Morphologic Assessment of Cardiac Lesions Caused by Anthracyclines

  • V. J. Ferrans
Part of the Developments in Oncology book series (DION, volume 10)

Abstract

The clinical use of daunorubicin and doxorubicin, two anti-neoplastic drugs of the anthracycline family, has been limited by the development of cardiotoxic effects. These can be subdivided into acute, subacute and chronic depending upon their temporal relationship to the administration of the drugs. The acute effects consist of hypotension, tachycardia and various arrhythmias, which develop within minutes after intravenous administration. The subacute effects are characterized by fibrinous pericarditis or myocardial dysfunction, which occur within four weeks of the first or second dose of the drug. The chronic effects develop only after several weeks or months of treatment, sometimes after the course of therapy has been completed, and are manifested by the insidious onset of severe, often fatal congestive heart failure.

Keywords

Toxicity Glutathione Superoxide Histamine NADPH 

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References

  1. 1.
    Young RC, Ozols RF, Myers CE. The anthracycline antineoplastic drugs. N Engl J Med 305:139, 1981.PubMedCrossRefGoogle Scholar
  2. 2.
    Herman E, Young R, Krop S. Doxorubicin-induced hypotension in the Beagle dog. Agents Actions 8:551, 1978.PubMedCrossRefGoogle Scholar
  3. 3.
    Bristow MR, Minobe WA, Billingham ME, Marmor JB, Johnson GA, Ishimoto BM, Sageman WS, Daniels JR. Anthracycline-associated cardiac and renal damage in rabbits: evidence for mediation by vasoactive substances. Lab Invest 45:157, 1981.PubMedGoogle Scholar
  4. 4.
    Regal E, Kaliner M, El-Hage A, Ferrans VJ, Kawanami O, Herman EH. Anthracycline-induced histamine release from rat mast cells. Agents Actions (in press).Google Scholar
  5. 5.
    Gandolfi A. Cardiotossicitd cronica da adriamicina: studio morfologico ultrastrutturale sul miocardio ventricolare e sul sistema di conduzione del cuore di coniglio. Ateneo Parmense [Acta Biomed] 47:69, 1976.Google Scholar
  6. 6.
    Herman EH, Ferrans VJ. Unpublished observations.Google Scholar
  7. 7.
    Lambertenghi-Deliliers G, Zanon PL, Pozzoli EF, Bellini O. Myocardial injury induced by a single dose of adriamycin: an electron microscopic study. Tumori 62:517, 1976.PubMedGoogle Scholar
  8. 8.
    Merski A, Daskal I, Busch H. Effects of adriamycin on ultrastructure of nucleoli in the heart and liver cells of the rat. Cancer Res 36:1580, 1976.PubMedGoogle Scholar
  9. 9.
    Daskal Y, Woodard C, Crooke ST, Busch H. Comparative ultrastructural studies of nucleoli of tumor cells treated with Adriamycin and the newer anthracyclines, Carminomycin and Marcellomycin. Cancer Res 38:467, 1978.PubMedGoogle Scholar
  10. 10.
    Unuma T, Senda R, Muramatsu M. Mechanism of nucleolar segregationdifferences in effects of actinomycin D and cycloheximide on nucleoli of rat liver cells. J Electron Microsc (Tokyo) 22:205, 1973.Google Scholar
  11. 11.
    Buja LM, Ferrans VJ, Mayer RJ, Roberts WC, Henderson ES. Cardiac ultrastructural changes induced by daunorubicin therapy. Cancer 32:771, 1973.PubMedCrossRefGoogle Scholar
  12. 12.
    Egorin MJ, Hildebrand RC, Cimino EF, Bachur NR. Cytofluorescence localization of adriamycin and daunorubicin. Cancer Res 34:2243, 1974.PubMedGoogle Scholar
  13. 13.
    Buja LM, Ferrans VJ, Rabson AS. Letter: Unusual nuclear alterations. Lancet 1:402, 1974.PubMedCrossRefGoogle Scholar
  14. 14.
    Bristow MR, Thompson PO, Martin RP, Mason JW, Billingham ME, Harrison DC. Early anthracycline cardiotoxicity. Am J Med 65:823, 1978.PubMedCrossRefGoogle Scholar
  15. 15.
    Lefrak EA, Pitha J, Rosenheim S, Gottlieb J. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32:302, 1973.PubMedCrossRefGoogle Scholar
