Skip to main content
NCBI home page
Heart logoLink to Heart
. 1997 Aug;78(2):177–181. doi: 10.1136/hrt.78.2.177

Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy.

C H Thompson 1, G J Kemp 1, D J Taylor 1, M Conway 1, B Rajagopalan 1, A O'Donoghue 1, P Styles 1, W J McKenna 1, G K Radda 1
PMCID: PMC484900  PMID: 9326994

Abstract

OBJECTIVE: To determine the skeletal muscle metabolic manifestations of familial hypertrophic cardiomyopathy. DESIGN: A case-control study. SETTING: 31P magnetic resonance spectroscopy of the calf muscle was performed on volunteers from a centre specialising in familial hypertrophic cardiomyopathy. PATIENTS: Five patients with abnormal beta myosin heavy chain protein in cardiac and skeletal muscle and five patients with a troponin T abnormality in cardiac muscle were compared with healthy controls. RESULTS: High energy phosphate metabolism in vivo was examined in a non-invasive manner. In resting muscle, the beta myosin heavy chain group had a higher ratio of phosphocreatine to ATP concentration (4.51 (SD 0.17)) than either the troponin T group (3.88 (0.42)) or controls (n = 16; 4.04 (0.40)). Exercise duration was reduced compared to controls, and during the fourth minute of exercise phosphocreatine depletion and muscle acidification were greater in both patient groups. After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes). CONCLUSIONS: Exercise metabolism was abnormal in both groups of subjects, and the affected contractile protein determined the metabolic changes in muscle at rest and during recovery. In patients with abnormal beta myosin heavy chain protein, there was a decrease in oxidative capacity consistent with the reduction in mitochondria reported in muscle biopsy studies of similar patients.

Full text

PDF
177

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anan R., Greve G., Thierfelder L., Watkins H., McKenna W. J., Solomon S., Vecchio C., Shono H., Nakao S., Tanaka H. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest. 1994 Jan;93(1):280–285. doi: 10.1172/JCI116957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnold D. L., Matthews P. M., Radda G. K. Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn Reson Med. 1984 Sep;1(3):307–315. doi: 10.1002/mrm.1910010303. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. R., Taylor D. J., Kemp G. J., Radda G. K. Skeletal muscle bioenergetics in the chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1993 Jun;56(6):679–683. doi: 10.1136/jnnp.56.6.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cuda G., Fananapazir L., Zhu W. S., Sellers J. R., Epstein N. D. Skeletal muscle expression and abnormal function of beta-myosin in hypertrophic cardiomyopathy. J Clin Invest. 1993 Jun;91(6):2861–2865. doi: 10.1172/JCI116530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fananapazir L., Dalakas M. C., Cyran F., Cohn G., Epstein N. D. Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3993–3997. doi: 10.1073/pnas.90.9.3993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kemp G. J., Taylor D. J., Thompson C. H., Hands L. J., Rajagopalan B., Styles P., Radda G. K. Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise. NMR Biomed. 1993 Sep-Oct;6(5):302–310. doi: 10.1002/nbm.1940060504. [DOI] [PubMed] [Google Scholar]
  7. Lankford E. B., Epstein N. D., Fananapazir L., Sweeney H. L. Abnormal contractile properties of muscle fibers expressing beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. J Clin Invest. 1995 Mar;95(3):1409–1414. doi: 10.1172/JCI117795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lenfant C. NHLBI funding policies. Enhancing stability, predictability, and cost control. Circulation. 1994 Jul;90(1):1–1. doi: 10.1161/01.cir.90.1.1. [DOI] [PubMed] [Google Scholar]
  9. Maron B. J., Bonow R. O., Cannon R. O., 3rd, Leon M. B., Epstein S. E. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med. 1987 Mar 26;316(13):780–789. doi: 10.1056/NEJM198703263161305. [DOI] [PubMed] [Google Scholar]
  10. Meyer R. A., Brown T. R., Kushmerick M. J. Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. Am J Physiol. 1985 Mar;248(3 Pt 1):C279–C287. doi: 10.1152/ajpcell.1985.248.3.C279. [DOI] [PubMed] [Google Scholar]
  11. Smith E. R., Heffernan L. P., Sangalang V. E., Vaughan L. M., Flemington C. S. Voluntary muscle involvement in hypertrophic cardiomyopathy. A study of eleven patients. Ann Intern Med. 1976 Nov;85(5):566–572. doi: 10.7326/0003-4819-85-5-566. [DOI] [PubMed] [Google Scholar]
  12. Spirito P., Maron B. J., Bonow R. O., Epstein S. E. Severe functional limitation in patients with hypertrophic cardiomyopathy and only mild localized left ventricular hypertrophy. J Am Coll Cardiol. 1986 Sep;8(3):537–544. doi: 10.1016/s0735-1097(86)80180-2. [DOI] [PubMed] [Google Scholar]
  13. St John Sutton M. G., Lie J. T., Anderson K. R., O'Brien P. C., Frye R. L. Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis. Br Heart J. 1980 Oct;44(4):433–443. doi: 10.1136/hrt.44.4.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Vandenborne K., Walter G., Ploutz-Snyder L., Staron R., Fry A., De Meirleir K., Dudley G. A., Leigh J. S. Energy-rich phosphates in slow and fast human skeletal muscle. Am J Physiol. 1995 Apr;268(4 Pt 1):C869–C876. doi: 10.1152/ajpcell.1995.268.4.C869. [DOI] [PubMed] [Google Scholar]
  15. Watkins H., McKenna W. J., Thierfelder L., Suk H. J., Anan R., O'Donoghue A., Spirito P., Matsumori A., Moravec C. S., Seidman J. G. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995 Apr 20;332(16):1058–1064. doi: 10.1056/NEJM199504203321603. [DOI] [PubMed] [Google Scholar]
  16. Watkins H., Rosenzweig A., Hwang D. S., Levi T., McKenna W., Seidman C. E., Seidman J. G. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992 Apr 23;326(17):1108–1114. doi: 10.1056/NEJM199204233261703. [DOI] [PubMed] [Google Scholar]

Articles from Heart are provided here courtesy of BMJ Publishing Group

RESOURCES