Cardioprotective and therapeutic effects of herbal extracts on isoproterenol-induced myocardial necrosis in rats

• Grant number: 13/05327-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2014
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Simone Gusmão Ramos
• Grantee: Simone Gusmão Ramos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Fabio Carmona

Abstract

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can evolve with heart failure (HF) and death. In a retrospective study of patients who underwent surgery for correction of congenital heart disease (CHD) with cardiopulmonary bypass (CPB) in HC FMRP-USP and evolved with death, we observed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. In the next study, we confirmed that after CPB there was a significant increase in gene expression of catecholamine receptor (²1 and ²2 adrenergic receptors) and receptor kinase GRK-2 in atrial cardiomyocytes compared with biopsies collected at the beginning of CPB. This alteration was associated with increased serum lactate, observed 12 h after the end of CPB. Moreover, the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and troponin I were also elevated after CPB and remained at high levels until 48 hours after surgery. These biochemical markers indicate some degree of tissue hypoxia / ischemia during the surgical procedure. With this finding, we suggest that the predominant myocardial injury in patients undergoing surgery for correction of CHD and CPB should be related to the release of catecholamines during surgery. Knowing the limitations of research involving human material we decided to reverse the process of translational medicine and study the effect of cardioprotective extracts in myocardial injuries by excessive circulating catecholamines. We will study the myocardium of rats, using a classical model of catecholamine induced-injury, isoproterenol (a synthetic catecholamine). In these hearts, we will evaluate two different mechanisms of action of isoproterenol: action on ²1 and ²2 adrenergic receptors and receptor kinase GRK-2 and oxidative stress production. In contrast, we will observe the interference of a purified plant extract, curcumin, considered as an effective cardioprotective in literature. This study has significant potential to address new targets to develop drugs that can prevent or treat myocardial damage, minimizing collateral effects of synthetic drugs. (AU)