Journal Article

Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy

Giorgio Vescovo, Claudio Ceconi, Palmira Bernocchi, Roberto Ferrari, Ugo Carraro, Giovanni Battista Ambrosio and Luciano Dalla Libera

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 39, issue 1, pages 233-241
Published in print July 1998 | ISSN: 0008-6363
Published online July 1998 | e-ISSN: 1755-3245 | DOI:

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Background: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy characterised by atrophy and shift from the slow to the fast type fibres. The mechanisms responsible for these changes are not clear yet. Objectives: We investigated the influence of blood flow and degree of muscle atrophy on the myosin heavy chains (MHC) composition of the soleus and extensor digitorum longus (EDL) of rats with right ventricle hypertrophy and failure. Methods: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight animals had the same dose of monocrotaline but resulting in compensated right ventricle hypertrophy. Two age- and diet-matched groups of control animals (nine and five respectively) were also studied. The relative percentage of MHC1 (slow isoform), MHC2a (fast oxidative) and MHC2b (fast glycolytic) was determined by densitometric scan after electrophoretic separation. The relative weights of soleus and EDL (muscle weight/body weight) were taken as an index of muscle atrophy. Skeletal muscle blood flow was measured by injecting fluorescent microspheres. Results: CHF and Control (Con) rats showed similar degree of atrophy both in soleus (0.40±0.06 vs. 0.44±0.06 p=NS), and EDL (0.47±0.04 vs. 0.45±0.02, p=0.09). In CHF rats these two muscles showed a statistically significant MHCs redistribution toward the fast type isozymes. In fact in EDL of CHF rats MHC2a was 30.5±6.1% vs. 35.8±8.6% of the Con (p<0.05). MHC2b was however higher (68.5±6.6% vs. 61.0±9.6%, p=0.017). In the soleus of CHF rats MHC1 was decreased (87.6±3.4% vs. 91.9±5.2%, p=0.02), while MHC2a was increased (12.04±3.5% vs. 7.9±5.2%; p=0.028). Similar changes were not found in the muscles of the compensated hypertrophy animals. No correlation was found between MHC pattern and the relative muscle weight in the CHF animals. Soleus blood flow in CHF rats was significantly lower than that of Con (0.11±0.03 ml/min/g vs. 0.22±0.03 p<0.05), while no differences were found in EDL (0.06±0.02 ml/min/g vs. 0.08±0.02, p=NS). Conclusions: In rats with CHF a skeletal muscle myopathy characterised by a shift of the MHCs toward the fast type isoforms occurs. The magnitude of the shift correlates neither with the degree of atrophy, nor with the skeletal muscle blood flow, suggesting that these two factors do not play a pivotal role in the pathogenesis of the myopathy.

Keywords: Heart failure; Myosin heavy chains; Skeletal muscle; Monocrotaline

Journal Article.  4944 words.  Illustrated.

Subjects: Cardiovascular Medicine