SKELETAL-MUSCLE MYOSIN HEAVY-CHAIN EXPRESSION IN RATS WITH MONOCROTALINE-INDUCED CARDIAC-HYPERTROPHY AND FAILURE - RELATION TO BLOOD-FLOW AND DEGREE OF MUSCLE ATROPHY

Background: In congestive heart failure (CHF) the skeletal muscle of t he 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 influ ence of blood flow and degree of muscle atrophy on the myosin heavy ch ains (MHC) composition of the soleus and extensor digitorum longus (ED L) of rats with right ventricle hypertrophy and failure. Methods: CHF was induced in 16 rats by injecting 30 mg/kg monocrotaline. Eight anim als had the same dose of monocrotaline but resulting in compensated ri ght 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 (f ast glycolytic) was determined by densitometric scan after electrophor etic separation. The relative weights of soleus and EDL (muscle weight /body weight) were taken as an index of muscle atrophy. Skeletal muscl e blood flow was measured by injecting fluorescent microspheres. Resul ts: CHF and Control (Con) rats showed similar degree of atrophy both i n 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 stati stically 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% v s. 7.9+/-5.2%; p = 0.028). Similar changes were not found in the muscl es of the compensated hypertrophy animals. No correlation was found be tween MHC pattern and the relative muscle weight in the CHF animals. S oleus 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). Conclu sions: 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 t he skeletal muscle blood flow, suggesting that these two factors do no t play a pivotal role in the pathogenesis of the myopathy. (C) 1998 El sevier Science BN. All rights reserved.