Abnormalities in skeletal muscle metabolism in cyanotic patients with congenital heart disease: a 31P nuclear magnetic resonance spectroscopy study.

1. Exercise tolerance is impaired in congenital heart disease. To examine the possible contribution of abnormalities in skeletal muscle bioenergetics, we used 31P nuclear magnetic resonance spectroscopy to investigate muscle metabolism in 10 subjects with congenital heart disease with cyanosis (median age 17.3 years) and in eight healthy age-matched control subjects. Spectra were collected from the gastrocnemius muscle at rest and during exercise and recovery. 2. In resting muscle there were significant elevations in cytosolic pH and in the cytosolic concentration of inorganic phosphate in the patients, and a strong positive correlation between cytosolic pH and blood haemoglobin concentration in all subjects. 3. During plantar flexion exercise the patients showed increased phosphocreatine depletion and cytosolic acidification over a shorter duration of exercise. The rise in calculated cytosolic ADP concentration was similar in both groups. 4. After cessation of exercise, the recovery half-times of phosphocreatine, ADP and phosphate were two to three times longer in the patients, and the initial rate of phosphocreatine resynthesis (a measure of the rate of mitochondrial ATP synthesis) was half the control value, consistent with a reduction in the effective maximum rate of oxidative ATP synthesis (expressed per volume of muscle). Also, recovery was faster in the young control subjects than in our earlier studies of older healthy control subjects. 5. The high phosphate concentration in resting muscle and the abnormalities found in exercise and recovery are consistent with a decrease in oxidative ATP synthesis due to reduced oxygen delivery by the blood in chronic hypoxaemia. The correlation between cytosolic pH and haemoglobin concentration remains to be explained.