Advertisement

Excitation-Contraction Coupling and Contractile Protein Function in Failing and Nonfailing Human Myocardium

  • Gerd Hasenfuss
  • Burkert Pieske
  • Christian Holubarsch
  • Norman R. Alpert
  • Hanjörg Just
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 346)

Abstract

Isometric force, heat output, and aequorin light emission were measured in isolated muscle strips from nonfailing human hearts and from hearts with endstage failing dilated cardiomyopathy (37°C; 30–180 beats per minute (bpm)). In nonfailing myocardium, peak twitch tension increased with higher rates of stimulation, whereas the force-frequency relation was inverse in the failing myocardium. At 60 bpm and at higher rates of stimulation, peak twitch tension was reduced significantly in the failing myocardium. Myothermal measurements, performed at 60 bpm, indicated that the number of crossbridge interactions and the amount of calcium cycling are reduced significantly in the failing myocardium. Furthermore, aequorin light transients indicated that the inverse force-frequency relation in failing myocardium results from altered calcium cycling; with increasing rates of stimulation aequorin light emission increased continuously in the nonfailing and decreased continuously in the failing myocardium. The data suggest that impaired myocardial performance in failing human myocardium may result primarily from disturbed excitation-contraction coupling processes with a reduced amount of calcium cycling and, thus, a decreased activation of contractile proteins.

