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Circulation, Vol 81, 518-527, Copyright © 1990 by American Heart Association
MJ Sullivan, HJ Green and FR Cobb
Recent studies in patients with long-term heart failure have suggested that
intrinsic abnormalities in skeletal muscle can contribute to the
development of early lactic acidosis and fatigue during exercise. The
present study provides an analysis of substrate and enzyme content, fiber
typing, and capillarization in skeletal muscle biopsy samples obtained at
rest from the vastus lateralis in 11 patients with long- term heart failure
(left ventricular ejection fraction, 21 +/- 8%) and nine normal subjects.
Patients demonstrated a reduced peak exercise oxygen consumption (13.0 +/-
3.3 ml/kg/min) when compared with normals (30.2 +/- 8.6 ml/kg/min, p less
than 0.001) and had an accelerated rise in blood lactate levels during
exercise. In mixed fiber skeletal muscle, total phosphorylase and
glycolytic enzyme activities were not different in the two groups, whereas
mitochondrial enzymes involved in terminal oxidation were decreased in
patients as compared with normal subjects as indicated by reductions in
succinate dehydrogenase (51 +/- 15 vs. 81 +/- 17 microM/g protein/min, p
less than 0.001) and citrate synthetase (26 +/- 7 vs. 43 +/- 20 microM/g
protein/min, p less than 0.05). 3-Hydroxyacyl-CoA-dehydrogenase, an
important enzyme mediating beta-oxidation of fatty acids, was also reduced
in patients as compared with normals (18 +/- 7 vs. 27 +/- 10 microM/g
protein/min, p less than 0.05). There was no difference in high-energy
phosphagens or lactate concentration of mixed muscle in the two groups,
whereas glycogen content was decreased in patients (262 +/- 29 vs. 298 +/-
35 microM glucosyl units/kg dry wt, p = 0.01). Patients demonstrated a
reduced percentage of slow twitch type I fibers (36 +/- 7% vs. 52 +/- 22%,
p less than 0.05) and had a higher percentage of type IIb fast twitch
fibers (24 +/- 9% vs. 11 +/- 12%, p = 0.02), which were smaller than the
type IIb fibers seen in normal subjects (p less than 0.05). In patients,
the number of capillaries per fiber was decreased for type I and type IIa
fibers (both, p less than 0.03), but the ratio of capillaries to
cross-sectional fiber area was not different for the two groups. These data
demonstrate major alterations in skeletal muscle histology and biochemistry
in patients with long-term heart failure, including fiber atrophy, a
decrease in percentage of composition of type I fibers, and an increase in
type IIb fibers accompanied by a decrease in oxidative enzyme
capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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V. Adams, H. Jiang, J. Yu, S. Mobius-Winkler, E. Fiehn, A. Linke, C. Weigl, G. Schuler, and R. Hambrecht Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance J. Am. Coll. Cardiol., March 15, 1999; 33(4): 959 - 965. [Abstract] [Full Text] [PDF]
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R. Hambrecht, V. Adams, S. Gielen, A. Linke, S. Mobius-Winkler, J. Yu, J. Niebauer, H. Jiang, E. Fiehn, and G. Schuler Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle J. Am. Coll. Cardiol., January 1, 1999; 33(1): 174 - 179. [Abstract] [Full Text] [PDF]
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J. K. Shoemaker, A. R. Kunselman, D. H. Silber, and L. I. Sinoway Maintained exercise pressor response in heart failure J Appl Physiol, November 1, 1998; 85(5): 1793 - 1799. [Abstract] [Full Text] [PDF]
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G. Vescovo, L. Dalla Libera, F. Serafini, C. Leprotti, L. Facchin, M. Volterrani, C. Ceconi, and G. B. Ambrosio Improved Exercise Tolerance After Losartan and Enalapril in Heart Failure : Correlation With Changes in Skeletal Muscle Myosin Heavy Chain Composition Circulation, October 27, 1998; 98(17): 1742 - 1749. [Abstract] [Full Text] [PDF]
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G. Vescovo, C. Ceconi, P. Bernocchi, R. Ferrari, U. Carraro, G. B. Ambrosio, and L. Dalla Libera Skeletal muscle myosin heavy chain expression in rats with monocrotaline-induced cardiac hypertrophy and failure. Relation to blood flow and degree of muscle atrophy Cardiovasc Res, July 1, 1998; 39(1): 233 - 241. [Abstract] [Full Text] [PDF]
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D. H. Silber, G. Sutliff, Q. X. Yang, M. B. Smith, L. I. Sinoway, and U. A. Leuenberger Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure J Appl Physiol, May 1, 1998; 84(5): 1551 - 1559. [Abstract] [Full Text] [PDF]
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D. G. Peters, H. L. Mitchell, S. A. McCune, S. Park, J. H. Williams, and S. C. Kandarian Skeletal Muscle Sarcoplasmic Reticulum Ca2+-ATPase Gene Expression in Congestive Heart Failure Circ. Res., November 19, 1997; 81(5): 703 - 710. [Abstract] [Full Text]
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M. D. Delp, C. Duan, J. P. Mattson, and T. I. Musch Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure J Appl Physiol, October 1, 1997; 83(4): 1291 - 1299. [Abstract] [Full Text] [PDF]
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B. Tikunov, S. Levine, and D. Mancini Chronic Congestive Heart Failure Elicits Adaptations of Endurance Exercise in Diaphragmatic Muscle Circulation, February 18, 1997; 95(4): 910 - 916. [Abstract] [Full Text]
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C. C. Lang, D. B. Chomsky, G. Rayos, T. K. Yeoh, and J. R. Wilson Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure J Appl Physiol, January 1, 1997; 82(1): 257 - 261. [Abstract] [Full Text] [PDF]
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D. Mancini, S. Katz, L. Donchez, and K. Aaronson Coupling of Hemodynamic Measurements With Oxygen Consumption During Exercise Does Not Improve Risk Stratification in Patients With Heart Failure Circulation, November 15, 1996; 94(10): 2492 - 2496. [Abstract] [Full Text]
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J. R. Wilson, J. Groves, and G. Rayos Circulatory Status and Response to Cardiac Rehabilitation in Patients With Heart Failure Circulation, October 1, 1996; 94(7): 1567 - 1572. [Abstract] [Full Text]
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M. Piepoli, A. L. Clark, M. Volterrani, S. Adamopoulos, P. Sleight, and A. J.S. Coats Contribution of Muscle Afferents to the Hemodynamic, Autonomic, and Ventilatory Responses to Exercise in Patients With Chronic Heart Failure : Effects of Physical Training Circulation, March 1, 1996; 93(5): 940 - 952. [Abstract] [Full Text]
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D. M. Mancini, D. Henson, J. L. Manca, L. Donchez, and S. Levine Benefit of Selective Respiratory Muscle Training on Exercise Capacity in Patients With Chronic Congestive Heart Failure Circulation, January 15, 1995; 91(2): 320 - 329. [Abstract] [Full Text]
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J. R. Wilson Exercise Intolerance in Heart Failure : Importance of Skeletal Muscle Circulation, January 15, 1995; 91(2): 559 - 561. [Full Text]
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