2026, Number 2
Cardiovasc Metab Sci 2026; 37 (2)
A comparative evaluation of sacubitril-valsartan and nebivolol-valsartan in left ventricular remodeling following chronic myocardial infarction in female Wistar rats
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 resulted in six experimental groups. There was a reduction in the mortality rate, reduction of hypertrophy and cardiac fibrosis when the NV combination was administered seven days after ligation. In conclusion, sacubitril–valsartan appears to be a safe and effective strategy to attenuate cardiac and pulmonary fibrosis after infarction female rats, however, based on the results, early administration of nebivolol-valsartan is not recommended, as it appears to increase the risk of post-infarction complications.