  16. 16.
    Cortes EP, Lutman G, Wanka J, Wang JJ, Pickren J, Wallace J, Holland JF. Adriamycin (NSC-123127) cardiotoxicity. A clinicopathologic correlation. Cancer Treat Rep 6:215, 1975.Google Scholar
  17. 17.
    Gilladoga AC, Manuel C, Tan CC, Wollner N, Murphy ML. Cardiotoxicity of adriamycin (NSC-123127) in children. Cancer Treat Rep 6:209, 1975.Google Scholar
  18. 18.
    Minow RA, Benjamin RS, Lee ET, Gottlieb JA. Adriamycin cardiomyopathy-risk factors. Cancer 39:1397, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    Halazun JF, Wagner HR, Gaeta JF, Sinks LF. Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia. Cancer 33: 545, 1974.PubMedCrossRefGoogle Scholar
  20. 20.
    Gilladoga AC, Manuel C, Tan C, Wollner N, Sternberg SS, Murphy ML. The cardiotoxicity of adriamycin and daunomycin in children. Cancer 37:1070, 1976.PubMedCrossRefGoogle Scholar
  21. 21.
    Von Hoff DO, Rozencweig M, Layard M, Slavik M, Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med 62:200, 1977.CrossRefGoogle Scholar
  22. 22.
    Billingham ME, Mason JW, Bristow MR, Daniels JR. Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 62:865, 1978.PubMedGoogle Scholar
  23. 23.
    Ferrans VJ. Overview of cardiac pathology in relation to anthracycline cardiotoxicity. Cancer Treat Rep 62:955, 1978.PubMedGoogle Scholar
  24. 24.
    Chalcroft SCW, Gavin JB, Herdson PB. Fine structural changes in rat myocardium induced by daunorubicin. Pathology 5:99, 1973.PubMedCrossRefGoogle Scholar
  25. 25.
    Rosenoff SH, Olson HM, Young OM, Bostick F, Young RC. Adriamycininduced cardiac damage in the mouse. A small animal model of cardiotoxicity. JNCI 55:191, 1975.PubMedGoogle Scholar
  26. 26.
    Jaenke RS. An anthracycline antibiotic-induced cardiomyopathy in rabbits. Lab Invest 30:292, 1974.PubMedGoogle Scholar
  27. 27.
    Olson HM, Young OM, Prieur OJ, Le Roy AF, Reagan RL. Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. Am J Pathol 77:439, 1974.PubMedGoogle Scholar
  28. 28.
    Ferrans VJ, Buja LM, Levitsky S, Williams WH, McIntosh CL, Roberts WC. Cardiac preservation: a morphologic study. Recent Adv Stud Cardiac Struct Metab 1:351, 1972.PubMedGoogle Scholar
  29. 29.
    Buja LM, Ferrans VJ, Maron BJ. Intracytoplasmic junctions in cardiac muscle cells. Am J Pathol 74:613, 1974.PubMedGoogle Scholar
  30. 30.
    Ferrans VJ, Thiedemann K-U, Maron BJ, Roberts WC. Spherical microparticles in human myocardium. An ultrastructural study. Lab Invest 35:349, 1976.PubMedGoogle Scholar
  31. 31.
    Gosalvez M, van Rossum GOV, Blanco MF. Inhibition of sodiumpotassium-activated adenosine 5’-triphosphatase and ion transport by Adriamycin. Cancer Res 39:257, 1979.PubMedGoogle Scholar
  32. 32.
    Van Vleet JF, Ferrans VJ, Weirich WE. Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants. Am J Pathol 99:13, 1980.PubMedGoogle Scholar
  33. 33.
    Van Vleet JF, Greenwood LA, Ferrans VJ. Pathologic features of adriamycin toxicosis in young pigs: nonskeletal lesions. Am J Vet Res 40:1537, 1979.PubMedGoogle Scholar
  34. 34.
    Bristow MR, Mason JW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy. Evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med 88:168, 1978.PubMedGoogle Scholar
  35. 35.
    Isner JM, Ferrans VJ, Cohen SR, Witkind BG, Virmani R, Gottdiener JS, Roberts WC. Variability of cardiac histologic toxicity in patients treated with anthracycline chemotherapy. Am J Cardiol 45: 396, 1980.CrossRefGoogle Scholar
  36. 36.
    Ferrans VJ, Hibbs RG, Weily HS, Weilbaecher DG, Walsh JJ, Burch GE. A histochemical and electron microscopic study of epinephrineinduced myocardial necrosis. J Mol Cell Cardiol 1:11, 1970.PubMedCrossRefGoogle Scholar
  37. 37.
