Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

Objectives. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. Background. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. Methods. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New Yolk Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (Vo(2)) during cycle ergometrg, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. Results. Peak Vo(2) and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.001). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p less than or equal to 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs, 1.05 +/- 0.08, p = 0.019). Peak Vo(2) was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak Vo(2), resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in patients. None of the skeletal muscle characteristics examined correlated with exercise capacity in control subjects, Conclusions. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal muscle and local as well as systemic exercise performance. There are fewer slow twitch fibers, smaller fast twitch fibers and lower succinate dehydrogenase activity. The latter finding suggests that mitochondrial content of muscle is reduced in heart failure and that impaired aerobic-oxidative capacity may play a role in the limitation of systemic exercise capacity.