A new therapeutic approach in cardiology: treatment of acute myocardial infarction with methotrexate associated with lipid nanoemulsions

Abstract

Acute Myocardial Infarction (AMI), the main death cause in the Western world and in Brazil, is accompanied by cardiac remodeling that frequently results in cardiac failure. The inflammatory process that occurs in AMI is the main causal fator of cardiac remodeling. The aim is to investigate the effects of metothrexate (MTX), an imunossupressor and anti-proliferative agent, on the model of AMI induced in the rat. MTX will be test both as the free compound or associated to a lipid nanoemulsion (LDE). Studies from our laboratory showed that LDE use as drug vehicle has the ability to concentrate the chemotherapeutic agents in the inflammation sites and decreases the high toxicity of those agents. Male Wistar rats submitted to the coronary occlusion and a Sham group of animals will be observed during 6 weeks. Echocardiography will be performed within 24 h after the surgery and after a 6-week follow-up, when the animals will be sacrificed. Blood samples will be collected for determination of blood count, lipid profile and plasma interleukins. Immunohistological, biochemical and molecular biology assays will be performed in fragments of the left ventricle, at the infarcted and remote regions to the infarction. Those assays will evaluate changes in structure and function of the left ventricle, cell death, inflammatory process, myocardial fibrosis, expression and activity of metaloproteinases, as well the oxidative stress and gene and protein expression. Our work hypothesis was confirmed by results of a pilot-study that showed that MTX associated to LDE improved the post-AMI cardiac function, as evaluated by echocardiography. Eventual beneficial effects from the treatment of MTX associated to LDE have the potencial of promoting a revolution in the clinical management of post-AMI patients. (AU)