Slow and fast locomotor muscle adaptations to Sustained Intermittent Hypoxaemia

Episodic hypoxaemia is associated with muscle dysfunction in respiratory insufficiencies, but its effects depend on the hypoxia/reoxygenation pattern. Sustained Intermittent Hypoxemia (SIH) characterizes a large subgroup of COPD patients, yet muscle adaptations to SIH remain poorly known. We used a mouse model of SIH (FiO₂: 10%, 8 h/day) and analysed myofibre structural, muscle mass regulators, and myogenic markers in fast and slow-twitch hindlimb muscles. SIH induced an increase in haematocrit. At 35 days, Soleus cross-sectional area increased predominantly in slow-twitch fibres, but not in the fast Tibialis Anterior (TA) muscle. HIF1 target gene expression was increased at early timepoints with muscle-type-specific differences. While myostatin plasma levels were decreased, myostatin receptor and atrogene expression differed between muscles at baseline and upon SIH. Myod1 and Myog expression decreased over time in the TA only . In conclusion, SIH induces muscle-type-specific adaptations, promoting hypertrophy in slow-twitch muscle while impairing myogenic regulation in fast-twitch muscle.