Anesthesiology
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Isoflurane-N2O anesthesia (as compared with halothane-N2O) reduces the cerebral blood flow (CBF) at which electroencephalographic changes occur in humans subjected to carotid occlusion. In contrast, no differences were seen in rats when cortical depolarization (instead of the electroencephalogram) was used as the ischemic marker during equi-MAC isoflurane-N2O and halothane-N2O anesthesia. To extend these findings, we used laser-Doppler flowmetry to continuously examine CBF (CBFLDF) and attempted to better define the relation between CBF and the time to depolarization (as a measure of the rate of energy depletion after ischemia). ⋯ The CBF threshold for cortical depolarization as measured by laser-Doppler flowmetry did not differ significantly between halothane-N2O- and isoflurane-N2O-anesthetized rats. There were also no important differences in the times until depolarization, other than a small difference when flow = 0. If the time to depolarization is reflects the potential ischemic injury, the it is unlikely that isoflurane-N2O conveys any protective advantage relative to halothane-N2O.
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This study examines the behavioral effects and potential neurotoxicity of sufentanil, alfentanil, and morphine after chronic daily epidural (15-day) and intrathecal (28-day) administration in dogs. ⋯ This large-animal model demonstrates the expected pharmacologic potency of these three agents and tolerance development. Based on cerebrospinal fluid and systematic histopathologic analyses, these three spinally administered agents showed no evidence of neurotoxicity over the range of doses/concentrations employed when given by the intrathecal or epidural route as compared to vehicle controls. Consideration of the toxicokinetics in this canine model suggests that it provides an appropriate test of the safety of these agents in concentrations which exceed those employed for daily intermittent epidural and intrathecal drug delivery in humans.
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Activation of the gamma-aminobutyric acidA (GABAA) receptor-ionophore complex has been reported as a possible molecular mechanism of the anesthetic action of propofol. Augmentation of GABA-induced inhibitory transmission has also been suggested as a mechanism. Because data describing this latter mechanism in mammalian neurons are few, we have examined the effects of propofol on the GABA response in central neurons of the rat. ⋯ Propofol at clinically relevant concentrations enhances the inhibitory GABAA receptor-mediated response in mammalian central neurons. The enhancement may result in reduced excitability of the neuronal network and may, consequently, contribute to the anesthetic action of the agent.