Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin

Eugene H. Herman, Jun Zhang, Steven E. Lipshultz, Nader Rifai, Douglas Chadwick, Kazuyo Takeda, Zu Xi Yu, Victor J. Ferrans

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Abstract

Purpose: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. Materials and Methods: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. Results: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. Conclusion: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.

Original languageEnglish (US)
Pages (from-to)2237-2243
Number of pages7
JournalJournal of Clinical Oncology
Volume17
Issue number7
DOIs
StatePublished - Jul 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Herman, E. H., Zhang, J., Lipshultz, S. E., Rifai, N., Chadwick, D., Takeda, K., Yu, Z. X., & Ferrans, V. J. (1999). Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin. Journal of Clinical Oncology, 17(7), 2237-2243. https://doi.org/10.1200/jco.1999.17.7.2237