Modulación del receptor Beta 1 adrenérgico sobre la función del neutrófilo en la recuperación del miocardio tras un evento de I/R

Abstract

Nowadays, cardiovascular diseases have a high incidence in the general population having special importance the acute myocardial infarction. During myocardial infarction, the obstruction of a coronary artery that irrigates the cardiac muscle occurs, thus causing stress, necrosis and damage to the infarcted area. This period when the blood cannot go through the vessels is named ischemia. The primary treatment for the restauration of the flow (reperfusion) are surgical techniques, meaning the blood flow is recovered and the heart is irrigated the novo, but also this reperfusion causes damage in the tissue and produce an inflammatory scenario. Studies of the group have shown that with the administration of metoprolol pre-reperfusion, a reduction of the infarct occurs due to a lower infiltration of the neutrophils in this area. Neutrophils produce a proinflammatory scene in the cardiac tissue due to the production of many inflammatory mediators such as metaloproteases, reactive oxygen species or proteases which degrades the extracellular matrix. On the other hand, some studies have shown a polarization of the neutrophils similarly to the macrophages one, these cells can be polarized towards an anti-inflammatory (N2) or proinflammatory (N1) phenotype. This polarization leads the neutrophil a specific regulation of the inflammatory environment. Several inflammatory mediators are present in this response, such as iNOS, MMP9, Il-1 beta, arginase 1, TGF beta, among others, which are involved in this inflammation or its resolution. In this study, we evaluate inflammatory mediators in three different groups, control, metoprolol-treated and neutrophil-depleted animals in order to test two different strategies for modifying neutrophil phenotypes impact on its 7 days post-infarct cardiac function. It was observed that with the application of metoprolol pre-reperfusion, a more severe anti-inflammatory phenotype is obtained compared to a proinflammatory one by the neutrophils that infiltrate the tissue. Through echocardiographic studies, it was determinate that this anti-inflammatory environment improves cardiac function 7 days post-infarction, being this evaluated by means of left ventricular ejection fraction and cardiac output. To the contrary, in the saline groups a proinflammatory environment is mainly obtained, related to a worse cardiac function at 7 days and a more important tissue damage. Lastly, neutrophil depletion studies were carried out so that the environment presented after tissue repopulation could be observed. As a conclusion, the application of metoprolol pre-reperfusion creates an anti-inflammatory environment in the tissue, thus improving the recovery of cardiac function 7 days post-infarction. On the contrary, similar results were obtained in depleted mice due to that metoprolol-like function, so that it would be interesting to study the inflammatory environment in total depletion mice until its sacrifice.