Key result
Idiopathic PAH links to abnormal skeletal muscle bioenergetics despite normal mitochondrial function, suggesting impaired oxygen delivery.
Why the study?
Impaired exercise capacity in IPAH patients may be partly due to primary mitochondrial OXPHOS dysfunction in skeletal muscle, which remains unclear.
Observational (n=9)
Impaired exercise capacity in IPAH patients is associated with abnormal skeletal muscle bioenergetics likely due to impaired oxygen delivery rather than primary mitochondrial OXPHOS dysfunction.
May implicate oxygen delivery over mitochondrial defects in IPAH exercise limitation; hypothesis-generating, needs prospective trials.
Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P‐magnetic resonance spectroscopy (31P‐MRS) and laboratory muscle biopsy analysis. 31P‐MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.
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Sithamparanathan et al. (2018) conducted an observational in Idiopathic pulmonary arterial hypertension (n=9). Idiopathic pulmonary arterial hypertension was evaluated on Skeletal muscle bioenergetics and mitochondrial oxidative phosphorylation function. Patients with idiopathic pulmonary arterial hypertension showed abnormal skeletal muscle bioenergetics on 31P-MRS but normal OXPHOS function on biopsy, suggesting impaired oxygen delivery.
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