Skip to main content
SpringerLink
Log in
Book cover

Advances in Myocardiology pp 23–43Cite as

Energy Metabolism of the Heart in Catecholamine-Induced Myocardial Injury

Concentration-Dependent Effects of Epinephrine on Enzyme Release, Mechanical Function, and “Oxygen Wastage”

  • Chapter

Abstract

Epinephrine caused a dose-related release of lactate dehydrogenase (LDH) from the isolated perfused working rat heart. Thus, epinephrine, at 10-8 m, did not increase release of LDH, but at 10-6 m, it gave a peak release of 712 ± 48 mU/g fresh wt. per min (N = 41) 10 min after addition (control: 17 ± 2 mU/g per min, N = 36). The effects of 10-7 m epinephrine (peak release: 159 ± 28 mU/g per min, N = 29) were mimicked by theophylline, 10-3 m. Increased release of LDH was also achieved by dibutyryl cAMP, 5 × 10-4 m (399 ± 67 mU/ g per min, N = 6), but not by cAMP, 5 × 10-4 m. Increased tissue cAMP could be related to the extent of enzyme loss induced by epinephrine or by theophylline. Both tissue cAMP and LDH decreased when propranolol, 10-5 m, was added to epinephrine 10-6 m. Epinephrineinduced enzyme loss was also decreased by halving the perfusate Ca2+ or doubling the perfusate Mg2+ or by verapamil, 2 × 10-7 m, thereby showing a role for Ca2+ entry. However, there was no evidence for excess excitation-coupling with major ATP depletion. Although decreased efficiency of pressure work (“oxygen wastage”) was a graded phenomenon, it was apparent even with epinephrine, 10-8 m. As the epinephrine concentration rose, so did heart rate, coronary flow, oxygen uptake, the degree of “oxygen wastage,” the level of tissue cAMP, and the extent of enzyme release. At 10-7 m epinephrine, the efficiency of pressure work was only 68% of control, but there was no depletion of high-energy phosphate compounds despite marked enzyme loss. Rather, there was a small loss of ATP only at the highest epinephrine concentration (10-6 m) with an increase of phosphocreatine, suggesting that intracellular transfer of energy was impaired. Epinephrine-induced enzyme release and “oxygen wastage” could occur at concentrations below 10-6 m which did not cause detectable depletion of the tissue content of ATP.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bhagat, B., Sullivan, J. M., Fischer, V. W., Nadel, E. M., and Dhalla, N. S. 1978. cAMP activity and isoproterenol-induced myocardial injury in rats. In: T. Kobayashi, Y. Ito, and G. Rona (eds.), Recent Advances in Studies on Cardiac Structure and Metabolism. Vol. 12: Cardiac Adaptation, pp. 465–470. University Park Press, Baltimore.

    Google Scholar 

  2. Bricknell, O. L., and Opie, L. H. 1978. Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion. Circ. Res. 43:102–115.

    Article  PubMed  CAS  Google Scholar 

  3. Ciba-Geigy. 1970. Statistical Methods in Scientific Tables, pp. 172–173. Ciba-Geigy, Basel.

    Google Scholar 

  4. de Leiris, J., and Opie, L. H. 1978. Effect of substrates and of coronary artery ligation on mechanical performance and on release of lactate dehydrogenase and creatine Phosphokinase in isolated working rat hearts. Cardiovasc. Res. 12:585–596.

    Article  PubMed  Google Scholar 

  5. Dhalla, N. S., Yates, J. C., Lee, S. L., and Singh, A. 1978. Functional and subcellular changes in the isolated rat heart perfused with oxidized isoproterenol. J. Mol. Cell Cardiol. 10:31–41.

    Article  PubMed  CAS  Google Scholar 

  6. Fleckenstein, A. 1971. Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In: P. Harris and L. H. Opie (eds.), Calcium and the Heart, pp. 135–188. Academic Press, London, New York.

