Functional, histological, and molecular adaptations of forelimb muscles in a rat model of monocrotaline-induced heart...

Histological changes in skeletal muscle after heart failure have been widely investigated in the lower limbs, including slow-to-fast fiber type transition, fast fiber-predominant atrophy, reduced capillary number, and increased collagen content. However, histological changes in the upper limb muscles remain largely unexplored. Given the prognostic significance of grip strength and upper limb muscle mass in heart failure, elucidating these changes is essential. We aimed to investigate histological changes in forelimb muscles in a rat model of monocrotaline (MCT)-induced heart failure. Rats were assigned to control (vehicle-injected) or heart failure (MCT-injected) groups. Grip strength was measured on day 27, and histological analyses of the biceps brachii (BiB) and flexor digitorum profundus (FDP) were performed on day 28. Grip strength significantly reduced in the heart failure group. Both BiB and FDP exhibited significant atrophy of fast fibers without changes in slow fiber size. The BiB showed a reduced capillary-to-muscle fiber ratio and no change in fiber type, whereas the FDP showed a shift toward a faster fiber phenotype and no change in capillary number. Collagen content remained unchanged in both muscles. MCT-induced heart failure leads to fast fiber-specific atrophy in forelimb muscles, with muscle-specific differences in capillary and fiber type adaptations. These changes may underlie the impaired upper limb muscle functions in heart failure. While some findings are consistent with those in lower limb muscles, others differ, suggesting region- and muscle-specific responses. Thus, findings from a single muscle cannot necessarily be extrapolated to all skeletal muscles.