Validation and Insights of Anesthetic Action in an Early Vertebrate Network

Abstract

The lamprey spinal cord is a well-characterized vertebrate network that could facilitate our understanding of anesthetic action. We tested several hypotheses concerning the lamprey's clinical application to anesthesia, and the sites/mechanisms of anesthetic action. In isolated lamprey spinal cords, minimum immobilizing concentrations (MICs) were determined for halothane, isoflurane, sevoflurane, desflurane, propofol, or the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane), applied during D-glutamate-induced fictive swimming or noxious tail stimulation. Isoflurane and propofol effects on fictive swimming were tested in the presence and absence of strychnine and/or picrotoxin. Volatile anesthetic MICs were clinically comparable. Isoflurane MIC for fictive swimming and noxious stimulus-evoked movement were the same. F6 did not produce immobility, but decreased the amplitude and phase lag of fictive swimming. Isoflurane decreased fictive swimming cycle frequency, amplitude, autocorrelation, rostrocaudal phase lag, and coherence. Strychnine and picrotoxin elicited only disorganized motor activity under isoflurane and caused small increases in MIC. The effects of propofol differed from isoflurane for all locomotor rhythm variables except amplitude. The propofol MIC was much larger in lampreys compared with mammals. However, picrotoxin reversed propofol-induced immobility by reinitiating coordinated locomotor activity and increasing MIC>8-fold. The lamprey spinal cord is a relevant and tractable vertebrate network model for anesthetic action. Isoflurane disrupts interneuronal locomotor networks. γ-Aminobutyric acid A and glycine receptors have marginal roles in isoflurane-induced immobility in lampreys. Propofol's selective γ-aminobutyric acid A receptor-mediated immobilizing mechanism is conserved in lampreys. The differential immobilizing mechanisms of isoflurane versus propofol reflect those in mammals, and further suggest different network modes of immobilizing action.