title: Effects of halothane and sevoflurane on inhibitory neurotransmission to medullary expiratory neurons in a decerebrate dog model.
abstract: BACKGROUND
  In canine expiratory bulbospinal neurons, 1 minimum alveolar concentration (MAC) halothane and sevoflurane reduced the glutamatergic excitatory drive at a presynaptic site and enhanced the overall gamma-aminobutyric acid (GABA)-mediated inhibitory input. The authors investigated if this inhibitory enhancement was mainly caused by postsynaptic effects.
  
  
  METHODS
  Two separate anesthetic studies were performed in two sets of decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC halothane or sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline. Complete blockade of GABAA-mediated inhibition with bicuculline was used to assess the prevailing overall inhibitory input to the neuron. The neuronal response to muscimol was used to estimate the anesthetic effect on postsynaptic GABAA receptor function.
  
  
  RESULTS
  Halothane at 1 MAC depressed the spontaneous activity of 12 expiratory neurons 22.2 +/- 14.8% (mean +/- SD) and overall glutamatergic excitation 14.5 +/- 17.9%. Overall GABA-mediated inhibition was enhanced 14.1 +/- 17.9% and postsynaptic GABAA receptor function 74.2 +/- 69.2%. Sevoflurane at 1 MAC depressed the spontaneous activity of 23 neurons 20.6 +/- 19.3% and overall excitation 10.6 +/- 21.7%. Overall inhibition was enhanced 15.4 +/- 34.0% and postsynaptic GABAA receptor function 65.0 +/- 70.9%. The effects of halothane and sevoflurane were not statistically different.
  
  
  CONCLUSIONS
  Halothane and sevoflurane at 1 MAC produced a small increase in overall inhibition of expiratory premotor neuronal activity. The increase in inhibition results from a marked enhancement of postsynaptic GABAA receptor function that is partially offset by a reduction in presynaptic inhibitory input by the anesthetics.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee 53295, USA.
authors.forename: Astrid G
authors.initials: AG
authors.lastname: Stucke
authors.forename: Eckehard A E
authors.initials: EA
authors.lastname: Stuth
authors.forename: Viseslav
authors.initials: V
authors.lastname: Tonkovic-Capin
authors.forename: Mislav
authors.initials: M
authors.lastname: Tonkovic-Capin
authors.forename: Francis A
authors.initials: FA
authors.lastname: Hopp
authors.forename: John P
authors.initials: JP
authors.lastname: Kampine
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Zuperku
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D004285:Dogs; D006221:Halothane / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D000077149:Sevoflurane; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D011963:Receptors, GABA-A; D000077149:Sevoflurane; D006221:Halothane