Contribution of intrinsic skeletal muscle changes to ³¹P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure

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 (peak V̇O₂, 15.4 ± 4.7 ml/kg/min; ejection fraction, 20 ± 7%) and on eight normal subjects. Biopsies were analyzed for fiber type and area, capillarity, citrate synthase, phosphofructokinase, lactate dehydrogenase, and β-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 (P(i)/PCr) to systemic V̇O₂ 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 (normal subjects, 22.7 ± 10.1; heart failure, 33.1 ± 11.1%; p < 0.05), atrophy or type IIa (normal subjects, 5,477 ± 1,109; heart failure, 4,239 ± 2,247 μm²; p < 0.05) and type IIb fibers (normal subjects, 5,957 ± 1,488; heart failure, 4,144 ± 945 μm²; p < 0.01), and decreased activity of β-hydroxyacyl CoA dehydrogenase (normal subjects, 5.17 ± 1.44; heart failure, 3.67 ± 1.68 mol/kg protein/hr; p < 0.05). No significant linear correlation could be identified between the slope of the P(i)/PCr to V̇O₂ relation and muscle histochemsitry 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.