Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Dec;88(6):2047–2053. doi: 10.1172/JCI115533

Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

W H Martin 3rd 1, R J Spina 1, E Korte 1, K E Yarasheski 1, T J Angelopoulos 1, P M Nemeth 1, J E Saffitz 1
PMCID: PMC295798  PMID: 1752962

Abstract

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.

Full text

PDF
2047

Selected References

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

  1. Armstrong R. B., Phelps R. O. Muscle fiber type composition of the rat hindlimb. Am J Anat. 1984 Nov;171(3):259–272. doi: 10.1002/aja.1001710303. [DOI] [PubMed] [Google Scholar]
  2. Cavallo A., Casta A., Fawcett H. D., Nusynowitz M. L., Wolf W. J. Is there a thyrotoxic cardiomyopathy in children? J Pediatr. 1985 Oct;107(4):531–536. doi: 10.1016/s0022-3476(85)80010-x. [DOI] [PubMed] [Google Scholar]
  3. Chi M. M., Hintz C. S., Coyle E. F., Martin W. H., 3rd, Ivy J. L., Nemeth P. M., Holloszy J. O., Lowry O. H. Effects of detraining on enzymes of energy metabolism in individual human muscle fibers. Am J Physiol. 1983 Mar;244(3):C276–C287. doi: 10.1152/ajpcell.1983.244.3.C276. [DOI] [PubMed] [Google Scholar]
  4. Coyle E. F., Martin W. H., 3rd, Bloomfield S. A., Lowry O. H., Holloszy J. O. Effects of detraining on responses to submaximal exercise. J Appl Physiol (1985) 1985 Sep;59(3):853–859. doi: 10.1152/jappl.1985.59.3.853. [DOI] [PubMed] [Google Scholar]
  5. Evans W. J., Phinney S. D., Young V. R. Suction applied to a muscle biopsy maximizes sample size. Med Sci Sports Exerc. 1982;14(1):101–102. [PubMed] [Google Scholar]
  6. Forfar J. C., Muir A. L., Sawers S. A., Toft A. D. Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy. N Engl J Med. 1982 Nov 4;307(19):1165–1170. doi: 10.1056/NEJM198211043071901. [DOI] [PubMed] [Google Scholar]
  7. Gelfand R. A., Hutchinson-Williams K. A., Bonde A. A., Castellino P., Sherwin R. S. Catabolic effects of thyroid hormone excess: the contribution of adrenergic activity to hypermetabolism and protein breakdown. Metabolism. 1987 Jun;36(6):562–569. doi: 10.1016/0026-0495(87)90168-5. [DOI] [PubMed] [Google Scholar]
  8. Hammond H. K., White F. C., Buxton I. L., Saltzstein P., Brunton L. L., Longhurst J. C. Increased myocardial beta-receptors and adrenergic responses in hyperthyroid pigs. Am J Physiol. 1987 Feb;252(2 Pt 2):H283–H290. doi: 10.1152/ajpheart.1987.252.2.H283. [DOI] [PubMed] [Google Scholar]
  9. Iskandrian A. S., Rose L., Hakki A. H., Segal B. L., Kane S. A. Cardiac performance in thyrotoxicosis: analysis of 10 untreated patients. Am J Cardiol. 1983 Jan 15;51(2):349–352. doi: 10.1016/s0002-9149(83)80064-2. [DOI] [PubMed] [Google Scholar]
  10. MITCHELL J. H., SPROULE B. J., CHAPMAN C. B. The physiological meaning of the maximal oxygen intake test. J Clin Invest. 1958 Apr;37(4):538–547. doi: 10.1172/JCI103636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Martin W. H., 3rd, Coggan A. R., Spina R. J., Saffitz J. E. Effects of fiber type and training on beta-adrenoceptor density in human skeletal muscle. Am J Physiol. 1989 Nov;257(5 Pt 1):E736–E742. doi: 10.1152/ajpendo.1989.257.5.E736. [DOI] [PubMed] [Google Scholar]
  12. Martin W. H., 3rd, Coyle E. F., Bloomfield S. A., Ehsani A. A. Effects of physical deconditioning after intense endurance training on left ventricular dimensions and stroke volume. J Am Coll Cardiol. 1986 May;7(5):982–989. doi: 10.1016/s0735-1097(86)80215-7. [DOI] [PubMed] [Google Scholar]
  13. Martin W. H., 3rd, Montgomery J., Snell P. G., Corbett J. R., Sokolov J. J., Buckey J. C., Maloney D. A., Blomqvist C. G. Cardiovascular adaptations to intense swim training in sedentary middle-aged men and women. Circulation. 1987 Feb;75(2):323–330. doi: 10.1161/01.cir.75.2.323. [DOI] [PubMed] [Google Scholar]
