Apoptosis in the Skeletal Muscle of Rats with Heart Failure is Associated with Increased Serum Levels of TNF-α and Sphingosine

Skeletal muscle in congestive heart failure (CHF) is responsible for increased fatigability, decreased endurance and exercise capacity. A specific myopathy with increased expression of fast myosin heavy chains (MHCs), myocyte atrophy, secondary to myocyte apoptosis, that is triggered by high levels of circulating tumor necrosis factor (TNF- α) has been described. However, a direct effect of TNF- α on skeletal muscle has not been described yet. In this paper we put forward the hypothesis that TNF- α plays an indirect effect on skeletal myocytes. In an animal model of CHF, the monocrotaline-treated rat, we have observed a significant (P