Chronic Congestive Heart Failure Elicits Adaptations of Endurance Exercise in Diaphragmatic Muscle

Abstract

Background During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects. Methods and Results Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36±20 years) and 10 patients (age, 50±6 years; left ventricular ejection fraction, 18±8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; β-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43±2%, 40±2%, and 17±1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55±2%, 38±2%, and 7±2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased ( P <.0001) and myosin heavy chain IIb decreased from normal levels ( P <.001). Additionally, citrate synthase activity (normal, 0.33±0.14; heart failure, 0.54±0.21 μmol·min −1 ·mg protein −1 ; P <.05) and β-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27±0.04; heart failure, 0.38±0.02 μmol·min −1 ·mg protein −1 ; P <.05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6±4.6; heart failure,: 4.3±2.2 μmol·min −1 ·mg protein −1 ; P <.01). Conclusions In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.