03 | The muscle out of breath? Limitations and adaptations in chronic diseases

Angèle N. Merlet^1|2, L.A Messonnier^3|4, L. Féasson^1|2 | ¹Unité de Myologie, Service de Physiologie Clinique et de l'Exercice, Centre Référent Maladies Neuromusculaires Rares – Euro-NmD, Hôpital Universitaire de Saint-Etienne, Saint-Etienne, France; ²Laboratoire Interuniversitaire de Biologie de la Motricité, EA 7424, F-42023, Université de Lyon, UJM-Saint- Etienne, France; ³Univ. Savoie Mont Blanc, Laboratoire Interuniversitaire de Biologie de la Motricité, Chambéry, France; ⁴Institut Universitaire de France (IUF).

Skeletal muscle demonstrates remarkable plasticity in response to physiological stimuli such as exercise and hypoxia. Chronic diseases like chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and obstructive sleep apnea syndrome (OSAS) result in chronic or intermittent hypoxia, impairing oxygen delivery to muscle tissue. Sickle cell disease (SCD), a genetic hemoglobinopathy, represents a unique model characterized by a complex hypoxic environnement (chronic, acute, and intermittent) stemming from severe chronic hemolytic anemia and recurrent vaso-occlusive crises. These hypoxic conditions induce profound alterations in skeletal muscle, mostly including fiber-type switching, atrophy, reduced capillarization, and impaired oxidative metabolism. The extent of these changes appears to depend on the nature and severity of hypoxia, as well as the degree of physical inactivity. In COPD and CHF, exercise training is well established to mitigate muscle dysfunction. Conversely, in SCD, physical activity was long considered risky due to fears of provoking vaso-occlusive events. However, our research group conducted a randomized controlled trial demonstrating that moderate-intensity endurance training is not only safe in individuals with SCD, but also enhances physical capacity and attenuates muscle alterations. These findings pave the way for novel therapeutic strategies based on exercise to improve muscle structure and quality of life in this population. In contrast, the effects of exercise training on skeletal muscle structure in patients with OSAS remain unexplored, highlighting a critical gap in the current understanding of muscle adaptation in hypoxia-related disorders.