Studies were made to compare the immunohistochemical changes related to the losses of cardiac troponin-T (cTnT) and cardiac troponin-I (cTnI)from the cardiac myocytes of spontaneously hypertensive rats (SHR) treated with cumulative doses of doxorubicin ranging from 2 to 12 mg/kg of doxorubicin (DXR). Serum levels of both cTnT and cTnI are elevated in patients treated with DXR. However, immunofluorescent labeling of myocytes to detect troponin release has been studied only with respect to cTnT. This study was undertaken to compare labeling for cTnI and cTnT in DXR cardiomyopathy. SHR received 1 mg/kg DXR or saline for 2, 4, 6, 8, 10, or 12 weeks. Fluorescent labeling for cTnT and cTnI was performed, using mouse monoclonal antibodies and an FITC-conjugated secondary antibody, on paraffin sections of formalin-fixed tissue. Both antibodies labeled the I bands of myocytes (more clearly with cTnI than with cTnT); intercalated disks showed labeling only for cTnI. Labeling for both proteins decreased with increasing doses of DXR, but this reduction was more clearly evident with cTnT than with cTnI. Thus, both cTnT and cTnI can be used to monitor damage to cardiac myocytes in DXR cardiomyopathy. - doxorubicin, cardiac toxicity, troponin-T, cardiac damage, cardiomyopathy, troponin-I

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005312-03
Application #
6290465
Study Section
Special Emphasis Panel (PA)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code