Effects of Sevoflurane on Excitatory Neurotransmission to Medullary Expiratory Neurons and on Phrenic Nerve Activity in a Decerebrate Dog Model

Background: Sevoflurane is a new volatile anesthetic with a pronounced respiratory depressant effect. Synaptic neurotransmission in canine expiratory bulbospinal neurons is mainly mediated by excitatory N-methyl-d-aspartatic acid (NMDA) receptor input and modulated by inhibitory [gamma]-aminobutyric acid type A (GABAA) receptors. The authors investigated the effect of sevoflurane on these mechanisms in decerebrate dogs.

Methods: Studies were performed in decerebrate, vagotomized, paralyzed and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 minimum alveolar concentration (MAC; 2.4%) sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the glutamate agonist NMDA and the GABAA receptor blocker bicuculline in a two-part protocol. First, complete blockade of the GABAAergic mechanism by bicuculline allowed differentiation between the effects of sevoflurane on overall GABAAergic inhibition and on overall glutamatergic excitation. In a second step, the neuronal response to exogenous NMDA was used to estimate sevoflurane's effect on postsynaptic glutamatergic neurotransmission.

Results: One minimum alveolar concentration sevoflurane depressed the spontaneous activity of 16 expiratory neurons by 36.7 +/- 22.4% (mean +/- SD). Overall glutamatergic excitation was depressed 19.5 +/- 16.2%, and GABAAergic inhibition was enhanced 18.7 +/- 20.6%. However, the postsynaptic response to exogenous NMDA was not significantly altered. In addition, 1 MAC sevoflurane depressed peak phrenic nerve activity by 61.8 +/- 17.7%.