒性和突触可塑性障碍，而钠钾 2 氯共转运蛋白 1 抑制剂布美他尼可能会减轻这些影响。
在出生后第 4-17 天（P4-P17），对暴露于 2.1%七氟醚 0.5-6 小时的大鼠进行脑电图、激活的半胱天冬酶-3 和海马长时程增强测量。
在自主呼吸的大鼠中，从七氟醚浓度为 2.1%的动脉血气样本中没有发现缺氧或通气不足的证据。更高剂量的七氟醚（例如 2.9%）会导致呼吸抑制。在麻醉维持期间，脑电图在 40%的 P4-P8 大鼠中显示出明显的癫痫发作期。在 P10-P17 大鼠的麻醉维持期间，没有检测到这种类似癫痫发作的活动。在七氟醚麻醉 3 小时后苏醒，一些 P10-P17 大鼠出现强直/阵挛性发作，但 P4-P8 大鼠没有。腹腔内给予布美他尼（5 微摩尔/千克）可显著减少 P4-P9 大鼠的发作，但对 P10-P17 大鼠的苏醒发作没有影响。用七氟醚麻醉 P4 大鼠 6 小时会导致激活的半胱天冬酶-3显著增加，并分别在暴露于七氟醚后 1 天和 14-17 天导致长时程增强诱导受损。P4 大鼠用布美他尼预处理几乎消除了激活的半胱天冬酶-3的增加，但不能缓解长时程增强的损害。
这些结果支持这样一种可能性，即七氟醚增强的γ-氨基丁酸 A/甘氨酸系统的兴奋性输出可能导致新生大鼠的致痫和神经毒性作用。
