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Oxidative Mechanisms

Ronald G. Haller, MD; John Vissing, MD, PhD

Arch Neurol. 2002;59:1395-1402.

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 (O₂) 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, O₂, heart rate, cardiac output.

Results  All patients with complete myophosphorylase deficiency (1) had low peak O₂ (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 O₂ (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 (O₂, 19.9 ± 3.9 mL · kg^-1· min^-1). In the patient with residual myophosphorylase, O₂ (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.

From the Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, The Veterans Affairs Medical Center, and The University of Texas Southwestern Medical Center, Dallas (Dr Haller); and the Copenhagen Muscle Research Center and Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (Dr Vissing).

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