Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits.
Anthracycline derivatives are among the most effective antineoplastic drugs but their therapeutic use is limited by their adverse effects. The cardiac side-effects of antineoplastic drugs were investigated in rabbits in vivo from the viewpoint of release of cardiac troponin T (cTnT) measured by Elecsys Troponin T STAT immunoassay (Boehringer Mannheim, Germany). No increase in cTnT was found following administration of a single dose of daunorubicin (3 mg/kg i.v., n = 4). During development of daunorubicin-induced cardiomyopathy (daunorubicin 3 mg/kg i.v., once a week; maximum nine administrations, n = 7), the levels of cTnT were within the physiological range (i.e. cTnT <0.1 microg/l) at the beginning of the experiment and before and after the 5th administration, but the pathological values of cTnT after the 8th administration in 43% animals (0.22+/-0.08 microg/l) correlated with their premature death. In the control group, the levels of cTnT were always lower than 0.1 microg/l during the experiment. Following administration of a new antineoplastic drug - Oracin [6-[2-(2-hydroxyethyl) aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno [1,2-c]-isoquinoline hydrochloride, 10 mg/kg i.v., once weekly, ten administrations, n = 7], there was no increase in cTnT levels. These findings correlated with the PEP: LVET index, histological examination and no animal succumbing to premature death. It is possible to conclude that cTnT is a useful marker for the prediction of experimentally induced anthracycline cardiomyopathy and for the evaluation of cardiotoxic (and, possibly, cardioprotective) effects of new drugs in rabbits.
Adamcová
M
M
Department of Physiology, Charles University Faculty of Medicine in Hradec Králové, Czech Republic. adamcova@lfhk.cuni.cz
Gersl
V
V
Hrdina
R
R
Melka
M
M
Mazurová
Y
Y
Vávrová
J
J
Palicka
V
V
Kokstein
Z
Z
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000378:metabolism*; D003630:Daunorubicin / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000009:adverse effects*; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D020107:Troponin T / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D015415:Biomarkers; D004983:Ethanolamines; D007546:Isoquinolines; D020107:Troponin T; C103439:oracine; D003630:Daunorubicin