Vescovo G, Ceconi C, Bernocchi P, Ferrari R, Carraro U, Ambrosio G B, Libera L D
First Division of Internal Medicine, Venice City Hospital, Italy.
Cardiovasc Res. 1998 Jul;39(1):233-41. doi: 10.1016/s0008-6363(98)00041-8.
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.
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.
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 micropheres.
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).
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.
在充血性心力衰竭（CHF）中，下肢骨骼肌会出现一种肌病，其特征为萎缩以及从慢肌纤维向快肌纤维转变。导致这些变化的机制尚不清楚。
我们研究了血流和肌肉萎缩程度对右心室肥大和衰竭大鼠比目鱼肌和趾长伸肌（EDL）肌球蛋白重链（MHC）组成的影响。
通过注射30mg/kg的野百合碱在16只大鼠中诱导出CHF。8只动物注射相同剂量的野百合碱，但导致代偿性右心室肥大。还研究了两组年龄和饮食匹配的对照动物（分别为9只和5只）。通过电泳分离后的光密度扫描测定MHC1（慢亚型）、MHC2a（快氧化型）和MHC2b（快糖酵解型）的相对百分比。比目鱼肌和EDL的相对重量（肌肉重量/体重）作为肌肉萎缩的指标。通过注射荧光微球测量骨骼肌血流。
CHF大鼠和对照（Con）大鼠的比目鱼肌（0.40±0.06对0.44±0.06，p=无显著性差异）和EDL（0.47±0.04对0.45±0.02，p=0.09）萎缩程度相似。在CHF大鼠中，这两块肌肉显示出MHCs向快肌型同工酶的统计学显著重新分布。实际上，在CHF大鼠的EDL中，MHC2a为30.5±6.1%，而Con为35.8±8.6%（p<0.05）。然而，MHC2b更高（68.5±6.6%对61.0±9.6%，p=0.017）。在CHF大鼠的比目鱼肌中，MHC1减少（87.6±3.4%对91.9±5.2%，p=0.02），而MHC2a增加（12.04±3.5%对7.9±5.2%；p=0.028）。在代偿性肥大动物的肌肉中未发现类似变化。在CHF动物中，未发现MHC模式与相对肌肉重量之间的相关性。CHF大鼠的比目鱼肌血流显著低于Con（0.11±0.03ml/min/g对0.22±0.03，p<0.05），而EDL中未发现差异（0.06±0.02ml/min/g对0.08±0.02，p=无显著性差异）。
在CHF大鼠中，会出现以MHCs向快肌型同工型转变为特征的骨骼肌肌病。这种转变的幅度既与萎缩程度无关，也与骨骼肌血流无关，表明这两个因素在肌病的发病机制中不发挥关键作用。
