Effects of riluzole on sevoflurane-induced gasping in adult mice

The inhalation of a high sevoflurane concentration under hyperoxia induces gasping, similar to the breathing patterns observed during hypoxia-induced gasping in mice. This observation, coupled with the understanding that burster neurons in the pre-Bötzinger complex, which rely on a persistent sodium current, play a crucial role in generating hypoxia-induced gasping, led us to investigate whether sevoflurane-induced gasping could be triggered by activating this current within the brainstem. To this end, we evaluated the dose-dependent effects of intraperitoneal administration of riluzole, a blocker of persistent sodium channels, on sevoflurane-induced gasping in adult mice. We used ten trachealy intubated, spontaneously breathing, sevoflurane-anesthetized mice. Seven mice randomly received three doses of intraperitoneal riluzole (6, 12, and 18 mg/kg ip) with an interval of approximately 4 wk. The test trials to elicit the sevoflurane-induced gasping were conducted before and after administering each dose of riluzole by a sudden rise in inspired concentration of sevoflurane from 0.8 MAC (minimum alveolar concentration; 2.5%-2.7%) to 2 MAC (6.4%-6.6%). In the other three mice, the test trials for eliciting the hypoxia-induced gasping were performed before and after administering 18 mg/kg riluzole. The administration of the increasing dose of riluzole demonstrated an apparent and dose-dependent attenuation of sevoflurane-induced gasping. The administration of 18 mg/kg of riluzole completely abolished the hypoxia-induced gasping. These results indicate that sevoflurane-induced gasping, like hypoxia-induced gasping, could be generated by activating a persistent sodium current within the brainstem.NEW & NOTEWORTHY The inhalation of a high sevoflurane concentration induces specific ventilation similar to hypoxia-induced gasping. Riluzole is known to inhibit hypoxia-induced gasping dose-dependently by blocking persistent sodium channels. This study showed that riluzole dose-dependently attenuates sevoflurane-induced gasping in mice. Persistent sodium channels could be important in generating sevoflurane- and hypoxia-induced gasping.