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(Circulation. 2000;102:1847.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Heart Failure Affects Mitochondrial but Not Myofibrillar Intrinsic Properties of Skeletal Muscle

E. De Sousa, BS; V. Veksler, MD, PhD; X. Bigard, MD, PhD; P. Mateo, BIng; R. Ventura-Clapier, PhD

From the Cardiologie Cellulaire et Moléculaire U-446 INSERM (E. De S., V.V., P.M., R.V.-C.), Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France; and Unité de Bioénergétique (X.B.), CRSSA, La Tronche Cedex, France.

Correspondence to Elvira De Sousa, U-446 INSERM, Faculté de Pharmacie, 92 296 Châtenay-Malabry, France. E-mail Elvira.desousa{at}cep.u-psud.fr

Background—Congestive heart failure (CHF) induces abnormalities in skeletal muscle that are thought to in part explain exercise intolerance. The aim of the present study was to determine whether these changes actually result in contractile or metabolic functional alterations and whether they are muscle 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), an oxidative slow-twitch muscle, and white gastrocnemius (GAS), a glycolytic fast-twitch muscle. Animals were studied 7 months after surgery, and CHF was 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 decreased citrate synthase activity. Despite a slow-to-fast phenotype transition in SOL, no change was observed in contractile capacity or calcium sensitivity. However, muscles from CHF rats exhibited a dramatic decrease in oxidative 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 CHF SOL. Mitochondrial CK activity and content (Western blots) were dramatically decreased in both muscles.

Conclusions—CHF results in alterations in both mitochondrial function and phosphotransfer systems but unchanged myofibrillar function in skeletal muscles, which suggests a myopathy of metabolic origin in CHF.

Key Words: heart failure • muscle • metabolism • mitochondria • creatine kinase

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