Skeletal muscle histological remodeling precedes functional impairment in a muscle-specific manner following monocrotaline-induced heart failure in rats
摘要
Skeletal muscle remodeling in heart failure contributes to exercise intolerance and muscle weakness, but the temporal relationship between histological alterations and functional impairment remains poorly understood. We aimed to clarify whether histological changes in skeletal muscle precede the onset of functional impairment.
MethodsRats were allocated into either a normal control group (n = 21) or a monocrotaline-induced heart failure group (n = 42) and evaluated at 1, 2, or 4 weeks after injection. We assessed motor function (grip strength and exhaustive running), organ weights, and histological changes in three hindlimb muscles: the soleus (predominantly slow-twitch), the medial head of the gastrocnemius (superficial fast-twitch and deep mixed-fiber regions), and the plantaris (predominantly fast-twitch).
ResultsHeart failure rats exhibited pulmonary congestion at 1 week, followed by progressive right ventricular hypertrophy from 2 to 4 weeks. Overt declines in exercise tolerance and a downward trend in grip strength became apparent at 4 weeks. Notably, reductions in the capillary-to-fiber ratio were detected in the deep gastrocnemius and plantaris as early as 1 week, and in the superficial gastrocnemius at 2 weeks. In contrast, muscle fiber atrophy in these muscles generally manifested later (at 2 or 4 weeks). In the soleus, both capillary loss and fiber atrophy were delayed until 4 weeks.
ConclusionMicrocirculatory disturbances and subsequent fiber atrophy, particularly in fast-twitch-dominant muscles, precede functional impairments, such as reduced grip strength and exercise intolerance. Early comprehensive management before functional deficits become apparent may be necessary to mitigate heart failure-associated skeletal muscle impairment.