    Ferrans VJ, Hibbs RG, Walsh JJ, Burch GE. Histochemical and electron microscopical studies on the cardiac necroses produced by sympathomimetic agents. Ann NY Acad Sci 156:309, 1969.PubMedCrossRefGoogle Scholar
  38. 38.
    Franco-Browder S, Guerrero M, Gorodezky M, Bravo LM, Aceves S. Lesiones miocardicas producidas por liberadores de histamina en ratas. Arch Inst Cardiol Mex 30:720, 1960.PubMedGoogle Scholar
  39. 39.
    Myers CE, McGuire WP, Liss RH, Ifrim I, Grotzinger K, Young RC. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science 197:165, 1977.PubMedCrossRefGoogle Scholar
  40. 40.
    Myers CE, McGuire WP, Young RC. Adriamycin: amelioration of toxicity by a-tocopherol. Cancer Treat Rep 60:961, 1976.PubMedGoogle Scholar
  41. 41.
    Wang Y, Madanat FF, Kimball JC, Gleiser CA, Ali MK, Kaufman MW, Van Eys J. Effect of vitamin E against adriamycin-induced toxicity in rabbits. Cancer Res 40:1022, 1980.PubMedGoogle Scholar
  42. 42.
    Breed JGS, Zimmerman ANE, Dormans JAM, Pinedo HM. Failure of the antioxidant vitamin E to protect against adriamycin-induced cardiotoxicity in the rabbit. Cancer Res 40:2033, 1980.PubMedGoogle Scholar
  43. 43.
    Van Vleet JF, Greenwood L, Ferrans VJ, Rebar AH. Effect of seleniumvitamin E on adriamycin-induced cardiomyopathy in rabbits. Am J Vet Res 39:997, 1978.PubMedGoogle Scholar
  44. 44.
    Van Vleet JF, Ferrans VJ. Cutaneous lesions and hematologic alterations in chronic adriamycin intoxication in dogs with and without vitamin E and selenium supplementation. Am J Vet Res 41: 691, 1980.PubMedGoogle Scholar
  45. 45.
    Van Vleet JF, Ferrans VJ. Evaluation of vitamin E and selenium protection against chronic adriamycin toxicity in rabbits. Cancer Treat Rep 64:315, 1980.PubMedGoogle Scholar
  46. 46.
    Bertazzoli C, Sala L, Solcia E, Ghione M. Experimental adriamycin cardiotoxicity prevented by ubiquinone in vivo in rabbits. Int Res Commun Sys Med Sci 3:468, 1975.Google Scholar
  47. 47.
    Caulfield JB, Shelton RW, Burke JF. Cytotoxic effects of oxygen on striated muscle. Arch Pathol 94:127, 1972.PubMedGoogle Scholar
  48. 48.
    Fajardo LF, Stewart JR. Pathogenesis of radiation-induced myocardial fibrosis. Lab Invest 29:244, 1973.PubMedGoogle Scholar
  49. 49.
    FajardO LF, Eltringham JR, Stewart JR. Combined cardiotoxicity of Adriamycin and X-radiation. Lab Invest 34:86, 1976.PubMedGoogle Scholar
  50. 50.
    Eltringham JR, Fajardo LF, Stewart R. Adriamycin cardiomyopathy: enhanced cardiac damage in rabbits with combined drug and cardiac irradiation. Radiology 115:471, 1975.PubMedGoogle Scholar
  51. 51.
    Billingham ME, Bristow MR, Glatstein E, Mason JW, Masek MA, Daniels JR. Adriamycin cardiotoxicity: endomyocardial biopsy evidence of enhancement by irradiation. Am J Surg Pathol 1:17, 1977.PubMedCrossRefGoogle Scholar
  52. 52.
    Van Vleet JF, Ferrans VJ, Ruth GR. Ultrastructural alterations in nutritional cardiomyopathy of selenium-vitamin E deficient swine. I. Fiber lesions. Lab Invest 37:188, 1977.PubMedGoogle Scholar
  53. 53.
    Van Vleet JF, Ferrans VJ, Ruth GR. Ultrastructural alterations in nutritional cardiomyopathy of selenium-vitamin E deficient swine. II. Vascular lesions. Lab Invest 37:201, 1977.PubMedCrossRefGoogle Scholar
  54. 54.
    Myers CE, Gianni L, Simone CB, Hendrickson M, Klecker R, Greene R. Oxidative destruction of erythrocyte ghost membranes catalyzed by the doxorubicin-iron complex. Biochemistry (submitted).Google Scholar
  55. 55.
    Herman EH, Ferrans VJ. Reduction of chronic doxorubicin cardiotoxicity in dogs by pretreatment with (±)-1,2-bis(3,5-dioxopiperazinyl-l-yl)propane (ICRF-187). Cancer Res 41: 3436, 1981.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, The Hague 1982

Authors and Affiliations

  • V. J. Ferrans

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