  14. Martin W. H., 3rd, Murphree S. S., Saffitz J. E. Beta-adrenergic receptor distribution among muscle fiber types and resistance arterioles of white, red, and intermediate skeletal muscle. Circ Res. 1989 Jun;64(6):1096–1105. doi: 10.1161/01.res.64.6.1096. [DOI] [PubMed] [Google Scholar]
  15. Massey D. G., Becklake M. R., McKenzie J. M., Bates D. V. Circulatory and ventilatory response to exercise in thyrotoxicosis. N Engl J Med. 1967 May 18;276(20):1104–1112. doi: 10.1056/NEJM196705182762002. [DOI] [PubMed] [Google Scholar]
  16. Matthews D. E., Motil K. J., Rohrbaugh D. K., Burke J. F., Young V. R., Bier D. M. Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine. Am J Physiol. 1980 May;238(5):E473–E479. doi: 10.1152/ajpendo.1980.238.5.E473. [DOI] [PubMed] [Google Scholar]
  17. Matthews D. E., Schwarz H. P., Yang R. D., Motil K. J., Young V. R., Bier D. M. Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment. Metabolism. 1982 Nov;31(11):1105–1112. doi: 10.1016/0026-0495(82)90160-3. [DOI] [PubMed] [Google Scholar]
  18. Nolte J., Pette D., Bachmaier B., Kiefhaber P., Schneider H., Scriba P. C. Enzyme response to thyrotoxicosis and hypothyroidism in human liver and muscle: comparative aspects. Eur J Clin Invest. 1972 Mar;2(3):141–149. doi: 10.1111/j.1365-2362.1972.tb00582.x. [DOI] [PubMed] [Google Scholar]
  19. Pollack M. L., Schmidt D. H., Jackson A. S. Measurement of cardio-respiratory fitness and body composition in the clinical setting. Compr Ther. 1980 Sep;6(9):12–27. [PubMed] [Google Scholar]
  20. Sahn D. J., DeMaria A., Kisslo J., Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978 Dec;58(6):1072–1083. doi: 10.1161/01.cir.58.6.1072. [DOI] [PubMed] [Google Scholar]
  21. Schwarz H. P., Karl I. E., Bier D. M. The alpha-keto acids of branched-chain amino acids: simplified derivatization for physiological samples and complete separation as quinoxalinols by packed column gas chromatography. Anal Biochem. 1980 Nov 1;108(2):360–366. doi: 10.1016/0003-2697(80)90600-4. [DOI] [PubMed] [Google Scholar]
  22. Scrimgeour C. M., Smith K., Rennie M. J. Automated measurement of 13C enrichment in carbon dioxide derived from submicromole quantities of L-(1-13C)-leucine. Biomed Environ Mass Spectrom. 1988 Apr 1;15(7):369–374. doi: 10.1002/bms.1200150704. [DOI] [PubMed] [Google Scholar]
  23. Shafer R. B., Bianco J. A. Assessment of cardiac reserve in patients with hyperthyroidism. Chest. 1980 Aug;78(2):269–273. doi: 10.1378/chest.78.2.269. [DOI] [PubMed] [Google Scholar]
  24. Shah S. D., Clutter W. E., Cryer P. E. External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine. J Lab Clin Med. 1985 Dec;106(6):624–629. [PubMed] [Google Scholar]
  25. Sonnenblick E. H., Strobeck J. E. Current concepts in cardiology. Derived indexes of ventricular and myocardial function. N Engl J Med. 1977 Apr 28;296(17):978–982. doi: 10.1056/NEJM197704282961706. [DOI] [PubMed] [Google Scholar]
  26. TATA J. R., ERNSTER L., LINDBERG O., ARRHENIUS E., PEDERSEN S., HEDMAN R. The action of thyroid hormones at the cell level. Biochem J. 1963 Mar;86:408–428. doi: 10.1042/bj0860408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Triebwasser J. H., Johnson R. L., Burpo R. P., Campbell J. C., Reardon W. C., Blomqvist C. G. Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements. Aviat Space Environ Med. 1977 Mar;48(3):203–209. [PubMed] [Google Scholar]
  28. Victor R. G., Bertocci L. A., Pryor S. L., Nunnally R. L. Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans. J Clin Invest. 1988 Oct;82(4):1301–1305. doi: 10.1172/JCI113730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winder W. W. Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria. Am J Physiol. 1979 Mar;236(3):C132–C138. doi: 10.1152/ajpcell.1979.236.3.C132. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES