Contraction and intracellular Ca2+ handling in isolated skeletal muscle ofrats with congestive heart failure

A decreased exercise tolerance is a common symptom in patients with congest ive heart failure (CHF). This decrease has been suggested to be partly due to altered skeletal muscle function. Therefore, we have studied contractile function and cytoplasmic free Ca2+ concentration ([Ca2+](i), measured with the fluorescent dye indo 1) in isolated muscles from rats in which CHF was induced by ligation of the left coronary artery. The results show no major changes of the contractile function and [Ca2+](i) handling in unfatigued i ntact fast-twitch fibers isolated from flexor digitorum brevis muscles of C HF rats, but. these fibers were markedly more susceptible to damage during microdissection. Furthermore, CHF fibers displayed a marked increase of bas eline [Ca2+](i) during fatigue. Isolated slow-twitch soleus muscles of CHF rats displayed slower twitch contraction and tetanic relaxation than did mu scles from sham-operated rats; the slowing of relaxation became more pronou nced during fatigue in CHF muscles. Immunoblot analyses of sarcoplasmic ret iculum proteins and sarcolemma Na+,K+-ATPase showed no difference in flexor digitorum brevis muscles of sham-operated versus CHF rats. In conclusion, functional impairments can be observed in limb muscle isolated from rats wi th CHF. These impairments seem to mainly involve structures surrounding the muscle cells and sarcoplasmic reticulum Ca2+ pumps, the dysfunction of whi ch becomes obvious during fatigue.