Basal Energetics and Phosphocreatine Recovery Kinetics in Ambulatory Boys With Duchenne Muscular Dystrophy.

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive condition that is characterized by muscle deterioration, loss of functional abilities, and shortened lifespan. There is growing evidence of skeletal muscle mitochondrial impairments in DMD, and ³¹phosphorous magnetic resonance spectroscopy (³¹P-MRS) provides a noninvasive marker of functional oxidative capacity of muscle. Therefore, the purpose of this study was to examine ³¹P-MRS indices of energetic status and oxidative capacity in DMD and correlate with clinical functional measures. In this study, we evaluated ambulatory participants with DMD (n = 21, 8.7 ± 1.9 years) and unaffected age-matched controls (n = 20, 9.0 ± 2.8 years) using a 3T MR system. ³¹P-MRS was used to measure relative changes in high-energy phosphates and muscle pH of the anterior compartment of the lower leg during and following isometric dorsiflexion muscle contractions (120 s rest, 60 s of contractions at 0.5 Hz, and 420 s recovery). Data were analyzed with jMRUI (v7.0), and a mono-exponential model was used to estimate the time constant (tau) of PCr recovery (PCrτ). We observed that relative concentrations of inorganic phosphate to phosphocreatine (Pi/PCr) and phosphodiesters to ATP (PDE/ATP) were elevated (p < 0.05) in DMD compared to controls, and the PCrτ recovery was slower (p < 0.01) in DMD than controls. PCrτ recovery was correlated with the distance covered in the 6-min walk test (6MWT) (ρ = -0.61, p < 0.01) and other timed functional measures (ρ = 0.54-0.67, p < 0.05). The findings from this study demonstrated that energetic status is altered and PCr recovery time is impaired in ambulatory boys with DMD indicating reduced oxidative capacity compared to unaffected controls. Overall, these findings support the use of ³¹P-MRS as a valuable noninvasive tool to evaluate skeletal muscle energetics and mitochondrial function in individuals with DMD.