Roles of aldosterone and oxytocin in abnormalities caused by sevoflurane anesthesia in neonatal rats.
Roles of aldosterone and oxytocin in abnormalities caused by sevoflurane anesthesia in neonatal rats.
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DOI：
10.1097/aln.0b013e318266c62d
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发表时间：
2012-10
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：
Cao W;Pavlinec C;Gravenstein N;Seubert CN;Martynyuk AE
我们研究了具有以醛固酮水平升高为特征的病理生理状况的受试者是否对七氟烷新生儿麻醉的副作用易感。出生后第4 - 20天（P4-P20）大鼠分别暴露于6%和2.1%七氟烷3 min和60 - 360 min。给予外源性醛固酮以模拟醛固酮水平升高的病理生理条件。在P4-P5用七氟烷麻醉6小时，导致血清醛固酮水平增加30倍以上（7.02 ± 1.61 ng/dl vs. 263.75 ± 22.31 ng/dl，平均值± SE，n = 5 - 6），声惊吓反应的前脉冲抑制降低（F（2，37）= 5.66，P <0.001）。在七氟烷麻醉期间给予外源性醛固酮进一步增强了新生大鼠的类脑电模式（48.25 ± 15.91 s vs. 222.00 ± 53.87 s，平均值± SE，n = 4），但对老年大鼠的脑电活动没有影响。外源性醛固酮增加了七氟醚引起的caspase-3活化（F（3，28）= 11.02，P <0.001）和惊吓前脉冲抑制的破坏（F（3，46）= 6.36; P = 0.001）。脑内给予催产素受体激动剂导致七氟烷引起的抑郁样脑电图模式（F（2，17）= 6.37，P = 0.009）、半胱天冬酶-3活化减少（t（11）= 2.83，P = 0.016）和惊恐PPI中断（t（7）=-2.9，P = 0.023）。这些结果表明，新生儿七氟烷麻醉的不良发育影响可能涉及麻醉剂的中枢和外周作用。醛固酮水平升高的受试者可能更脆弱，而脑内催产素受体激动剂可能具有神经保护作用。
We sought whether subjects with pathophysiological conditions that are characterized by elevated levels of aldosterone have increased susceptibility to the side effects of neonatal anesthesia with sevoflurane. Postnatal day 4–20 (P4–P20) rats were exposed to 6% and 2.1% sevoflurane for 3 min and 60–360 min, respectively. Exogenous aldosterone was administered to imitate pathophysiological conditions with elevated levels of aldosterone. Six hours of anesthesia with sevoflurane on P4–P5 resulted in more than 30-fold increase in serum levels 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 further 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 PPI 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 elevated levels of aldosterone may be more vulnerable, while intracerebral oxytocin receptor agonists may be neuroprotective.