In vivo determination of altered hemoglobin saturation in dogs with M-typephosphofructokinase deficiency

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myo pathy and chronic hemolysis in affected humans and dogs, the only animal mo del available, Deficient individuals have impaired glycolytic metabolism, i mpaired oxidative metabolism, and increased hemoglobin-oxygen (HbO(2)) affi nity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpos e of this study was to determine if PFK-deficient muscle has abnormal oxyge n saturation during exercise. Oxygen saturation of hemoglobin/myoglobin was measured noninvasively in skeletal muscle during progressive muscle activa tion using near-infrared spectroscopy (NIRS). Muscle metabolites were also measured using magnetic resonance spectroscopy (MRS). PFK-deficient and nor mal 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 st imulation, muscles from normal dogs showed progressive decrease in hemoglob in saturation. In contrast, PFK-deficient dogs exhibited either an increase in hemoglobin saturation or an initial decrease with no further change. PF K-deficient muscles accumulated 11.1 +/- 3.5 mmol/L of sugar phosphate whic h was not seen in normal muscle and had higher calculated [ADP] levels at e ach stimulation level, indicating impaired oxidative metabolism. These find ings are consistent with the hypothesis that these animals have impaired ox idative metabolism and impaired muscle O-2 extraction from hemoglobin due t o increased HbO(2) affinity. NIRS appears to be a useful noninvasive method of monitoring tissue oxygen saturation in normal or disease conditions. (C ) 1999 John Wiley & Sons, Inc.