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

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 cTn T 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 myocard ial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of fi ve and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. A ll animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy sco res correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cT nT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respect ively). 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 incr eases in the severity of the cardiomyopathy scores. Conclusion: cTnT is released from doxorubicin-damaged myocytes. Measurement s of serum levels of this protein seem to provide a sensitive means for ass essing the early cardiotoxicity of doxorubicin. (C) 1999 by American Societ y of Clinical Oncology.