Bulletin of Experimental Biology and Medicine

, Volume 166, Issue 5, pp 689–694 | Cite as

Structural Analysis of the Myocardium in Experimental Anthracycline-Induced Cardiomyopathy Combined with Adrenergic Stimulation

  • E. L. LushnikovaEmail author
  • O. P. Molodykh
  • D. B. Nikityuk
  • D. E. Semenov
  • M. G. Klinnikova

We studied dynamic changes in the total number of cardiomyocytes and the character of structural lesions in the myocardium in rats with modeled anthracycline-induced cardiomyopathy provoked by a single injection of doxorubicin in a dose of 10 mg/kg alone or in combination with subsequent adrenergic stimulation. The injections of epinephrine during the development of anthracycline-induced cardiomyopathy resulted in more pronounced loss of body weight, stronger decrement of the heart weight, and more severe decrease of the cardiomyocyte count in comparison with the corresponding changes induced by doxorubicin alone. The basic lesions of cardiomyocytes in anthracycline-induced cardiomyopathy are the lytic alterations and subsegmental contractures; in contrast, combined use of doxorubicin and epinephrine provoked degree II and III contractures. The revealed necrobiotic changes of cardiomyocytes resulted in their death and pronounced decrease of their number at the initial terms of the study. Hypertrophy observed at later terms of the experiments in parallel with partial recovery of cardiomyocyte number reflected the development of regenerative and adaptivecompensatory processes induced by massive death and elimination of the parenchymatous cells (up to 36-37% of population).

Key Words

anthracycline-induced cardiomyopathy adrenergic lesions cardiac remodeling number of cardiomyocytes in the heart 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Klinnikova MG, Lushnikova EL, Koldysheva EV, Tolstikova TG, Sorokina IV, Yuzhik EI, Mzhelskaya MM. Cardiotoxic and Dyslipidemic Effects of Doxorubicin and Betulinic Acid Amide. Bull. Exp. Biol. Med. 2016;162(2):277-282.CrossRefGoogle Scholar
  2. 2.
    Lushnikova EL, Klinnikova MG, Molodykh OP, Nepomnyashchikh LM. Ultrastructural criteria of cardiomyocyte regeneratory and plastic insufficiency in anthracycline cardiomyopathy. Bull. Exp. Biol. Med. 2005;139(4):472-476.CrossRefGoogle Scholar
  3. 3.
    Lushnikova EL, Tolstikova TG, Nepomnyashchikh LM, Klinnikova MG, Molodykh OP, Sviridov EA, Sorokina IV, Zhukova NA. Cardiomyocyte count in rat myocardium under the effect of antitumor agents cyclophosphamide and triterpenoids. Bull. Exp. Biol. Med. 2007;144(3):355-361.CrossRefGoogle Scholar
  4. 4.
    Nepomnyashchikh LM, Lushnikova EL, Semenov DE. Regeneratory and Plastic Insufficiency of the Heart. Morphological Bases and Molecular Mechanisms. Moscow, 2003. Russian.Google Scholar
  5. 5.
    Semenova LA, Nepomnyashchikh LM, Semenov DE. Morphology of Plastic Insufficiency of Cardiomyocytes. Novosibirsk, 1985. Russian.Google Scholar
  6. 6.
    Bajaj G, Sharma RK. TNF-alpha-mediated cardiomyocyte apoptosis involves caspase-12 and calpain. Biochem. Biophys. Res. Commun. 2006;345(4):1558-1564.CrossRefGoogle Scholar
  7. 7.
    Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A. Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review. Health Technol. Assess. 2007;11(27):1-84.CrossRefGoogle Scholar
  8. 8.
    Campos EC, O’Connell JL, Malvestio LM, Romano MM, Ramos SG, Celes MR, Prado CM, Simões MV, Rossi MA. Calpain-mediated dystrophin disruption may be a potential structural culprit behind chronic doxorubicin-induced cardiomyopathy. Eur. J. Pharmacol. 2011;670(2-3):541-553.CrossRefGoogle Scholar
  9. 9.
    Chang YT, Huang WC, Cheng CC, Ke MW, Tsai JS, Hung YM, Huang YM, Huang MS, Wann SR. Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model. Bosn. J. Basic Med. Sci. 2018. doi:
  10. 10.
    Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155-162.CrossRefGoogle Scholar
  11. 11.
    Hakamata N, Hamada H, Ohsuzu F, Nakamura H. Cardiac beta-adrenergic signaling pathway alteration in isoproterenolinduced cardiac hypertrophy in male Sprague-Dawley rats. Jpn. Heart J. 1997;38(6):849-857.CrossRefGoogle Scholar
  12. 12.
    Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, Inanc T, Oguzhan A, Eryol NK, Topsakal R, Ergin A. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J. Am. Coll. Cardiol. 2006;48(11):2258-2262.CrossRefGoogle Scholar
  13. 13.
    Sun A, Cheng Y, Zhang Y, Zhang Q, Wang S, Tian S, Zou Y, Hu K, Ren J, Ge J. Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction through detoxification of 4-HNE and suppression of autophagy. J. Mol. Cell. Cardiol. 2014;71:92-104.CrossRefGoogle Scholar
  14. 14.
    Takemura G, Fujiwara H. Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog. Cardiovasc. Dis. 2007;49(5):330-352.CrossRefGoogle Scholar
  15. 15.
    Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann. Intern. Med. 1979;91(5):710-717.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. L. Lushnikova
    • 1
    Email author
  • O. P. Molodykh
    • 1
  • D. B. Nikityuk
    • 1
  • D. E. Semenov
    • 1
  • M. G. Klinnikova
    • 1
  1. 1.Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational MedicineNovosibirskRussia

Personalised recommendations