Abstract

Background: A majority of idiopathic pulmonary arterial hypertension (IPAH) patients display persistent exercise intolerance despite new specific therapies. Whether IPAH patients exhibit peripheral muscle dysfunction that may contribute to this limitation remains unknown. We tested the hypothesis that IPAH patients’ muscle is weaker and display morphological changes compared to control subjects and that those changes partly correlate with their exercise capacity.

Objective: To characterize quadriceps function, morphology and enzymatic profile of IPAH patients.

Methods: Exercise capacity, limb muscle cross sectional area by CT scan, quadriceps strength by maximal voluntary contraction (MVC) and non-volitional magnetic stimulation of the femoral nerve (TWq), and muscle morphology and enzymatic profile by quadriceps biopsy of 10 IPAH patients were compared to 10 matched controls subjects.

Results: IPAH patients displayed lower proportion of type I muscle fibres (p=0.05), a lower MVC (p=0.05) and TWq (p=0.01) and an increased muscular phosphofructokinase/3-Hydroxyacyl-CoA-dehydrogenase ratio (p=0.05). They also tended to have lower thigh muscle cross sectional area (p=0.15). Maximal oxygen uptake correlated with quadriceps strength (R²=0.42, p=0.04) and oxygen uptake at anaerobic threshold correlated with muscle oxidative capacity assessed by oxidative enzyme level for Citrate synthase(R²=0.45, p=0.05) and 3-Hydroxyacyl-CoA-dehydrogenase (R²=0.86, p<0.01), and type I fibre capillarity (R²=0.57, p=0.02).

Conclusion: IPAH patients present significant peripheral muscle changes that partly correlated with their exercise capacity.