Keywords

Dilate Cardiomyopathy Human Myocardium Sarcoplasmic Reticulum Calcium Calcium Cycling Intracellular Calcium Handling 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sagman WS, Kurie K, Billingham ME, Harrison DC, Stinson EB. Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N Engl J Med 1982; 307: 205–211.PubMedCrossRefGoogle Scholar
  2. 2.
    Böhm M, Gierschik P, Erdmann E. Quantification of Gia-proteins in the failing and nonfailing human myocardium. Basic Res Cardiol 1992; 87(1): 37–50.Google Scholar
  3. 3.
    Hasenfuss G, Mulieri LA, Leavitt BJ, Allen PD, Haeberle JR, Alpert NR. Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res 1992; 70: 1225–1232.PubMedCrossRefGoogle Scholar
  4. 4.
    Margossian SS, White HD, Calfield JB, Norton P, Taylor S, Slayter HS. Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function. Circulation 1992; 85: 1720–1733.PubMedCrossRefGoogle Scholar
  5. 5.
    Schultheiss H-P. Dysfunction of the ADP/ATP carrier as a causative factor for the disturbance of the myocardial energy metabolism in dilated cardiomyopathy. Basic Res Cardiol 1992; 87(1). 311–320.PubMedGoogle Scholar
  6. 6.
    Morgan JP. Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 1991; 325: 625–632.PubMedCrossRefGoogle Scholar
  7. 7.
    Beuckelmann DJ, Näbauer M, Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 1992; 85: 1046–1055.PubMedCrossRefGoogle Scholar
  8. 8.
    Mulieri LA, Hasenfuss G, Leavitt BJ, Allen PD, Alpert NR. Altered myocardial force-frequency relation in human heart failure. Circulation 1992; 85: 1743–1750.PubMedCrossRefGoogle Scholar
  9. 9.
    Pieske B, Hasenfuss G, Holubarsch Ch, Schwinger R, Böhm M, Just H. Alterations of the force-frequency relationship in the failing human heart depend on the underlying cardiac disease. Basic Res Cardiol 1992; 87(1): 213–221.PubMedGoogle Scholar
  10. 10.
    Pieske B, Kretschmann B, Holubarsch CH, Posival H, Just H, Hasenfuss G. Alteration of intracellular calcium handling causes inverse force-frequency relation in the failing human myocardium. 1993; (in preparation).Google Scholar
  11. 11.
    Mulieri LA, Leavitt BJ, Hasenfuss G, Allen PD, Alpert NR. Contractile frequency dependence of twitch and diastolic tension in dilated cardiomyopathy. Basic Res Cardiol 1992; 87(1): 199–212.PubMedGoogle Scholar
  12. 12.
    Mulieri LA, Hasenfuss G, Ittleman F, Blanchard EM, Alpert NR. Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime. Circ Res 1992; 65: 1441–1444.CrossRefGoogle Scholar
  13. 13.
    Mulieri LA, Luhr G, Trefry J, Alpert NR. Metal-film thermopiles for use with rabbit right ventricular papillary muscle. Am J Physiol 1977; 233: C146–C156.PubMedGoogle Scholar
  14. 14.
    Hasenfuss G, Mulieri LA, Blanchard EM, Holubarsch Ch, Leavitt BJ, Ittleman F, Alpert NR. Energetics of isometric force development in control and volume overload human myocardium. Comparison with animal species. Circ Res 1991; 68: 836–846.PubMedCrossRefGoogle Scholar
  15. 15.
    Alpert NR, Blanchard EM, Mulieri LA. Tension independent heat in rabbit papillary muscle. J Physiol (Lond) 1989; 414: 433–453.Google Scholar
  16. 16.
    Kuihara Y, Morgan J. A comparative study of three methods for intracellular loading of the calcium indicator aequorin in ferret papillary muscles. Biochem Biophys Res Corn 1989; 162: 402–407.CrossRefGoogle Scholar
  17. 17.
    Wang J, Morgan JP. Endocardial endothelium modulates myofilament Ca2+ responsiveness in aequorinloaded ferret myocardium. Circ Res 1992; 70: 754–760.PubMedCrossRefGoogle Scholar
  18. 18.
    Gwathmey JK, Copelas L, Mackinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 1987; 61: 70–76.PubMedCrossRefGoogle Scholar
  19. 19.
    Gwathmey JK, Slawsky MT, Hajjar RJ, Briggs GM, Morgan JP. Role of intracellular calcium handling in force interval relationship of human ventricular myocardium. J Clin Invest 1990; 85: 1599–1613.PubMedCrossRefGoogle Scholar
  20. 20.
    Rasmussen PR, Minobe W, Bristow MR. Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium. Biochemical Pharmacol 1990; 39: 691–696.CrossRefGoogle Scholar
  21. 21.
    Beuckelmann DJ, Näbauer M, Erdmann E. Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol 1991; 23: 929–937.PubMedCrossRefGoogle Scholar
  22. 22.
    Brillantes AM, Allen PD, Takahashi T, Izumo S, Marks AR. Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy. Circ Res 1992; 71: 18–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Holmberg S, Williams AJ. Single channel recordings from human cardiac sarcoplasmic reticulum. Circ Res 1989; 65: 1445–1449.PubMedCrossRefGoogle Scholar
  24. 24.
    D’Agnolo A, Luciani GB, Mazzucco A, Gallucci V, Salviati G. Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy. Circulation 1992; 85: 518–525.PubMedCrossRefGoogle Scholar
  25. 25.
    Mercadier JJ, Lompre AM, Duc P, Boheler KR, Fraysse JB, Wisnewsky C, Allen PD, Komajda M, Schwartz K. Altered sarcoplasmic reticulum Ca2+-ATPase gene expression in the human ventricle during end-stage heart failure. J Clin Invest 1990; 85: 305–309.PubMedCrossRefGoogle Scholar
  26. 26.
    Studer R, Reinecke H, Bilger J, Eschenhagen Th, Böhm M, Hasenfuss G, Just H, Holtz J, Drexler H. Gene expression of the cardiac sodium—calcium exchanger in end-stage human heart failure. J Clin Invest (submitted).Google Scholar
  27. 27.
    Takahashi T, Allen PD, Izumo S. Expression of A—, B—, and C—type natriuretic peptide genes in failing and developing human ventricles. correlation with expression of the Ca2+—ATPase gene. Circ Res 1992; 71: 9–17.PubMedCrossRefGoogle Scholar
  28. 28.
    Limas CJ, Olivari M, Goldenberg JF, Levine TB, Bendit DG, Simon A. Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res 1987; 21: 601–605.PubMedCrossRefGoogle Scholar
  29. 29.
    Hasenfuss G, Mulieri LA, Holubarsch C, Pieske B, Just H, Alpert NR. Energetics of calcium in nonfailing and failing human myocardium. Basic Res Cardiol 1992; 87(2): 81–92.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Gerd Hasenfuss
    • 1
  • Burkert Pieske
    • 1
  • Christian Holubarsch
    • 1
  • Norman R. Alpert
    • 2
  • Hanjörg Just
    • 1
  1. 1.Medizinische Klinik III, Universität Freiburg, FRGBurlingtonUSA
  2. 2.Department of Physiology and BiophysicsUniversity of VermontBurlingtonUSA

Personalised recommendations