title: Pressure reversal of anaesthesia: a synaptic mechanism.
abstract: Hyperbaric pressure induces seizures and increases anaesthetic requirements ("pressure reversal of anaesthesia"), but both pressure and anaesthetic agents depress excitatory synaptic transmission. The present study has attempted to resolve this paradox. The interaction between helium pressure to 10.1 MPa and anaesthetic agents (pentobarbitone, halothane, methoxyflurane) was investigated at a crustacean glutaminergic excitatory neuromuscular junction which can be modulated by GABA inhibition. Both pressure and the anaesthetics depressed the singly evoked excitatory junctional potential (EJP). During repetitive stimulation, both pressure and pentobarbitone antagonized their own depressant effects by enhancing tetanic potentiation. The additive enhancement at 10.1 MPa was sufficient to increase the pentobarbitone-depressed response above the corresponding normobaric level. No significant antagonism between pressure and any of the anaesthetics was observed on the properties of EJP amplitude and time course, facilitation, potentiation or inhibition. Additivity rather than antagonism is the basis for pressure reversal of anaesthetic depression at this model synapse. The functional antagonism is therefore indirect, and probably involves multiple sites of action for both pressure and anaesthetics.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kendig
authors.forename: Y
authors.initials: Y
authors.lastname: Grossman
authors.forename: M B
authors.initials: MB
authors.lastname: MacIver
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000502:physiology; D008121:Nephropidae; D009469:Neuromuscular Junction / Q000502:physiology*; D011312:Pressure; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000777:Anesthetics