Background: Blocked glycogen breakdown in McArdle disease impairs oxidative as well as anaerobic metabolism, but the contribution of impaired oxidative phosphorylation to everyday symptoms of McArdle disease remains poorly defined. Objective: To evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease. Design: Assessment of exercise and oxidative capacity (VO2) before and after the spontaneous "second wind" and with a glucose infusion after a spontaneous second wind. Patients: Eight patients with complete myophosphorylase deficiency and 1 unique patient with 3% of normal myophosphorylase activity. Main Outcome Measures: Work capacity, VO2, heart rate, cardiac output. Results: All patients with complete myophosphorylase deficiency (1) had low peak VO2 (mean±SD, 13.0±2.0 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise; (2) achieved a spontaneous second wind with increased exercise capacity between 8 and 12 minutes of exercise due to a more than 25% increase in peak VO2 (16.5±3.1 mL · kg-1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20% increase in oxidative capacity (VO2, 19.9±3.9 mL · kg-1 min-1). In the patient with residual myophosphorylase, VO2 (22.2 mL · kg-1 min-1) in the first 6 to 8 minutes of exercise was approximately 2-fold higher than the mean of patients lacking myophosphorylase, and no significant improvement in exercise and oxidative capacity accompanied prolonged exercise or glucose infusion. Conclusions: First, the spontaneous second wind and the glucose-induced second second wind in McArdle disease are due to substrate-dependent increases in muscle oxidative capacity. Second, by providing glycogen-derived pyruvate, a small amount of residual myophosphorylase activity normalizes the oxidative deficit of complete myophosphorylase deficiency and virtually eliminates the spontaneous second wind and glucose-induced second second wind.
ASJC Scopus subject areas
- Arts and Humanities (miscellaneous)
- Clinical Neurology