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Study of therapeutic and cardioprotective effect of herbal extracts on isoproterenol-induced myocardial necrosis in rats

Grant number: 13/18392-2
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): December 01, 2013
Effective date (End): November 30, 2014
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Simone Gusmão Ramos
Grantee:Marcela Silva de Oliveira
Supervisor abroad: William T. Pu
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Harvard University, Boston, United States  
Associated to the scholarship:13/05347-9 - Study of the therapeutic and cardioprotective effects of herbal extracts on isoproterenol-induced myocardial necrosis in rats., BP.PD


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 pro-B-type 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. Considering the limitations of research involving human material we decided to reverse the process of translational medicine and study the myocardium of rats, using a classical model of catecholamine induced-injury, isoproterenol (a synthetic catecholamine) and observe the interference of a purified plant extract, curcumin, considered as an effective cardioprotective in literature. The internship abroad under Prof. Pu´s supervisor has as main aim to provide skills in neonatal cardiomyocyte isolation, culture and immunofluorescence techniques of cultured cardiomyocytes for posteriorly contribute to research project developed in the country. Furthermore new technologies in molecular cardiology used in the laboratory abroad will also be acquired. The knowledge and "tips" acquired during the training will be disseminated and utilized by our staff in Brazil and who else might be interested. (AU)

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