Early detection of anthracycline cardiotoxicity in a rabbit model: left ventricle filling pattern versus troponin T determination

Abstract

Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt(min) index obtained invasively at the end of the study revealed a significant impairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model.

Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model

“…The first analysis was done after five weekly DAU cycles (cumulative dose ∼ 250 mg/m 2 ) when the first signs of the chronic cardiotoxicity, i.e., significantly increased levels of plasma cTnT, have been previously found, but without any significant concomitant change in systolic function as determined by non-invasive examinations ( Sterba et al, 2007 ; Jirkovský et al, 2013 ; Adamcova et al, 2015 ). The second analysis was performed after ten weekly DAU cycles (cumulative dose ∼ 500 mg/m 2 ), which is known from previous studies to induce significant LV systolic dysfunction and all the typical histopathological hallmarks of chronic ANT cardiotoxicity ( Šimůnek et al, 2003 ).…”