Pérez-García, Erika; Valencia-Hernández, Ignacio; Lezama-Martínez, Diego; Ramírez-Hernández, Diana; Garrido-Fariña, Germán Isauro; Ramírez-Hernández, César; Reyes-Alvarado, Karla; Hidalgo, Isabel; Flores-Monroy, Jazmín

ABSTRACT

Cardiac fibrosis following a myocardial infarction (MI) leads to adverse left ventricular remodeling and heart failure, with distinct patterns observed in women. Despite having smaller infarcts and less profibrotic activity, women have a higher risk of post-MI mortality and heart failure. Since on therapies currently target fibrosis directly, studying these mechanisms is essential for developing and testing treatments, including approved heart failure drugs such as sacubitril–valsartan. This study aimed to compare and evaluate the combination of nebivolol-valsartan (NV) vs sacubitril-valsartan (SV) as a known treatment for chronic infarction in female rats; 26-weeks-old Wistar rats were used. The animals were divided into four groups (n = 6): 1) control (SHAM); 2) myocardial infarction (LADL); 3) LADL + sacubitril 30 mg/kg/day + valsartan 28 mg/kg/day (LADL + SV); 4) LADL + valsartan 30 mg/kg/day + nebivolol 5 mg/kg/day (LADL + NV). Infarct induction was performed by permanent ligation of the left anterior descending coronary artery. The treated groups received their treatments right after infarct induction for two weeks. The rats were euthanized by cervical dislocation and hearts and lungs were obtained from all groups for histology using Van Gieson and HE staining. The NV combination resulted in 50% mortality in animals, promoting pulmonary congestion and pleural effusion. Therefore, the administration of the NV combination at different times was proposed, after three and seven days post-infarction. This NV provocó una mortalidad de 50% en los animales, lo que favoreció la congestión pulmonar y el derrame pleural. Por lo tanto, se propuso la administración de la combinación de NV en diferentes momentos, a los tres y a los siete días tras el infarto. Esto dio lugar a seis grupos experimentales. Se observó una reducción de la tasa de mortalidad, así como de la hipertrofia y la fibrosis cardiaca, cuando la combinación de NV se administró siete días después de la ligadura. En conclusión, el sacubitril-valsartán parece ser una estrategia segura y eficaz para atenuar la fibrosis cardiaca y pulmonar tras el infarto en ratas hembras, mientras que la administración temprana de nebivolol-valsartán no se recomendaría de acuerdo a los resultados, ya que aparentemente podría generar más complicaciones postinfarto.

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