In vivo magnetic resonance spectroscopy measurement of deoxymyoglobin during exercise in patients with heart failure. Demonstration of abnormal muscle metabolism despite adequate oxygenation.

Abstract

BACKGROUND Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an O2 binding protein that can indirectly assess tissue hypoxia. METHODS AND RESULTS In vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction = 20 +/- 6%; VO2 = 14.5 +/- 5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals. With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18 +/- 0.08; HF: 0.40 +/- 0.32 W-1; P < .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P = NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (Nl: 0.21 +/- 0.10; HF: 0.57 +/- 0.32 W-1; P < .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P = NS). With arterial occlusion, deoxymyoglobin was seen in all subjects. CONCLUSION Abnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.