Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity

Background We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance. Methods and results Total body O2 uptake (VO2peak) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO2peak (15.1±1.1 versus 28.1±2.3 mL·kg-1·min-1, P<.001) and capillary to fiber ratio (1.09±0.05 versus 1.40±0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups. Conclusions Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO2peak observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.