Fig. 1

Translational concept and in vivo study protocol. On the upper timeline, cardiac deterioration, symptom development and clinical management of a hypothetical oncological patient suffering from DOX-induced cardiotoxicity can be seen, who was diagnosed with heart failure at an advanced stage resulting in a poor prognosis. On the lower timeline, the in vivo study protocol of the animals can be seen based on a translational concept. Following baseline blood pressure, heart rate measurements and echocardiography, animals in the PRE group received a daily combination of gradually uptitrated oral bisoprolol, perindopril and eplerenone started a week before DOX, while those in the POST group had the same therapy started 1 month after the intravenous DOX treatment. According to our concept, the PRE treatment represents a prophylactic cardioprotective approach for healthy subjects, which measure is currently missing from human practice, while the POST group represents subjects diagnosed with heart failure already at an advanced stage, where supportive therapy is ineffective. Animals in the CON and D-CON groups received a drug-free vehicle (“placebo”) orally throughout the study, while those in the POST group had it until day 51, then the drug-free vehicle was switched to an active heart failure therapy. The intravenous DOX exposure was carried out on days 8, 11, 14, 17, 20 and 23 in the D-CON, PRE and POST groups, while animals in the CON group received intravenous saline on the same days. Follow-up blood pressure and heart rate measurements were performed on days 7 and 39, while follow-up echocardiography was carried out on days 51 and 80. AA aldosterone antagonist (eplerenone), ACEI angiotensin converting enzyme inhibitor (perindopril), BB β-blocker (bisoprolol), DOX doxorubicin, Echo echocardiography, HF heart failure, LV left ventricular