Spontaneous “Second Wind” and Glucose-Induced Second “Second Wind” in McArdle Disease: Oxidative Mechanisms


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Abstract

BackgroundBlocked 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.ObjectiveTo evaluate the oxidative implications of the spontaneous second wind and variables that influence the development of this typical feature of McArdle disease.DesignAssessment of exercise and oxidative capacity (V̇O2) before and after the spontaneous “second wind” and with a glucose infusion after a spontaneous second wind.PatientsEight patients with complete myophosphorylase deficiency and 1 unique patient with 3% of normal myophosphorylase activity.Main Outcome MeasuresWork capacity, V̇O2, heart rate, cardiac output.ResultsAll patients with complete myophosphorylase deficiency (1) had low peak V̇O2 (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 V̇O2 (16.5 ± 3.1 mL · kg−1· min−1); and (3) with glucose infusion after a spontaneous second wind, experienced a further more than 20% increase in oxidative capacity (V̇O2, 19.9 ± 3.9 mL · kg−1· min−1). In the patient with residual myophosphorylase, V̇O2 (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.ConclusionsFirst, 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.

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