Lunde Per Kristian, Sejersted Ole M, Thorud Hanne-Mari Schiøtz, Tønnessen Theis, Henriksen Unni Lie, Christensen Geir, Westerblad Håkan, Bruton Joseph
Institute for Experimental Medical Research, Ullevål University Hospital, N-0407 Oslo, Norway.
Circ Res. 2006 Jun 23;98(12):1514-9. doi: 10.1161/01.RES.0000226529.66545.e5. Epub 2006 May 11.
Skeletal muscle weakness and decreased exercise capacity are major symptoms reported by patients with congestive heart failure (CHF). Intriguingly, these skeletal muscle symptoms do not correlate with the decreased heart function. This suggests that CHF leads to maladaptive changes in skeletal muscles, and as reported most markedly in slow-twitch muscles. We used rats at 6 weeks after infarction to measure expression of key proteins involved in SR Ca(2+) release and uptake in slow-twitch soleus muscles. We also measured force and myoplasmic free [Ca(2+)] (Ca(2+)) in intact single fibers of soleus muscles. CHF rats showed clear signs of severe cardiac dysfunction with marked increases in heart weight and left ventricular end-diastolic pressure compared with sham operated rats (Sham). There were small, but significant, changes in the content of proteins involved in cellular Ca(2+) handling in CHF muscles: slight increases in SR Ca(2+) release channels (ie, the ryanodine receptors) and in SR Ca(2+)-ATPase. Tetanic force and Ca(2+) were not significantly different between CHF and Sham soleus fibers under resting conditions. However, during the stimulation period there was a decrease in tetanic force without changes in Ca(2+) in CHF fibers that was not observed in Sham fibers. The fatigue-induced changes recovered rapidly. We conclude that CHF soleus fibers fatigue more rapidly than Sham fibers because of a reversible fatigue-induced decrease in myofibrillar function.
骨骼肌无力和运动能力下降是充血性心力衰竭（CHF）患者报告的主要症状。有趣的是，这些骨骼肌症状与心脏功能下降并无关联。这表明CHF会导致骨骼肌发生适应性不良变化，且在慢肌纤维中表现最为明显。我们使用梗死后6周的大鼠来测量慢肌比目鱼肌中参与肌浆网Ca(2+)释放和摄取的关键蛋白的表达。我们还测量了比目鱼肌完整单纤维中的肌力和肌浆游离[Ca(2+)]（Ca(2+)）。与假手术大鼠（Sham）相比，CHF大鼠表现出严重心脏功能障碍的明显迹象，心脏重量和左心室舒张末期压力显著增加。CHF肌肉中参与细胞Ca(2+)处理的蛋白质含量有微小但显著的变化：肌浆网Ca(2+)释放通道（即兰尼碱受体）和肌浆网Ca(2+)-ATP酶略有增加。在静息状态下，CHF和Sham比目鱼肌纤维的强直收缩力和Ca(2+)并无显著差异。然而，在刺激期，CHF纤维的强直收缩力下降，而Ca(2+)没有变化，这在Sham纤维中未观察到。疲劳诱导的变化迅速恢复。我们得出结论，由于疲劳诱导的肌原纤维功能可逆性下降，CHF比目鱼肌纤维比Sham纤维更容易疲劳。
