Fiber-type-dependent histological changes in skeletal muscle following heart failure in rats

Skeletal muscle remodeling, including fiber atrophy, reduction in capillary number, and fibrosis, is frequently observed in patients with heart failure. However, there are arguments about which type of muscle fiber is vulnerable to heart failure induced remodeling. We aimed to determine whether histological changes in skeletal muscle following heart failure differ depending on muscle fiber type. A monocrotaline-induced rat model of heart failure was used, with vehicle-injected rats serving as controls. At 28 days post-injection, three hindlimb muscles with different fiber-type compositions-the soleus (slow-dominant), gastrocnemius (mixed), and plantaris (fast-dominant)-were harvested. Muscle fiber cross-sectional area (CSA), capillary-to-fiber ratio, and collagen content were evaluated histologically. All three muscles exhibited significant reductions in CSA of fast fibers and in capillary-to-fiber ratio, regardless of fiber-type composition. In contrast, atrophy of slow fibers was observed in the soleus and gastrocnemius, and collagen accumulation was evident in the gastrocnemius and plantaris. These results suggest that fast fiber atrophy and capillary loss are independent of fiber type, whereas slow fiber atrophy and fibrosis may depend on the fiber-type composition. Notably, the pattern and extent of histological changes differed among the muscles examined. This muscle-to-muscle variability highlights the complexity of skeletal muscle remodeling in heart failure and suggests that findings from a single muscle may not be representative of others. These findings underscore the importance of evaluating multiple muscles when one studies skeletal muscle pathology, which supports proposal of more tailored rehabilitation approaches targeting specific muscle characteristics in patients with heart failure.