Spontaneous "second wind" and glucose-induced second "second wind" in McArdle disease: oxidative mechanisms

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 (.VO(2)) 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,.VO(2), heart rate, cardiac output.

RESULTS: All patients with complete myophosphorylase deficiency (1) had low peak.VO(2) (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.VO(2) (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 (.VO(2), 19.9 +/- 3.9 mL. kg(-1). min(-1)). In the patient with residual myophosphorylase,.VO(2) (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.