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 (GABA(A)) 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 GABA(A) receptor blocker bicuculline in a two-part protocol. First, complete blockade of the GABA(A)ergic mechanism by bicuculline allowed differentiation between the effects of sevoflurane on overall GABA(A)ergic 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 GABA(A)ergic 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%.


CONCLUSIONS
In the authors' in vivo expiratory neuronal model, the depressive effect of sevoflurane on synaptic neurotransmission was caused by a reduction of presynaptic glutamatergic excitation and an enhancement of GABA(A)ergic inhibition. The effects on expiratory neuronal activity were similar to halothane, but sevoflurane caused a stronger depression of phrenic nerve activity than halothane.
Stucke
A G
AG
Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, USA.
Stuth
E A
EA
Tonkovic-Capin
V
V
Tonkovic-Capin
M
M
Hopp
F A
FA
Kampine
J P
JP
Zuperku
E J
EJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State / Q000503:physiopathology*; D004285:Dogs; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000502:physiology*; D006221:Halothane / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology* / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D000077149:Sevoflurane; D009435:Synaptic Transmission / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D008738:Methyl Ethers; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane; D006221:Halothane