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Study of the myocardial sympathetic innervation disturbance and myocardial perfusion changes and their correlation with the progression of the left ventricular dysfunction in an experimental model of chronic Changes cardiomyopathy

Grant number: 11/03261-4
Support type:Regular Research Grants
Duration: June 01, 2011 - May 31, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Marcus Vinicius Simões
Grantee:Marcus Vinicius Simões
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers: Alexandre Baldini de Figueiredo ; Benedito Carlos Maciel ; João Santana da Silva ; Marcos Antonio Rossi

Abstract

The pathophysiology of the chronic Chagas cardiomiopathy (CCC) presents several unknown aspects. The main point is the recognition of the mechanisms involved in the genesis of the myocardial damage appearing only 2 to 3 decades after the acute phase of the disease. The central role of a low-grade relentless parasitism and the auto-immune aggression is clearly defined. However, several clinical and experimental studies suggest the contribution of other ancillary mechanisms: the extensive and early autonomic denervation and the microvascular ischemia. The definite evidence confirming the participation of these mechanisms in the progression of the myocardial disease demands a prospective longitudinal clinical study correlating the natural history of the disease with the changes in perfusion and innervation. However, this study is virtually impossible to be done in humans as the follow-up period would be excessively long, around 2 to 3 decades. In this scenario, it would be very useful the use of a hamster experimental model of CCC that reproduces myocardial dysfunction after 8 months of infection. This initiative could also be suitable to employ a specific device for small animal acquisition and processing of high resolution scintigraphy images, which was recently developed by our investigational group, named "mini-SPECT". At this way, the present study aimed at investigating the correlation of myocardial perfusion and innervation changes with the progression of left ventricular dysfunction by using in vivo imaging with the mini-SPECT in a model of CCC in hamsters. We will use female hamsters infected with Y strain of T. cruzi. Assessments of the left ventricular remodeling and systolic function, by using 2D-Echocardiogram, will be performed every 2 months after infection.. Myocardial perfusion with Sestamibi-99mTc, and myocardial regional innervation with MIBG-Iodine-123, will be performed 2, 6 and 10 months after infection. At the end of the study, the animals will be euthanized to obtain histological information that will be correlated with the in vivo results. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LEMOS DE OLIVEIRA, LUCIANO FONSECA; THACKERAY, JAMES T.; MARIN NETO, JOSE ANTONIO; DIAS ROMANO, MINNA MOREIRA; VIEIRA DE CARVALHO, EDUARDO ELIAS; MEJIA, JORGE; TANAKA, DENISE MAYUMI; DA SILVA, GRACE KELLY; ABDALLA, DOUGLAS REIS; MALAMUT, CARLOS; BENGEL, FRANK M.; HIGUCHI, MARIA DE LOURDES; SCHMIDT, ANDRE; CUNHA-NETO, EDECIO; SIMOES, MARCUS VINICIUS. Regional Myocardial Perfusion Disturbance in Experimental Chronic Chagas Cardiomyopathy. JOURNAL OF NUCLEAR MEDICINE, v. 59, n. 9, p. 1430-1436, SEP 1 2018. Web of Science Citations: 2.
LEMOS DE OLIVEIRA, LUCIANO FONSECA; DIAS ROMANO, MINNA MOREIRA; VIEIRA DE CARVALHO, EDUARDO ELIAS; CABEZA, JORGE MEJIA; SALGADO, HELIO CESAR; FAZAN JUNIOR, RUBENS; COSTA, RENATA SESTI; DA SILVA, JOAO SANTANA; HIGUCHI, MARIA DE LOURDES; MACIEL, BENEDITO CARLOS; CUNHA-NETO, EDECIO; MARIN-NETO, JOSE ANTONIO; SIMOES, MARCUS VINICIUS. Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy. JOURNAL OF THE AMERICAN HEART ASSOCIATION, v. 5, n. 1 JAN 2016. Web of Science Citations: 5.
LEMOS DE OLIVEIRA, LUCIANO FONSECA; MEJIA, JORGE; VIEIRA DE CARVALHO, EDUARDO ELIAS; LATARO, RENATA MARIA; FRASSETTO, SARITA NASBINE; FAZAN, JR., RUBENS; SALGADO, HELIO CESAR; GALVIS-ALONSO, ORFA YINETH; SIMOES, MARCUS VINICIUS. Myocardial Infarction Area Quantification using High-Resolution SPECT Images in Rats. Arquivos Brasileiros de Cardiologia, v. 101, n. 1, p. 59-67, JUL 2013. Web of Science Citations: 7.

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