title: Comparison of cardiac troponin I and T, including the evaluation of an ultrasensitive assay, as indicators of doxorubicin-induced cardiotoxicity.
abstract: Cardiac troponin (cTn) has been utilized to assess acute myocardial injury, but the cTn response in active/ongoing chronic injury is not well documented. The purpose of this study was to characterize the cardiac troponin I (cTnI), cardiac troponin T (cTnT), high-sensitivity cTnI, hematology, and clinical chemistry responses in rats treated with doxorubicin. Rats treated with 1, 2, or 3 mg/kg/week (wk) of doxorubicin for 2, 4, or 6 wks were sacrificed after 0, 2, or 4 wks of recovery and compared to untreated controls and animals treated with doxorubicin/dexrazoxane (50 mg/kg/wk) or etoposide (1 and 3 mg/kg/wk). The incidence and mean magnitude of cTn response increased with increasing dose and/or duration of doxorubicin treatment. Conversely, dexrazoxane/doxorubicin was partially protective for cardiotoxicity, and minimal cardiotoxicity occurred with etoposide treatment. Both cTnI and cTnT effectively identified doxorubicin-induced injury as indicated by vacuolation of cardiomyocytes of the atria/ventricles. The association between the cTn responses and histological changes was greater at the higher total exposures, but the magnitude of cTn response did not match closely with histologic grade. The high-sensitivity cTnI assay was also effective in identifying cardiac injury. Alterations occurred in the hematology and clinical chemistry parameters and reflected both dose and duration of doxorubicin treatment.
authors.affiliation: 1Pfizer Global Research Development, Groton, Connecticut, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Reagan
authors.forename: Malcolm
authors.initials: M
authors.lastname: York
authors.forename: Brian
authors.initials: B
authors.lastname: Berridge
authors.forename: Eric
authors.initials: E
authors.lastname: Schultze
authors.forename: Dana
authors.initials: D
authors.lastname: Walker
authors.forename: Syril
authors.initials: S
authors.lastname: Pettit
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019963:Clinical Chemistry Tests; D004317:Doxorubicin / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000097:blood* / Q000139:chemically induced* / Q000378:metabolism; D006403:Hematologic Tests; D008297:Male; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D018675:Toxicity Tests; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D019210:Troponin I; D020107:Troponin T; D004317:Doxorubicin
keywords: cardiac troponin; cardiovascular system; clinical pathology; doxorubicin.; rat