Effects of sevoflurane on excitatory neurotransmission to medullary expiratory neurons and on phrenic nerve activity in a decerebrate dog model.

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  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 1300217 Publication Model: Print Cited Medium: Print ISSN: 0003-3022 (Print) Linking ISSN: 00033022 NLM ISO Abbreviation: Anesthesiology Subsets: MEDLINE
    • Publication Information:
      Publication: Philadelphia Pa : Lippincott Williams & Wilkins
      Original Publication: Philadelphia : American Society of Anesthesiologists
    • Subject Terms:
      Anesthetics, Inhalation/*pharmacology ; Decerebrate State/*physiopathology ; Excitatory Amino Acids/*physiology ; Medulla Oblongata/*cytology ; Methyl Ethers/*pharmacology ; Neurons/*drug effects ; Phrenic Nerve/*drug effects ; Respiratory Mechanics/*drug effects ; Synaptic Transmission/*drug effects; Animals ; Dogs ; Excitatory Amino Acid Antagonists/pharmacology ; Halothane/pharmacology ; Medulla Oblongata/drug effects ; Pulmonary Alveoli/metabolism ; Receptors, GABA-A/drug effects ; Receptors, N-Methyl-D-Aspartate/drug effects ; Sevoflurane
    • Abstract:
      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.
    • Grant Information:
      GM59234-01 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Anesthetics, Inhalation)
      0 (Excitatory Amino Acid Antagonists)
      0 (Excitatory Amino Acids)
      0 (Methyl Ethers)
      0 (Receptors, GABA-A)
      0 (Receptors, N-Methyl-D-Aspartate)
      38LVP0K73A (Sevoflurane)
      UQT9G45D1P (Halothane)
    • Publication Date:
      Date Created: 20010817 Date Completed: 20010830 Latest Revision: 20190628
    • Publication Date:
      20221213
    • Accession Number:
      10.1097/00000542-200108000-00034
    • Accession Number:
      11506124