Primary prevention of chronic anthracycline cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane in post-treatment follow-up.
Clin Sci (Lond)
; 136(1): 139-161, 2022 01 14.
Article
en En
| MEDLINE
| ID: mdl-34878093
Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline (ANT)-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent ANT-induced cardiac damage and provide long-lasting cardioprotection. The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II ß (TOP2B)-dependent DNA damage responses in the heart.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de la Enzima Convertidora de Angiotensina
/
Daunorrubicina
/
Perindopril
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Cardiotoxicidad
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Sci (Lond)
Año:
2022
Tipo del documento:
Article
País de afiliación:
República Checa
Pais de publicación:
Reino Unido