Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure

Luciano Dalla Libera, Barbara Ravara, Maurizio Volterrani, Valerio Gobbo, Mila Della Barbera, Annalisa Angelini, Daniela Danieli Betto, Elena Germinario, Giorgio Vescovo

Research output: Contribution to journalArticlepeer-review

Abstract

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-α (TNF-α) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg·kg-1· day-1 and 1.0 mg·kg-1·day-1) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-α and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-α and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume286
Issue number1 55-1
Publication statusPublished - Jan 2004

Keywords

  • Apoptosis
  • Cytokines
  • Myosin heavy chains

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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