Heart failure affects mitochondrial but not myofibrillar intrinsic properties of skeletal muscle

Background-Congestive heart failure (CHF) induces abnormalities in skeletal muscle that are thought to in part explain exercise intolerance. The aim o f the present study was to determine whether these changes actually result in contractile or metabolic functional alterations and whether they are mus cle type specific. Methods and Results-With a rat model of CHF (induced by aortic banding), we studied mitochondrial function, mechanical properties, and creatine kinase (CK) compartmentation in situ in permeabilized fibers from soleus (SOL), a n oxidative slow-twitch muscle, and white gastrocnemius (GAS), a glycolytic fast-twitch muscle. Animals were studied 7 months after surgery, and CHF w as documented on the basis of anatomic data. Alterations in skeletal muscle phenotype were documented with an increased proportion of fast-type fiber and fast myosin heavy chain, decreased capillary-to-fiber ratio, and decrea sed citrate synthase activity. Despite a slow-to-fast phenotype transition in SOL, no change was observed in contractile capacity or calcium sensitivi ty. However, muscles from CHF rats exhibited a dramatic decrease in oxidati ve capacities (oxygen consumption per gram of fiber dry weight) of 35% for SOL and 45% for GAS (P<0.001). Moreover, the regulation of respiration with ADP and mitochondrial CK and adenylate kinase was impaired in C-HF SOL, Mi tochondrial CK activity and content (Western blots) were dramatically decre ased in both muscles. Conclusions-CHF results in alterations in both mitochondrial function and p hosphotransfer systems but unchanged myofibrillar function in skeletal musc les, which suggests a myopathy of metabolic origin in CHF.