B-30 Free Communication/Poster - Oxygen Kinetics: MAY 27, 2009 1:00 PM - 6:00 PM ROOM: Hall 4F
In McArdle disease (MD), complete absence of myophosphorylase (MP) blocks glycogen breakdown, thus restricting anaerobic metabolism. We have shown that impaired glycogenolysis also limits substrate availability for oxidative metabolism. Since patients lack the ability to increase lactate during exercise, an additional factor in impaired O2 utilization may be an absent Bohr effect -the rightward shift in the oxyhemoglobin dissociation curve caused by the increase in lactic acid and H+, that facilitates O2 extraction during intensive exercise.
PURPOSE: To assess the importance of the Bohr effect on muscle O2 extraction employing patients with typical McArdle disease (glycogenolysis completely blocked) and an unusual patient with a small amount of residual MP who we have shown to have a 2-fold higher peak VO2 than typical patients.
METHODS: Three MD patients with complete MP deficiency, 1 variant MD patient with 3% of normal MP activity, and 13 healthy control subjects performed an aerobic forearm exercise test, consisting of 5 sec isometric grip force alternating with 5 sec of rest for 6 min. We measured lactate, pH, partial pressure of O2 (pO2) and CO2 (pCO2) in effluent venous blood at rest, and at the end of exercise with a target grip force of 50% of maximal voluntary contraction.
RESULTS: Plasma lactate decreased during exercise in typical MD patients (0.6 ± 0.1 to 0.5 ± 0.1 mmol/L), but increased slightly in the variant MD patient (1.03 to 1.14 mmol/L) and substantially in controls (0.9 ± 0.2 to 2.9 ± 1.1 mmol/L). Correspondingly, pH decreased in controls (7.37 ± 0.02 to 7.28 ± 0.04) and to a lesser degree in the variant MD patient (7.35 to 7.32), but increased in typical MD patients (7.38 ± 0.04 to 7.40 ± 0.03). During exercise, venous pO2 was increased in typical MD patients compared with controls (37.3 ± 3.1 vs. 26.8 ± 2.6 mmHg). The pO2 level in the variant MD patient was comparable to controls (26.0 mmHg). pCO2 was increased at the end of exercise in both controls (68.2 ± 9.0 mmHg) and variant MD patient (55 mmHg), compared with typical MD patients (39.3 ± 9.3 mmHg).
CONCLUSIONS: This study suggests that absence of the Bohr effect in typical MD patients may contribute to impaired O2 extraction. Minimal residual MP activity in the variant MD patient is sufficient to normalize O2 utilization during exercise facilitated by the Bohr effect.