Oxidative Metabolism During Forearm Exercise in McArdle Disease (P6.109)

OBJECTIVE: to assess muscle oxidative metabolism in McArdle disease (MD) during prolonged aerobic forearm exercise. BACKGROUND: Blocked glycogenolysis in MD restricts oxidative metabolism and oxygen (O2) extraction; after 6-9 minutes of sustained cycle exercise patients develop a spontaneous “second wind” with enhanced exercise capacity attributable to increased muscle oxidative capacity and efficiency of O2 uptake - but limited data suggests oxidative metabolism remains substrate-limited. DESIGN/METHODS: Subjects performed 5 seconds of isometric handgrip at 50% of maximal voluntary contraction alternating with 5 seconds of rest for 15 minutes. Anticubital venous blood was sampled at rest and at 3, 6, 9, 12, and 15 minutes of exercise to measure pO2 (reflecting O2 uptake), pCO2 (reflecting TCA cycle function) and ammonia (reflecting impaired ADP phosphorylation). Results in 8 patients with typical MD (no residual myophosphorylase) were compared to an atypical MD patient with trace myophosphorylase activity (n=1), and to healthy control subjects (n=8). RESULTS: Venous pO2 in typical MD patients was abnormally high during exercise before normalizing after 6-9 minutes of exercise. Ammonia levels peaked between 3 and 6 minutes of exercise and declined thereafter consistent with enhanced oxidative phosphorylation. pCO2 remained low throughout exercise despite trending upwards in minutes 9-15. In contrast to typical MD patients, the patient with trace residual myophosphorylase had normal pO2 and pCO2 in exercise. CONCLUSIONS: These results indicate that a second wind occurs during isolated muscle exercise as marked by normalization of venous pO2 and a reduction in ammonia levels between 6 and 9 minutes of exercise mimicking the timeframe of enhanced oxidative metabolism in cycle exercise; but low pCO2 (implying impaired TCA cycle function) persists after the second wind. A minor level of preserved myophosphorylase in atypical MD normalizes oxidative metabolism indicating that small levels of glycogenolysis are sufficient to support TCA cycle flux and oxidative phosphorylation. Study Supported by: The Muscular Dystrophy Association and The Giant Tiger Foundation Disclosure: Dr. Haller has nothing to disclose. Dr. Phillips has nothing to disclose. Dr. Newby has nothing to disclose. Dr. Wyrick has nothing to disclose. Dr. Heinicke has nothing to disclose.