Department of Anesthesiology, University of Florida, Gainesville, Florida 32610-0254, USA.
Anesthesiology. 2012 Oct;117(4):791-800. doi: 10.1097/ALN.0b013e318266c62d.
The authors sought to determine whether subjects with pathophysiological conditions that are characterized by increased concentrations of aldosterone have increased susceptibility to the side effects of neonatal anesthesia with sevoflurane.
Postnatal day 4-20 (P4-P20) rats were exposed to sevoflurane, 6% and 2.1%, for 3 min and 60-360 min, respectively. Exogenous aldosterone was administered to imitate pathophysiological conditions with increased concentrations of aldosterone.
Six hours of anesthesia with sevoflurane on P4-P5 rats resulted in a more than 30-fold increase in serum concentrations of aldosterone (7.02 ± 1.61 ng/dl vs. 263.75 ± 22.31 ng/dl, mean ± SE, n = 5-6) and reduced prepulse inhibition of the acoustic startle response (F(2,37) = 5.66, P < 0.001). Administration of exogenous aldosterone during anesthesia with sevoflurane enhanced seizure-like electroencephalogram patterns in neonatal rats (48.25 ± 15.91 s vs. 222.00 ± 53.87 s, mean ± SE, n = 4) but did not affect electroencephalographic activity in older rats. Exogenous aldosterone increased activation of caspase-3 (F(3,28) = 11.02, P < 0.001) and disruption of prepulse inhibition of startle (F(3,46) = 6.36; P = 0.001) caused by sevoflurane. Intracerebral administration of oxytocin receptor agonists resulted in depressed seizure-like electroencephalogram patterns (F(2,17) = 6.37, P = 0.009), reduced activation of caspase-3 (t(11) = 2.83, P = 0.016), and disruption of prepulse inhibition of startle (t(7) = -2.9; P = 0.023) caused by sevoflurane.
These results suggest that adverse developmental effects of neonatal anesthesia with sevoflurane may involve both central and peripheral actions of the anesthetic. Subjects with increased concentrations of aldosterone may be more vulnerable, whereas intracerebral oxytocin receptor agonists may be neuroprotective.
作者旨在确定那些病理生理状态下醛固酮浓度升高的患者是否更容易受到七氟醚新生儿麻醉副作用的影响。
4-20 日龄（P4-P20）大鼠分别暴露于七氟醚 6%和 2.1%中 3 分钟和 60-360 分钟。给予外源性醛固酮以模拟病理生理状态下醛固酮浓度升高的情况。
4-5 日龄大鼠接受 6 小时七氟醚麻醉后，血清醛固酮浓度增加了 30 多倍（7.02±1.61ng/dl 比 263.75±22.31ng/dl，均数±SE，n=5-6），声刺激惊跳反射的前脉冲抑制作用减弱（F（2，37）=5.66，P<0.001）。七氟醚麻醉期间给予外源性醛固酮可增强新生大鼠的癫痫样脑电图模式（48.25±15.91s 比 222.00±53.87s，均数±SE，n=4），但对老年大鼠的脑电图活动没有影响。外源性醛固酮增加了七氟醚引起的 caspase-3 激活（F（3，28）=11.02，P<0.001）和惊跳反射前脉冲抑制作用的破坏（F（3，46）=6.36；P=0.001）。给予脑室内催产素受体激动剂可使七氟醚引起的癫痫样脑电图模式减弱（F（2，17）=6.37，P=0.009），降低 caspase-3 激活（t（11）=2.83，P=0.016），并破坏惊跳反射前脉冲抑制（t（7）=-2.9；P=0.023）。
这些结果表明，七氟醚新生儿麻醉的不良发育影响可能涉及麻醉的中枢和外周作用。醛固酮浓度升高的患者可能更容易受到影响，而脑室内催产素受体激动剂可能具有神经保护作用。
