Skip to main content
SpringerLink
Log in
Book cover

Myocardial Injury pp 509–518Cite as

A Molecular Biologic Approach to Cardiac Toxicology

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 161))

Abstract

Molecular biology seeks to depict biological function in terms of discrete events, individually accessible to biochemical study. With the myocardial cell this approach has had some success. The affinity of receptors for a variety of drugs, the ionic basis for signal transmission across the sarcolemmal membrane, and the enzymatic components of the various membranes that control internal calcium, have been studied and provide a rationale for at least some of the reversible, pharmacologically induced dysfunctions that represent the side effects of conventional drugs on this cell. This symposium, however, deals largely with chemical agents which initiate sequences of incompletely understood events that lead ultimately to irreversible tissue damage and cell death. Among these effects, the myocardial necrosis produced by suprapharmacological concentrations of isoproterenol has been of special interest because its production may have some elements in common with infarction or ischemic damage and because it induces resistance to further chemical damage.

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   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
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. BALAZS, T., OHTAKE, S. & NOBLE, J.F. The development of resistance to the ischemic cardiopathic effect of isoproterenol. Toxicology and Applied Pharmacology21, 200–213 (1972).

    Article  PubMed  CAS  Google Scholar 

  2. BLOOM, S. Reversible and irreversible injury; Calcium as a major determinant. In Cardiac Toxicology, Vol. 1, T. Balazs, Ed., pp. 179–201. Boca Raton: CRC Press (1981).

    Google Scholar 

  3. BLOOM, S. & CANCILLA, P. Myocytolysis and mitochondrial calcification in rat myocardium after low doses of isoproterenol. American Journal of Pathology54, 373–391 (1969).

    PubMed  CAS  Google Scholar 

  4. BLOOM, S. & DAVIS, D. Calcium as mediator of isoproterenol-induced myocardial necrosis. American Journal of Pathology69, 459–470 (1972).

    PubMed  CAS  Google Scholar 

  5. BRISTOW, M.R., MASON, J.W., BILLINGHAM, M.E. & DANIELS, J.R. Doxorubicin cardiomyopathy; Evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Annals of Internal Medicine88, 168–175 (1978).

    PubMed  CAS  Google Scholar 

  6. BUETTNER, G.R. & OBERLEY, L.W. Considerations in the spin trapping of superoxide and hydroxyl radical in aqueous systems using 5,5-dimethyl-l-pyrroline-1-oxide. Biochemical and Biophysical Research Communications83, 69–74 (1978).

    Article  PubMed  CAS  Google Scholar 

  7. DEMOPOULOS, H.B., FLAMM, E.S., PIETRONIGRO, D.D. & SELIGMAN, M.L. The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiologica Scandinavica Supplementum492, 91–119 (1980).

    PubMed  CAS  Google Scholar 

  8. DOROSHOW, J.H., LOCKER, G.Y. & MYERS, G.E. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: Alterations produced by doxorubicin. Journal of Clinical Investigation65, 128–135 (1980).

    Article  PubMed  CAS  Google Scholar 

  9. EVANS, C.A. Spin trapping. Aldrichimica Acta12, 23–29 (1979).

    CAS  Google Scholar 

  10. FLECKENSTEIN, A., JANKE, J., DORING, H. & LEDER, O. Myocardial fiber necrosis due to intracellular calcium overload — a new principle in cardiac pathophysiology. Recent Advances in Studies on Cardiac Structure and Metabolism4, 563–580 (1974).

    PubMed  CAS  Google Scholar 

  11. GOODMAN, J. & HOCHSTEIN, P. Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochemical and Biophysical Research Communications77, 797–803 (1977).

    Article  PubMed  CAS  Google Scholar 

  12. HERMAN, E. Cardiotoxicity of anti-neoplastic drugs. In Cardiac Toxicology, Vol. 2, T. Balazs, Ed., pp. 165–189. Boca Raton: CRC Press (1981).

    Google Scholar 

  13. ITO, K., KARAKI, H. & URAKAWA, N.. Effects of palytoxin on mechanical and electrical activities of guinea pig papillary muscle. Japanese Journal of Pharmacology29, 467–476 (1979).

    Article  PubMed  CAS  Google Scholar 

  14. JANZEN, E.G. A critical review of spin trapping in biological systems. In Free Radicals in Biology, Vol. 4, W.A. Pryor, Ed., pp. 115–154. New York: Academic Press (1980).

    Google Scholar 

  15. JANZEN, E.G., WANG, Y.Y. & SHETTY, R.V. Spin trapping with a-pyridyl-1-oxide N-tert-butyl nitrones in aqueous solution. A unique electron spin resonance spectrum for the hydroxyl radical adduct. Journal of the American Chemical Society100, 2923–2925 (1978).

    Article  CAS  Google Scholar 

  16. KAPPUS, H. & SIES, H. Toxic drug effects associated with oxygen metabolism: Redox cycling and lipid peroxidation. Experientia37, 1233–1241 (1981).

    Article  PubMed  CAS  Google Scholar 

  17. KLUGMANN, S., BARTOLI KLÜGMANN, F., DECORTI, G., GORI, D., SYLVESTRI, F. & CAMERINI, F. Adriamycin experimental cardiomyopathy in Swiss mice. Different effects of two calcium antagonistic drugs on ADM-induced cardiomyopathy. Pharmacological Research Communications13, 769–776 (1981).

    Article  PubMed  CAS  Google Scholar 

  18. LAI, E.K., McKAY. P.B., NOGUCHI, T. & FONG, K. In vivo spin trapping of trichloromethyl radicals formed from CCl4. Biochemical Pharmacology28, 2231–2235 (1979).

