# Increased Orexin by High Concentration of Sevoflurane Enhances the Suprahyoid Muscle Activity Involves in Gasping‐Like Respiration of Mice

## TL;DR

High sevoflurane concentration in mice increases orexin, which boosts muscle activity linked to gasping respiration, potentially improving survival during cardiac arrest.

## Contribution

The study identifies orexin as a key mediator linking sevoflurane-induced gasping respiration and suprahyoid muscle activation in mice.

## Key findings

- High sevoflurane concentration (2.0 MAC) elevates orexin precursor gene expression in the hypothalamus.
- Orexin administration enhances suprahyoid muscle activity even at lower sevoflurane concentrations.
- Orexin is implicated in the activation of gasping-like respiration in mice under sevoflurane exposure.

## Abstract

Gasping respiration enhances survival chances during cardiac arrest by activating the suprahyoid muscles (SHMs), which are crucial for airway dilation. We previously reported that the high concentration of sevoflurane (6.5%: 2.0 minimum alveolar concentration, MAC) leads to gasping‐like respiration in mice. Here, to understand the molecular mechanisms of this phenomenon, we compared the hypothalamic transcriptome profiles among control, 2.3% sevoflurane (0.7 MAC; eupnea), and 2.0 MAC groups and identified the differentially expressed genes (DEGs), in which hypocretin (orexin) precursor (Hcrt) gene expression was significantly elevated in the 2.0 MAC group. Notably, the intracerebroventricular administration of orexin enhanced SHM activity at 0.7 MAC. Our findings suggest that the 2.0 MAC sevoflurane‐induced increases in orexin enhance activation of SHMs resulting in the involvement of gasping respiration.