    Google Scholar 

  7. Fleckenstein, A., Janke, J., Döring, H. J., and Leder, O. 1974. Myocardial fiber necrosis due to intracellular Ca overload—a new principle in cardiac pathophysiology. In: N. S. Dhalla (ed.), Recent Advances in Studies on Cardiac Structure and Metabolism. Vol. 4. Myocardial Biology, pp. 563–580. University Park Press, Baltimore.

    Google Scholar 

  8. Fleckenstein, A., Janke, J., Döring, H. J., and Leder, O. 1975. Key role of Ca in the production of noncoronarogenic myocardial necroses. In: A. Fleckenstein and G. Rona (eds.), Recent Advances in Studies on Cardiac Structure and Metabolism. Vol. 6: Pathophysiology and Morphology of Myocardial Cell Alteration, pp. 21–32. University Park Press, Baltimore.

    Google Scholar 

  9. Gartner, S. L., and Vahouny, G. V. 1972. Effects of epinephrine and cyclic 3′,5′-AMP on perfused rat hearts. Am. J. Physiol. 222:1121–1124.

    PubMed  CAS  Google Scholar 

  10. Gudbjamason, S., Mathes, P., and Ravens, K. G. 1970. Functional compartmentation of ATP and creatine phosphate in heart muscle. J. Mol. Cell Cardiol. 1:325–339.

    Article  Google Scholar 

  11. Higgins, T. J., Allsopp, D., Bailey, P. J. 1980. The effect of extracellular calcium concentrations and Ca-antagonist drugs on enzyme release and lactate production by anoxic heart cell cultures. J. Mol. Cell. Cardiol. 12:909–927.

    Article  PubMed  CAS  Google Scholar 

  12. Horak, A. R., Podzuweit, T., and Opie, L. H. 1980. Cyclic AMP as mediator of catecholamine-induced enzyme release from isolated perfused working rat heart. In: M. Tajuddin, P. K. Das, M. Tarig, and N. S. Dhalla (eds.), Advances in Myocardiology, Vol. 1, pp. 367–373. University Park Press, Baltimore.

    Google Scholar 

  13. Kannengiesser, G. J., Opie, L. H., and van der Werff, T. J. 1979. Impaired cardiac work and oxygen uptake after reperfusion of regional ischaemic myocardium. J. Mol. Cell. Cardiol. 11:197–207.

    Article  PubMed  CAS  Google Scholar 

  14. Krebs, H. A., and Henseleit, K. 1932. Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe Seylers Z. Physiol. Chem. 210:33–66.

    Article  CAS  Google Scholar 

  15. Langendorff, O. 1895. Untersuchungen am überlebenden Saügertierherzen. Pfluegers Arch. 61:291–332.

    Article  Google Scholar 

  16. Miller, J. P., Boswell, K. H., Meyer, R. B., Christensen, L. F., and Robins, R. K. 1980. Synthesis and enzymatic and inotropic activity of some new 8-substituted and 6,8-disub-stituted derivatives of adenosine cyclic 3′,5′-monophosphate. J. Med. Chem. 23:242–251.

    Article  PubMed  CAS  Google Scholar 

  17. Moravec, J., Corsin, A., Owen, P., and Opie, L. H. 1974. Effect of increased aortic perfusion pressure on autofluorescent emission of the isolated rat heart. J. Mol. Cell. Cardiol. 6:187–200.

    Article  PubMed  CAS  Google Scholar 

  18. Neely, J. R., Liebermeister, H., and Morgan, H. E. 1967. Effect of pressure development on membrane transport of glucose in isolated rat heart. Am. J. Physiol. 212:815–822.

    PubMed  CAS  Google Scholar 

  19. Opie, L. H. 1965. Coronary flow rate and perfusion pressure as determinants of mechanical function and oxidative metabolism of isolated perfused rat heart. J. Physiol. (Lond.) 180:529–541.

    CAS  Google Scholar 

  20. Opie, L. H., and Bricknell, O. L. 1979. Role of glycolytic flux in effect of glucose idecreasing fatty-acid-induced release of lactate dehydrogenase from isolated coronary-li-gated rat heart. Cardiovasc. Res. 13:693–702.

