The effect of volume-overload heart failure on myosin heavy chain expression and citrate synthase activity in rodent cardiac and skeletal muscle

Jeffrey Tod Soukup


The purpose of this study was to determine the effect of myocardial volume overload (MVO) induced congestive heart failure (CHF) on myosin heavy chain (MHC) composition and citrate synthase (CS) activity in rodent cardiac and skeletal muscle. Fourteen male Sprague-Dawley rats were randomly assigned to either an experimental (CHF, n = 7) or sham-operated control (S, n = 7) group. MVO was induced by infrarenal arterio-venous (A-V) fistula and the animals were followed to decompensation. Open-field photobeam activity measurements were made in a pairwise manner of the CHF and S animals at 7, 9, and 11-weeks post-surgery. Upon clinical signs of decompensation, hemodynamic measurements were made on both the CHF and S animals to determine the extent of heart failure present. The soleus, plantaris, and extensor digitorum longus (EDL) muscles along with a portion of the left ventricle (LV) were harvested for determination of MHC composition and CS activity. In the CHF group, left ventricular end diastolic pressure (LVEDP) was significantly increased (p < 0.05) suggesting a moderate degree of heart failure. There were no differences in physical activity between the CHF and S groups at any time point. Within the skeletal muscle, only the MHC composition of the soleus was significantly (p < 0.05) altered in the CHF group, demonstrating an increase in type Ha MHC expression and a decrease in type I MHC expression. In the heart, a significant increase (p < 0.05) in LV β-MHC expression and a significant decrease (p < 0.05) in α-MHC expression were noted. There were no significant differences in CS activity for any of the skeletal muscles. However, a significant reduction (p < 0.01) in LV CS activity was noted in the CHF group. These results suggest that chronic, decompensated MVO with a moderate degree of heart failure significantly altered cardiac MHC expression and oxidative enzyme capacity and produced a reversion toward the fetal isoform. Furthermore, oxidative skeletal muscle incurred significant alterations in MHC composition that was not explained by reductions in physical activity.