Tissue oxygenation and muscular substrate turnover in two subjects with high hemoglobin oxygen affinity.

Oxygen transport to and substrate turnover in leg muscle were studied at rest and during light and heavy upright bicycle exercise in two brothers with a hereditary hemoglobinopathy associated with high oxygen affinity (P50 = 13 mmHg). Femoral venous oxygen tension was below normal and femoral venous oxygen saturation above normal at rest and during exercise. Thus, the arterial-femoral venous oxygen saturation difference was decreased. Despite a compensatory increase in hemoglobin concentration, the arterial-femoral venous oxygen content difference tended to be below normal at heavy exercise. Approximately 25% of the oxygen was delivered via the abnormal hemoglobin at relative heavy exercise. Arterial lactate levels, lactate release, and muscle lactate concentration were not increased at any level of exercise. Glucose, alanine, pyruvate, and glycerol turnover were essentially normal, but the glycogen and creatine phosphate stores were abnormally depleted at the termination of heavy exercise. The exercise electrocardiogram (ECG) was normal, indicating that myocardial oxygenation was adequate. Muscle-surface oxygen pressure fields were normal at rest (not investigated during exercise). It is concluded that the high oxygen affinity of the hemoglobin in our two subjects did not lead to heart or skeletal muscle hypoxia during heavy exercise, as judged from the ECG and from the leg lactate turnover. Despite the lack of evidence for muscle hypoxia, the subjects experienced leg muscle fatigue and the creatine phosphate and glycogen stores were depleted more than normally.