Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure . D M Mancini, E Coyle, A Coggan, J Beltz, N Ferraro, S Montain, J R Wilson. Circulation. November 1989;80(5):1338-1346. Quote: Patients with heart failure frequently exhibit abnormal skeletal muscle metabolic responses to exercise, as assessed with 31P NMR. To investigate whether these metabolic abnormalities are due to intrinsic skeletal muscle changes, we performed gastrocnemius muscle biopsies on 22 patients with heart failure and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phospho-fructokinase, lactate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase activity. All patients with heart failure also underwent 31P NMR studies of their calf muscle during plantarflexion at three workloads. Muscle pH responses and the relation of the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) to systemic VO2 were then evaluated. Compared with normal subjects, patients with heart failure exhibited a shift in fiber distribution with increased percentage of the fast twitch, glycolytic, easily fatigable type IIb fibers, atrophy of type IIa and type IIb fibers, and decreased activity of beta-hydroxyacyl CoA dehydrogenase... Type IIb fibers represent fibers that are fast twitch, have a low aerobic potential, and are easily fatigued... No significant linear correlation could be identified between the slope of the Pi/PCr to VO2 relation and muscle histochemistry or enzyme activities. Similarly, no linear relation was found between intracellular pH at peak exercise and any muscle variable. These data suggest that patients with heart failure develop intrinsic skeletal muscle changes but that these intrinsic muscle changes do not contribute significantly to the abnormal skeletal muscle 31P NMR metabolic responses observed in such patients.
Serum digoxin-like immunoreactive factor (DLIF), an endogenous substance that cross-reacts with antidigoxin antibodies, was assessed (fluorescence polarization immunoassay) in children (n = 134) aged 5-16 y, who had never been treated with cardiac glycosides. DLIF was found in 50% of serum samples at a mean concentration of +/- ng/ml (range - ng/ml). Although the study population as a whole was apparently homogeneous with regard to serum sodium content, and none had clinical signs of sodium imbalance, children with DLIF showed significantly lower natraemia (p = ), higher urinary concentration (p = ) and fractional excretion (p = ) of sodium, and increased systolic blood pressure (p = ) compared with children without DLIF. Inverse correlations were found between DLIF concentration and serum sodium (p < ), urine sodium content (p < ), 24-h sodium excretion (p < ), systolic (p < ) and diastolic (p < ) blood pressure. These findings suggest that sodium handling is different in children with and without DLIF, since this material seems to be released preferably in subjects who show a trend towards negative sodium balance. Such an association suggests that DLIF may be a physiologically relevant material involved in sodium homeostasis.