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Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits
Authors:Michaela Adamcová  Vladimír Geršl  Radomír Hrdina  Milan Mělka  Yvona Mazurová  Jaroslava Vávrová  Vladimír Palička  Zdeněk Kokštein
Affiliation:(1) Department of Physiology, Charles University Faculty of Medicine in Hradec Králové, Šimkova 870, 500 01 Hradec Králové, Czech Republic e-mail: adamcova@lfhk.cuni.cz Tel.: +420-49-5816180 Fax: +420-49-33365,;(2) Department of Pharmacology, Charles University Faculty of Medicine in Hradec Králové, Czech Republic,;(3) Department of Pharmacology and Toxicology, Charles University Faculty of Pharmacy in Hradec Králové, Czech Republic,;(4) Department of Biochemistry, Charles University Faculty of Medicine in Hradec Králové, Czech Republic,;(5) Department of Histology, Charles University Faculty of Medicine in Hradec Králové, Czech Republic,;(6) Institute of Clinical Biochemistry and Diagnosis, Teaching Hospital, Hradec Králové, Czech Republic,;(7) Department of Pediatrics, Teaching Hospital, Hradec Králové, Czech Republic,
Abstract: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 μg/1) 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 μg/l) correlated with their premature death. In the control group, the levels of cTnT were always lower than 0.1 μg/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. Received: 1 October 1998 / Accepted: 23 November 1998
Keywords:Cardiac troponin T  Daunorubicin  Oracin  Cardiomyopathy  Rabbits
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