    Article  PubMed  CAS  Google Scholar 

  19. LEHR, D. Studies on the cardiotoxicity of alpha and beta adrenergic amines. In Cardiac Toxicology, Vol. 2, T. Balazs, Ed., pp. 75–113. Boca Raton: CRC Press (1981).

    Google Scholar 

  20. LEHR, D., CHAU, R. & IRENE, S. Possible role of magnesium loss in the pathogenesis of myocardial fiber necrosis. Recent Advances in Studies on Cardiac Structure and Metabolism 6, 95–109 (1975).

    PubMed  CAS  Google Scholar 

  21. LUCCHESI, B., BURNREISTER, W., LOMAS, T. & ABRAMS, G. Ischemic changes in the canine heart as affected by the dimethyl quaternary analog of propranolol, UM 272. Journal of Pharmacology and Experimental Therapeutics199, 310–328 (1976).

    PubMed  CAS  Google Scholar 

  22. McCORD, J.M. Superoxide, superoxide dismutase and oxygen toxicity. In Reviews in Biochemical Toxicology, Vol. 1., E. Hodgson, J.R. Bend & R.M. Philpot, Eds., pp. 109–124. New York: Elsevier/North Holland (1979).

    Google Scholar 

  23. MOORE, R.E. & BARTOLINI, G. Structure of palytoxin. Journal of the American Chemical Society103, 2491–2494 (1981).

    Article  CAS  Google Scholar 

  24. OLSON, H.M., YOUNG, D.M., PRIEUR, D.J., LeROY, A.F. & REAGAN, R.L. Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. American Journal of Pathology 77, 439–454 (1974).

    PubMed  CAS  Google Scholar 

  25. OLSON, R.D., BOERTH, R.C., GERBER, J.G. & NILES, A.S. Mechanism of adriamycin eardiotoxicity: Evidence for oxidative stress. Life Sciences29, 1393–1401 (1981).

    Article  PubMed  CAS  Google Scholar 

  26. PARKS, D.A., BÜLKLEY, G.B., GRANGER, D.N., HAMILTON, S.R. & McCORD, J.M. Ischemic injury in the cat small intestine: Role of superoxide radicals. Gastroenterology 82, 9–15 (1982).

    PubMed  CAS  Google Scholar 

  27. REIMER, K.A., RASMUSSEN, M.M. & JENNINGS, R.B. On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs. American Journal of Cardiology37, 520–527 (1976).

    Article  PubMed  CAS  Google Scholar 

  28. ROSEN, G.M. & RAUCKMAN, E.J. Spin trapping of free radicals during hepatic microsomal lipid peroxidation. Proceedings of the National Academy of Sciences, USA78, 7346–7349 (1981).

    Article  CAS  Google Scholar 

  29. ROSSI, C.S. & LEHNINGER, A.L. Stoichiometric relationships between accumulation of ions by mitochondria and the energy-coupling sites in the respiratory chain. Biochemische Zeitschrift338, 698–713 (1963).

    PubMed  CAS  Google Scholar 

  30. ROY, R.S. & McCORD, J.M. Ischemic-induced conversion of xanthine dehydrogenase to xanthine oxidase. Federation Proceedings 41, 767 (1982).

    Google Scholar 

  31. SELYE, H. The Chemical Prevention of Necrosis. New York: Ronald Press (1958).

    Google Scholar 

  32. TSIEN, R.Y. New calcium indicators and buffers with high selectivity against magnesium and protons. Design, synthesis, and properties of prototype structures. Biochemistry 19, 2396–2404 (1980).

    Article  PubMed  CAS  Google Scholar 

  33. TSIEN, R.Y. A non-disruptive technique for loading calcium buffers and indicators into cells. Nature290, 527 (1981).

    Article  PubMed  CAS  Google Scholar 

  34. VAN VLEET, J.F., GREENWOOD, L., FERRANS, V.J. & REBAR, A.H. Effect of selenium-vitamin E on adriamycin-induced cardiomyopathy in rabbits. American Journal of Veterinary Research 39, 997–1010 (1978).

    PubMed  Google Scholar 

  35. VICK, J.A. & WILES, J.S. The mechanism of action and treatment of palytoxin poisoning. Toxicology and Applied Pharmacology 34, 214–223 (1975).

    Article  PubMed  CAS  Google Scholar 

  36. WAUD, W.R. & RAJAGOPALAN, K.V. The mechanism of conversion of rat liver xanthine dehydrogenase from an NAD+-dependent form (type D) to an 02-dependent form (type 0). Archives of Biochemistry and Biophysics172, 365–379 (1976).

    Article  PubMed  CAS  Google Scholar 

  37. WEXLER, B.C. & McMURTRY, J.P. Allopurinol amelioration of the pathophysiology of acute myocardial infarction in rats. Atherosclerosis39, 71–87 (1981).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Drug Biology, Bureau of Drugs, Food and Drug Administration, Washington, D.C., 20204, USA

    Elwood O. Titus

Authors
  1. Elwood O. Titus
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Louisiana State University Medical Center, New Orleans, Louisiana, USA

    John J. Spitzer

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Plenum Press, New York

About this chapter

Cite this chapter

Titus, E.O. (1983). A Molecular Biologic Approach to Cardiac Toxicology. In: Spitzer, J.J. (eds) Myocardial Injury. Advances in Experimental Medicine and Biology, vol 161. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4472-8_30

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-4472-8_30

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-4474-2

  • Online ISBN: 978-1-4684-4472-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation