Skeletal Muscle Metabolism In Patients Research Articles

31P-NMR study of skeletal muscle metabolism in patients with chronic respiratory impairment.

To evaluate the energy metabolism of peripheral skeletal muscle during exercise in patients with chronic respiratory impairment, the 31P-nuclear magnetic resonance (NMR) spectra of forearm muscle were investigated in nine patients and nine age-matched control subjects. We calculated the phosphocreatine (PCr) to PCr + inorganic phosphate (PI) ratio, the time constant of PCr recovery and the intracellular pH. The exercise consisted of repetitive hand grips against a 2-kg load every 3 s for 6 min (0.33 W). The patients showed a marked decrease in the PCr/(PCr + PI) ratio and pH in the muscle during exercise in contrast to the control subjects whose PCr/(PCr + PI) showed a minor decrease without any change in pH. The relationship between PCr utilization and pH demonstrated that anaerobic glycolysis switched on earlier in patients with chronic respiratory impairment. A split PI peak was observed in five of nine patients during exercise. The PCr/(PCr + PI) ratio during the last minute of exercise correlated significantly with the vital capacity (% predicted), with the FEV1/FVC, with the body weight, with the maximum strength of hand grip, and with the muscle mass. The results indicate impaired oxidative phosphorylation and the early activation of anaerobic glycolysis in the muscles of patients with chronic respiratory impairment. Several factors related to chronic respiratory impairment, such as disuse, malnutrition and dysoxia, would contribute to the metabolic changes observed in the muscles examined.

31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.

Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure

Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 ± 0.1; dobutamine 2.1 ± 1.0 liters/min; p < 0.05) and increased femoral venous O 2 saturation (control 24 ± 5%; dobutamine 31 ± 2%; p < 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic V̇O 2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 ± 0.0039; dobutamine 0.0056 ± 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow.

Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow.

We and others have previously demonstrated excessive phosphocreatine (PCr) depletion and acidosis in skeletal muscle during exercise in patients with congestive heart failure (CHF). In the present study, we performed serial measurements of PCr and pH during gradually incremental flexor digitorum superficialis exercise in 22 patients with CHF and 11 age-matched controls to determine: (1) whether abnormalities were present at the same relative workloads (a comparison that would at least partially compensate for differences in muscle mass), (2) the temporable course of the metabolic changes, (3) the relationship of the metabolic findings to clinical variables, and (4) the relationship of the metabolic abnormalities to forearm blood flow. The patients with CHF had significantly lower [PCr] and pH at all submaximal levels of exercise, and these abnormalities were apparent from the onset of low-level exercise. There was considerable heterogeneity among the patients with CHF with respect to the metabolic findings, with 14 of 22 exhibiting either PCr or pH values more than 2 SDs below normal. Patients whose capacity was more limited during the protocol had lower [PCr], and especially pH, at low loads than did other patients with CHF or the control subjects. The more symptomatic patients and those with more limited bicycle exercise tolerance also had lower pH values. In contrast, there were no significant differences in forearm blood flow between the patients and controls and no relationship between forearm blood and either clinical variables or the metabolic findings. These results indicate that skeletal muscle metabolic abnormalities are present in many patients with CHF and that they are not primarily due to either muscle atrophy or impaired blood flow. These changes may explain in part the marked heterogeneity of symptom status and exercise capacity of patients with similar degrees of cardiac dysfunction.

31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure

In patients with congestive heart failure (CHF), exercise limitation correlates poorly with central hemodynamic abnormalities, suggesting that additional abnormalities in skeletal muscle blood flow or metabolism play an important pathophysiologic role. Therefore, muscle metabolism was examined by 31P nuclear magnetic resonance (NMR) at rest and during repetitive bulb squeeze exercise in 11 patients with New York Heart Association class II to IV CHF and 7 age-matched control subjects. Serial spectra were obtained at rest, at 2 levels of exercise and during recovery. At rest, the only abnormal finding was an elevated inorganic phosphate (P i) concentration (5.0 ± 1.5 vs 3.6 ± 0.4 m M, p < 0.01). At the lower exercise level, phosphocreatine (PCr) utilization, which was followed as the ratio of [PCr] ([PCr] + [P i]) , was greater (0.36 ± 0.16 vs 0.53 ± 0.10, p < 0.02), and pH fell more rapidly and to a lower value (6.38 ± 0.25 vs 6.85 ± 0.17, p < 0.001). At the higher level of exercise, the patients could not work effectively and the group differences narrowed. Compared with control subjects, acidification was disproportionately greater in relation to PCr depletion in patients, further suggesting excessive dependence on glycolytic metabolism. The P i peak was prominently double in 5 patients, indicating presence of a population of muscle fibers undergoing unusually active glycolysis. PCr resynthesis, a reflection of oxidative phosphorylation, was delayed in 4 patients. These findings indicate that in many patients with CHF, exercising muscle has marked metabolic changes consistent with impaired substrate availability and altered biochemistry.

Evidence for an Intrinsic Defect of Skeletal Muscle Metabolism in Patients with Chronic Heart Failure

Evidence for an Intrinsic Defect of Skeletal Muscle Metabolism in Patients with Chronic Heart Failure

Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators.

Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators.

Skeletal muscle metabolism in patients with malignant tumor

Skeletal muscle biopsies were taken from 43 cancer patients and 55 matched, presumably metabolically healthy controls for determinations of enzyme activities, capacity of glucose assimilation and metabolism and the incorporation rate of leucine into proteins. In muscle tissue from cancer patients the activities of the lysosomal enzymes, cathepsin-D and β-glucuronidase, were increased. Acid phosphatase activity was the same as in muscle tissue from the controls. The activities of hexokinase, phosphofructokinase, lactate dehydrogenase, and cytochrome-c-oxidase were significantly decreased. This decrease was accompanied by a decreased incorporation rate of glucose-carbon into glycogen, lactate and CO 2 . The incorporation rate of leucine into proteins was significantly decreased in cancer patients and the fractional degradation rate of proteins was increased. Amino acids caused the same degree of stimulation on the leucine incorporation rate into proteins as in the controls. The RNA concentration was unchanged in muscles from the cancer patients. The results suggest that malignant tumors provoke specific alterations of the skeletal muscle metabolism of the host. The rate of protein biosynthesis seems to be decreased together with an increased degradation rate. The capacity for glucose assimilation and metabolism is decreased indicating a disturbed energy regulation in the muscles of cancer patients.

Enzymatic pathways of pyruvate metabolism in skeletal muscle: adaptations to exercise.

Enzymatic pathways of pyruvate metabolism in skeletal muscle: adaptations to exercise.