In vivo determination of altered hemoglobin saturation in dogs with M-type phosphofructokinase deficiency.

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myopathy and chronic hemolysis in affected humans and dogs, the only animal model available. Deficient individuals have impaired glycolytic metabolism, impaired oxidative metabolism, and increased hemoglobin-oxygen (HbO2) affinity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpose of this study was to determine if PFK-deficient muscle has abnormal oxygen saturation during exercise. Oxygen saturation of hemoglobin/myoglobin was measured noninvasively in skeletal muscle during progressive muscle activation using near-infrared spectroscopy (NIRS). Muscle metabolites were also measured using magnetic resonance spectroscopy (MRS). PFK-deficient and normal dogs were anesthetized and the cranial tibial muscles stimulated for 6 min at each of four different rates (1, 2, 4, and 8 Hz). With increasing stimulation, muscles from normal dogs showed progressive decrease in hemoglobin saturation. In contrast, PFK-deficient dogs exhibited either an increase in hemoglobin saturation or an initial decrease with no further change. PFK-deficient muscles accumulated 11.1 +/- 3.5 mmol/L of sugar phosphate which was not seen in normal muscle and had higher calculated [ADP] levels at each stimulation level, indicating impaired oxidative metabolism. These findings are consistent with the hypothesis that these animals have impaired oxidative metabolism and impaired muscle O2 extraction from hemoglobin due to increased HbO2 affinity. NIRS appears to be a useful noninvasive method of monitoring tissue oxygen saturation in normal or disease conditions.