Inflamação miocárdica: papel da dexametasona e do ramipril no remodelamento cardíaco de ratos com insuficiência cardíaca

Abstract

Cardiac inflammation has been considered an important mechanism involved in heart failure (HF). Anti-inflammatories, such as dexamethasone (DEX), could be used to control cardiac inflammation, while that angiotensin-converting enzyme inhibitors have been shown to improve survival for regressing cardiac remodeling in HF. Thus, this work aimed to evaluate the effects of DEX treatment or ramipril treatment on inflammation and cardiac remodeling. Wistar rats were submitted to an aortic stenosis (AS) protocol. After 21 weeks, an echocardiogram was performed and, after 24 weeks of surgery, animals were treated with DEX (50μg/kg, s.c.), ramipril (10mg/kg, via gavage) or saline. After treatment, all rats were submitted to an echocardiogram and, at the end of experimental protocol, the groups were euthanized, and left ventricle was removed for analysis of cytokines and inflammatory markers, as well as histological analyzes. The results showed that the animals with AS had an increase in the relative thickness of the left ventricle (+63%), while the treatment with DEX attenuated this increase (-17%) and treatment with ramipril did not promote any change. Although the AS surgery promoted an increase in fibrosis in the heart (+70%), only the DEX treatment attenuated this increase significantly (-23%). This cardiac remodeling promoted worsening of cardiac function that was not readjusted with the improvement of cardiac remodeling with both treatments. The improvement in cardiac remodeling in the treatment with DEX may be related to the improvement in the inflammatory profile in the treatment, as there was a reduction in the cytokines and inflammatory markers that were increased with AS. Although treatment with ramipril did not promote any significant changes in cardiac remodeling, it is already possible to observe an attenuation of the cardiac inflammatory profile in these animals. In conclusion, the present study suggests that DEX may be beneficial in mitigating the progression of heart disease due to an attenuation of cardiac remodeling induced by lower cardiac inflammation. In addition, although treatment with ramipril attenuated cardiac inflammation, it did not significantly improve cardiac remodeling or function, suggesting that longer periods of ramipril treatment could be used.