Hypercapnic Respiratory Failure-Driven Skeletal Muscle Dysfunction: It Is Time for Animal Model-Based Mechanistic Research.

Dysfunction of locomotor muscles is frequent in chronic pulmonary diseases and strongly associated with worse outcomes including higher mortality. Although these associations have been corroborated over the last decades, there is poor mechanistic understanding of the process, in part due to the lack of adequate animal models to investigate this process. Most of the mechanistic research has so far been accomplished using relevant individual stimuli such as low oxygen or high CO2 delivered to otherwise healthy animals as surrogates of the phenomena occurring in the clinical setting. This review advocates for the development of a syndromic model in which skeletal muscle dysfunction is investigated as a comorbidity of a well-validated pulmonary disease model, which could potentially allow discovering meaningful mechanisms and pathways and lead to more substantial progress to treat this devastating condition.