(Circulation. 2000;102:1847.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Heart Failure Affects Mitochondrial but Not Myofibrillar Intrinsic Properties of Skeletal Muscle
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
This article has been cited by other articles:
 |
|
 |
|
  R. B. Nunes, M. Tonetto, N. Machado, M. Chazan, T. G. Heck, A. B. G. Veiga, and P. Dall'Ago Physical exercise improves plasmatic levels of IL-10, left ventricular end-diastolic pressure, and muscle lipid peroxidation in chronic heart failure rats J Appl Physiol, June 1, 2008; 104(6): 1641 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Li, R. E. Waters, S. I. Redfern, M. Zhang, L. Mao, B. H. Annex, and Z. Yan Oxidative Phenotype Protects Myofibers from Pathological Insults Induced by Chronic Heart Failure in Mice Am. J. Pathol., February 1, 2007; 170(2): 599 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, B. Mettauer, and X. Bigard Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure Cardiovasc Res, January 1, 2007; 73(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zoll, L. Monassier, A. Garnier, B. N'Guessan, B. Mettauer, V. Veksler, F. Piquard, R. Ventura-Clapier, and B. Geny ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction J Appl Physiol, August 1, 2006; 101(2): 385 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kinugawa, Z. Wang, P. M. Kaminski, M. S. Wolin, J. G. Edwards, G. Kaley, and T. H. Hintze Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene-Knockout Mice: Roles of Superoxide Anion and Nitric Oxide Circulation, March 29, 2005; 111(12): 1480 - 1486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garnier, D. Fortin, J. Zoll, B. N'Guessan, B. Mettauer, E. Lampert, V. Veksler, and R. Ventura-Clapier Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle FASEB J, January 1, 2005; 19(1): 43 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Momken, P. Lechene, R. Ventura-Clapier, and V. Veksler Voluntary physical activity alterations in endothelial nitric oxide synthase knockout mice Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H914 - H920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dalla Libera, B. Ravara, M. Volterrani, V. Gobbo, M. Della Barbera, A. Angelini, D. D. Betto, E. Germinario, and G. Vescovo Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure Am J Physiol Cell Physiol, January 1, 2004; 286(1): C138 - C144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Lee, J. S. Gounarides, E. S. Roos, and M. S. Wolin Influence of peroxynitrite on energy metabolism and cardiac function in a rat ischemia-reperfusion model Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1385 - H1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Garnier, D Fortin, C Delomenie, I Momken, V Veksler, and R Ventura-Clapier Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles J. Physiol., September 1, 2003; 551(2): 491 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Persinger, Y. Janssen-Heininger, S. S. Wing, D. E. Matthews, M. M. LeWinter, and M. J. Toth Effect of heart failure on the regulation of skeletal muscle protein synthesis, breakdown, and apoptosis Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E1001 - E1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ribera, B. N'Guessan, J. Zoll, D. Fortin, B. Serrurier, B. Mettauer, X. Bigard, R. Ventura-Clapier, and E. Lampert Mitochondrial Electron Transport Chain Function Is Enhanced in Inspiratory Muscles of Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 873 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Sousa, P. Lechene, D. Fortin, B. N'Guessan, S. Belmadani, X. Bigard, V. Veksler, and R. Ventura-Clapier Cardiac and skeletal muscle energy metabolism in heart failure: beneficial effects of voluntary activity Cardiovasc Res, November 1, 2002; 56(2): 260 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, E. De Sousa, and V. Veksler Metabolic Myopathy in Heart Failure Physiology, October 1, 2002; 17(5): 191 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hambrecht, P. C. Schulze, S. Gielen, A. Linke, S. Mobius-Winkler, J. Yu, J.u. Kratzsch, G. Baldauf, M. W. Busse, A. Schubert, et al. Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure J. Am. Coll. Cardiol., April 3, 2002; 39(7): 1175 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Mettauer, J. Zoll, H. Sanchez, E. Lampert, F. Ribera, V. Veksler, X. Bigard, P. Mateo, E. Epailly, J. Lonsdorfer, et al. Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects J. Am. Coll. Cardiol., October 1, 2001; 38(4): 947 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsutsui, T. Ide, S. Hayashidani, N. Suematsu, T. Shiomi, J. Wen, K.-i. Nakamura, K. Ichikawa, H. Utsumi, and A. Takeshita Enhanced Generation of Reactive Oxygen Species in the Limb Skeletal Muscles From a Murine Infarct Model of Heart Failure Circulation, July 10, 2001; 104(2): 134 - 136. [Abstract] [Full Text] [PDF]
|
|