Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

Background: Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of γ-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. Methods: In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the γ-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. Results: Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. Conclusion: Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Botzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Botzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. γ-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.