Additional studies were made of the relationship between changes in serum levels of troponin-T and the development of doxorubicin-induced cardiac lesions in spontaneously hypertensive rats (SHR) given cumulative doses of 2 to 12 mg/kg of the drug. Administration of 2 and 4 mg/kg of doxorubicin resulted in doubling of the normal level of troponin-T, but not in the development of consistent histologic changes. Administration of 6 mg/kg of doxorubicin led to highly significant elevations in troponin-T levels in serum, but caused only minimal histologic changes. Much greater elevations in troponin-T levels and more severe tissue alterations were produced by 8 to 12 mg/kg of doxorubicin. All of these changes were associated with dose-dependent decreases in the intensity of staining for troponin-T in cardiac myocytes, as determined by confocal microscopy. Thus, the study showed that serum troponin-T levels are sensitive markers for doxorubicin-induced cardiac damage in SHR.
