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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2020

01-12-2020 | Bisoprolol | Research

Prophylactic, single-drug cardioprotection in a comparative, experimental study of doxorubicin-induced cardiomyopathy

Authors: Mária Lódi, Viktor Bánhegyi, Beáta Bódi, Alexandra Gyöngyösi, Árpád Kovács, Anita Árokszállási, Nazha Hamdani, Miklós Fagyas, István Édes, Zoltán Csanádi, István Czuriga, Zoltán Kisvárday, István Lekli, Péter Bai, Attila Tóth, Zoltán Papp, Dániel Czuriga

Published in: Journal of Translational Medicine | Issue 1/2020

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Abstract

Background

Cardiomyopathy is a common side effect of doxorubicin (DOX) chemotherapy. Despite intensive research efforts in the field, there is still no evidence available for routine cardioprotective prophylaxis to prevent cardiotoxicity in the majority of oncological patients at low risk of cardiovascular disease. We have recently demonstrated the advantages of a prophylactic, combined heart failure therapy in an experimental model of DOX-induced cardiomyopathy. In the current work, we focus on individually applied prophylactic medications studied in the same translational environment to clarify their distinct roles in the prevention of DOX cardiotoxicity.

Methods

Twelve-week-old male Wistar rats were divided into 5 subgroups. Prophylactic β-blocker (BB, bisoprolol), angiotensin-converting enzyme inhibitor (ACEI, perindopril) or aldosterone antagonist (AA, eplerenone) treatments were applied 1 week before DOX administration, then 6 cycles of intravenous DOX chemotherapy were administered. Rats receiving only intravenous DOX or saline served as positive and negative controls. Blood pressure, heart rate, body weight, and echocardiographic parameters were monitored in vivo. Two months after the last DOX administration, the animals were sacrificed, and their heart and serum samples were frozen in liquid nitrogen for histological, mechanical, and biochemical measurements.

Results

All prophylactic treatments increased the survival of DOX-receiving animals. The lowest mortality rates were seen in the BB and ACEI groups. The left ventricular ejection fraction was only preserved in the BB group. The DOX-induced increase in the isovolumetric relaxation time could not be prevented by any prophylactic treatment. A decreased number of apoptotic nuclei and a preserved myocardial ultrastructure were found in all groups receiving prophylactic cardioprotection, while the DOX-induced fibrotic remodelling and the increase in caspase-3 levels could only be substantially prevented by the BB and ACEI treatments.

Conclusion

Primary prophylaxis with cardioprotective agents like BB or ACEI has a key role in the prevention of DOX-induced cardiotoxicity in healthy rats. Future human studies are necessary to implement this finding in the clinical management of oncological patients free of cardiovascular risk factors.
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Metadata
Title
Prophylactic, single-drug cardioprotection in a comparative, experimental study of doxorubicin-induced cardiomyopathy
Authors
Mária Lódi
Viktor Bánhegyi
Beáta Bódi
Alexandra Gyöngyösi
Árpád Kovács
Anita Árokszállási
Nazha Hamdani
Miklós Fagyas
István Édes
Zoltán Csanádi
István Czuriga
Zoltán Kisvárday
István Lekli
Péter Bai
Attila Tóth
Zoltán Papp
Dániel Czuriga
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02564-w

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