    Article  PubMed  CAS  Google Scholar 

  21. Opie, L. H., Mansford, K. R. L., and Owen, P. 1971. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats. Biochem. J. 124:475–490.

    PubMed  CAS  Google Scholar 

  22. Opie, L. H., and Owen, P. 1975. Assessment of mitochondrial free NAD/NADH ratios and oxaloacetate concentrations during increased mechanical work in isolated perfused rat heart during production or uptake of ketone bodies. Biochem. J. 148:403–415.

    PubMed  CAS  Google Scholar 

  23. Opie, L. H., Thandroyen, F. T., Muller, C., and Bricknell, O. L. 1979. Adrenaline-induced “oxygen-wastage” and enzyme release from working rat heart. Effects of calcium antagonism, β-blockade, nicotinic acid, and coronary artery ligation. J. Mol. Cell. Cardiol. 11:1073–1094.

    Article  PubMed  CAS  Google Scholar 

  24. Reuter, H. 1974. Localization of β-adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J. Physiol. (Lond.) 242:429–451.

    CAS  Google Scholar 

  25. Rona, G., Chappel, C. L, Balazs, T., and Gaundry, R. 1959. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Arch. Pathol. (Chicago) 67:443–445.

    CAS  Google Scholar 

  26. Sutherland, E. W., Robison, G. A., and Butcher, R. W. 1968. Some aspects of the biological role of adenosine-3′,5′-monophosphate. Circulation 37:279–306.

    Article  CAS  Google Scholar 

  27. Urthaler, F., and James, T. N. 1976. Both direct and neurally mediated components of the chronotropic actions of aminophylline. Chest 70:24–32.

    Article  PubMed  CAS  Google Scholar 

  28. Vetter, N. J., Strange, R. C., Adams, W., and Oliver, M. F. 1974. Initial metabolic and hormonal response to acute myocardial infarction. Lancet 1:284–288.

    Article  PubMed  CAS  Google Scholar 

  29. Waldenström, A. P., Hjalmarson, A. C., and Thornell, L. T. 1978. A possible role of noradrenaline in the development of myocardial infarction. An experimental study in the isolated rat heart. Am. Heart J. 95:43–51.

    Article  PubMed  Google Scholar 

  30. Williamson, J. R., Ford, C., Illingworth, J., and Safer, B. 1976. Coordination of citric acid cycle activity with electron transport flux. Circ. Res. 38(Suppl. 1):39–48.

    Google Scholar 

  31. WoUenberger, A., Ristau, O., and Schoffa, G. 1960. Eine einfache Technik der extrem schnellen abkühling grösserer Gewebestücke. Pfluegers Arch. 270:399–412.

    Article  Google Scholar 

  32. Wroblewski, F., and La Due, J. S. 1955. Lactic dehydrogenase activity in blood. Proc. Soc. Exp. Biol. Med. 90:210–213.

    PubMed  CAS  Google Scholar 

  33. Young, R. C., Thomas, M., Evans, M. E., and Opie, L. H. 1972. Catecholamines and myocardial infarction. In: E. Bajusz and G. Rona (eds.), Recent Advances in Studies on Cardiac Structure and Metabolism. Vol. 1: Myocardiology, pp. 163–168. University Park Press, Baltimore.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Ischaemic Heart Disease Research Unit, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    A. R. Horak & L. H. Opie

Authors
  1. A. R. Horak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. H. Opie
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cardiology Research Center, Academy of Medical Sciences, Moscow, USSR

    E. Chazov M.D.

  2. Institute of Pathology, McGill University, Montreal, Quebec, Canada

    G. Rona M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer Science+Business Media New York

About this chapter

Cite this chapter

Horak, A.R., Opie, L.H. (1983). Energy Metabolism of the Heart in Catecholamine-Induced Myocardial Injury. In: Chazov, E., Saks, V., Rona, G. (eds) Advances in Myocardiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4441-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-4441-5_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-4443-9

  • Online ISBN: 978-1-4757-4441-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation