The Effects of Cardiac Hypertrophy on Intracellular Ca2+ Handling

  • James P. Morgan
  • Roderick MacKinnon
  • Marc Feldman
  • William Grossman
  • Judith Gwathmey


The development of cardiac hypertrophy is associated with marked changes in contractile function in many mammalian species [1]. In isolated ventricular muscle, these changes usually manifest themselves as alterations in force generation and in the rate of relaxation [2]. The studies described in this chapter were designed to answer the question of whether the mechanical abnormalities of hypertrophied muscle are related to changes in intracellular Ca2+ handling. Four models of hypertrophy will be considered, including (1) pressure-overload right ventricular hypertrophy in ferrets, (2) alteration of the thyroid state in ferrets, (3) the compensatory hypertrophy that occurs in patients with heart failure, and (4) hypertrophic cardiomyopathy in humans.


Sarcoplasmic Reticulum Cardiac Hypertrophy Papillary Muscle Calcium Transient Thyroid State 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alpert NR (1983). Introduction. In Alpert NR (ed): Perspectives in Cardiovascular Research, vol 7: Myocardial Hypertrophy and Failure. New York: Raven Press, pp xxi-xxxv.Google Scholar
  2. 2.
    Mirsky I, Pfeffer JM, Pfeffer MA (1983). Mechanical properties of normal and hypertrophied myocardium: Is there a relationship between diastolic and systolic function? In Alpert NR (ed): Perspectives in Cardiovascular Research, vol 7: Myocardial Hypertrophy and Failure New York: Raven Press, pp 39–55.Google Scholar
  3. 3.
    Spann JF, Buccino RA, Sonnenblick EH, Braunwald E (1967). Contractile state of cardiac muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circ Res 21: 341–354.PubMedGoogle Scholar
  4. 4.
    Spann JF, Covell JW, Eckberg DL, et al (1972). Contractile performance of the hypertrophied and chronically failing cat ventricle. Am J Physiol 223: 1150–1157.PubMedGoogle Scholar
  5. 5.
    Cooper G, Tomanek RJ, Erdhardt JC, Marcus ML (1981). Chronic progressive overload of the cat right ventricle. Circ Res 48: 488–497.PubMedGoogle Scholar
  6. 6.
    Spann JF (1983). Contractile and pump function of the pressure overloaded heart. In Alpert NR (ed): Perspectives in Cardiovascular Research, vol 7: Myocardial Hypertrophy and Failure New York: Raven Press, pp 19–33.Google Scholar
  7. 7.
    Gwathmey JK, Morgan JP (1985). Altered calcium handling in experimental pressure-over-load hypertrophy in the ferret. Circ Res 57: 836–843.PubMedGoogle Scholar
  8. 8.
    Morgan JP, Blinks JR (1982). Intracellular Ca2+ transients in the cat papillary muscle. Can J Physiol Pharmacol 60: 524–528.PubMedCrossRefGoogle Scholar
  9. 9.
    Allen DG, Blinks JR (1978). Calcium transients in aequorin injected frog cardiac muscle. Nature 273: 509–513.PubMedCrossRefGoogle Scholar
  10. 10.
    Morgan JP, Morgan KG (1984). Calcium and cardiovascular function: Intracellular calcium levels during contraction and relaxation of mammalian cardiac and vascular smooth muscle as detected with aequorin. Am J Med 77: 33–46.PubMedCrossRefGoogle Scholar
  11. 11.
    Shlafer M, Gelband H, Sung RF, et al (1978). Time-dependent alterations of myocardial microsomal yield and calcium accumulation in experimentally-induced right ventricular hypertrophy and failure. J Mol Cell Cardiol 10: 395–407.PubMedCrossRefGoogle Scholar
  12. 12.
    Sordahl LA, McCollum WB, Wood WG, Schwartz A (1978). Mitochondria and sarcoplasmic reticulum function in cardiac hypertrophy and failure. Am J Physiol 224: 497–502.Google Scholar
  13. 13.
    Malhotra A, Penpargkul S, Schaible T, Scheuer J (1981). Contractile proteins and sarcoplasmic reticulum in physiologic cardiac hypertrophy. Am J Physiol 24l: H263 - H267.Google Scholar
  14. 14.
    Scheuer J (1983). Alteration in sarcoplasmic reticulum in cardiac hypertrophy. In Tarazi RC, Dunbar JB (ed): Perspectives in Cardiovascular Research, vol 8: Cardiac Hypertrophy in Hypertension New York: Raven Press, pp 111–122.Google Scholar
  15. 15.
    Briggs NF, Wise RM, Feher JJ (1983). Diagnosis of alterations in sarcoplasmic reticulum function. In Alpert NR (ed): Perspectives in Cardiovascular Research, vol 7: Myocardial Hypertrophy and Failure New York: Raveri Press, pp 513–525.Google Scholar
  16. 16.
    Paulus WJ, Brutsaert DL (1982). Relaxation abnormalities in cardiac hypertrophy. Eur Heart J 3: 133–137.PubMedGoogle Scholar
  17. 17.
    Allen DG, Orchard CH (1983). Intracellular calcium concentrations during hypoxia and metabolic inhibition in mammalian ventricular muscle. J Physiol (Lond) 339: 107–122.Google Scholar
  18. 18.
    Housmans PR, Lee NKM, Blinks JR (1983). Active shortening retards the decline of the intracellular calcium transient in mammalian heart muscle. Science 221: 159–161.PubMedCrossRefGoogle Scholar
  19. 19.
    Buccino RA, Spann JF, Pool PE, et al (1967). Influence of the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. J Clin Invest 46: 1669–1681.PubMedCrossRefGoogle Scholar
  20. 20.
    Suko J (1971). Alterations of Ca2+ uptake and Ca2+-activated ATPase of cardiac sarcoplasmic reticulum in hyper and hypothyroidism. Bio-chim Biophys Acta 252: 324–327.CrossRefGoogle Scholar
  21. 21.
    Suko J (1973). The calcium pump of cardiac sarcoplasmic reticulum: Functional alterations at different levels of thyroid state in rabbits. J Physiol (Lond) 228: 563–582.Google Scholar
  22. 22.
    Limas CJ (1978). Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism. Am J Physiol 234: H426 - H431.PubMedGoogle Scholar
  23. 23.
    Conway G, Heazlitt RA, Fowler NO, et al (1976). The effect of hyperthyroidism on the sarcoplasmic reticulum and myosin ATPase of dogs hearts. J Mol Cell Cardiol 8: 39–51.PubMedCrossRefGoogle Scholar
  24. 24.
    Taskass IE, Szabo J, Nosztray K, et al (1985). Alterations of contractility and sarcoplasmic reticulum function of rat heart in experimental hypo-and hyperthyroidism. Gen Physiol Biophys 4: 271–278.Google Scholar
  25. 25.
    MacKinnon R, Morgan JP (1986). Influence of the thyroid state on the calcium transient in ventricular muscle. Pfluegers Arch 407: 142–144.CrossRefGoogle Scholar
  26. 26.
    Morkin E, Flink IL (1983). Biochemical and physiologic effects of thyroid hormone on cardiac performance. Prog Cardiovasc Dis 25: 435–464.PubMedCrossRefGoogle Scholar
  27. 27.
    Strauer BE, Scherpe A (1975). Experimental hyperthyroidism II: Mechanics of contraction and relaxation of isolated ventricular myocardium. Basic Res Cardiol 70: 131–141.PubMedGoogle Scholar
  28. 28.
    Barany M (1967). ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol (Suppl) 50: 196–216.Google Scholar
  29. 29.
    Pagani ED, Julian FJ (1984). Rabbit papillary muscle myosin isozymes and the velocity of muscle shortening. Circ Res 54: 586–594.PubMedGoogle Scholar
  30. 30.
    Marriott ML, McNeill JH (1983). Effect of thyroid hormone treatment on responses of the isolated working rat heart. Can J Physiol Pharmacol 61: 1382–1390.PubMedCrossRefGoogle Scholar
  31. 31.
    Solaro JR, Briggs FN (1974). Estimating the functional capabilities of sarcoplasmic reticulum in cardiac muscle. Circ Res 34: 531–540.PubMedGoogle Scholar
  32. 32.
    MacKinnon R, Allen P, Morgan JP (1986). The thyroid state influences myosin and calcium handling in ferret ventricle. Circulation 74 (suppl II): 432.Google Scholar
  33. 33.
    Feldman MD, Copelas L, Gwathmey JR, et al (1987). Pharmacologic evidence that deficient production of cyclic adenosine monophosphate may be the primary cause of contractile dysfunction in end-stage heart failure. Circulation 75: 331–339.PubMedCrossRefGoogle Scholar
  34. 34.
    Morgan JP, Chesebro JH, Pluth JR, et al (1984). Intracellular calcium transients in human working myocardium as detected with aequorin. J Am Coll Cardiol 3: 410–418.PubMedCrossRefGoogle Scholar
  35. 35.
    Grossman W, McLaurin LP, Rolett EL (1979). Alterations in left ventricular relaxation and diastolic compliance in congestive cardiomyopathy. Cardiovasc Res 13: 514–522.PubMedCrossRefGoogle Scholar
  36. 36.
    Gwathmey JK, Copelas L, Grossman W, Morgan JP (1986). Calcium handling by normal and diseased human myocardium. J Gen Physiol 1986; 88: 27a.Google Scholar
  37. 37.
    Gwathmey JK, Copelas L, MacKinnon R, et al (1987). Abnormal intracellular calcium handing in myocardium from patients with end-stage heart failure. Circ Res 61: 70–76.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing 1987

Authors and Affiliations

  • James P. Morgan
  • Roderick MacKinnon
  • Marc Feldman
  • William Grossman
  • Judith Gwathmey

There are no affiliations available

Personalised recommendations