Effects of Congestive Heart Failure on Ca2 Handling in Skeletal Muscle During Fatigue

Abstract—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 Ca2 release and uptake in slow-twitch soleus muscles. We also measured force and myoplasmic free [Ca2] ([Ca2]i) 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 Ca2 handling in CHF muscles: slight increases in SR Ca2 release channels (ie, the ryanodine receptors) and in SR Ca2-ATPase. Tetanic force and [Ca2]i 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 [Ca2]i 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. (Circ Res. 2006;98:1514-1519.) Key Words: skeletal muscle congestive heart failure muscle fatigue Ca2 Patients with congestive heart failure (CHF) frequentlyreport skeletal muscle weakness and decreased fatigu