Roles of Aldosterone and Oxytocin in Abnormalities Caused by Sevoflurane Anesthesia in Neonatal Rats

Abstract

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.