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Study of the effects of a coronary microcirculation vasodilator drug on the myocardial perfusion and left ventricular dysfunction in a model of chronic chagas cardiomyopathy in hamsters

Grant number: 14/07722-4
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2014
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Marcus Vinicius Simões
Grantee:Denise Mayumi Tanaka
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Microvascular ischemia is supposed to take part in the pathophysiological mechanism that generates the chronic myocardial damage in Chagas's Cardiomyopathy (CCC). Transient myocardial hypoperfusion may contribute for the development of regional and global left ventricular systolic dysfunction through a mechanism of myocardial hibernation and subsequent appearance of regional fibrosis. Its conceivable to hypothesize that a coronary vasodilator agent used as therapeutic intervention to reduce the myocardial ischemia phenomena could improve ventricular function and reduce the progression of myocardial damage in CCC. Thus, this study aimed at assessing the effects of dipyridamole (DIPI) on myocardial perfusion and left ventricular systolic function using in vivo imaging, and correlating these findings with histopathological changes in hamsters chronically infected with T cruzi. The CCC will be produced by inoculation of 3.5 x 100000 trypomastigotes of T. cruzi Y strain. Six months after the infection the animals will be distributed in 4 experimental groups: 1. Chagas Disease + DIPI (n=15); 2. Chagas Disease + placebo (n=15); 3. Control + DIPI (n=15); 4. Control + placebo (n=15). The animals will be evaluated by using doppler echocardiography and myocardial perfusion scintigraphy, followed by drug therapy with dipyridamole (4mg/Kg) by i.p injection, twice a day or placebo (equal volume of saline soluction), for 4 weeks. After treatment, the animals will be evaluated by the same imaging methods and sacrificed afterwards for heart tissue hystopathologic analysis. (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)
TANAKA, DENISE MAYUMI; LEMOS DE OLIVEIRA, LUCIANO FONSECA; MARIN-NETO, JOSE ANTONIO; DIAS ROMANO, MINNA MOREIRA; VIEIRA DE CARVALHO, EDUARDO ELIAS; LEITE DE BARROS FILHO, ANTONIO CARLOS; FRANCA RIBEIRO, FERNANDO FONSECA; CABEZA, JORGE MEJIA; LOPES, CARLA DUQUE; FABRICIO, CAMILA GODOY; KESPER, NORIVAL; MOREIRA, HENRIQUE TURIN; WICHERT-ANA, LAURO; SCHMIDT, ANDRE; HIGUCHI, MARIA DE LOURDES; CUNHA-NETO, EDECIO; SIMOES, MARCUS VINICIUS. Prolonged dipyridamole administration reduces myocardial perfusion defects in experimental chronic Chagas cardiomyopathy. JOURNAL OF NUCLEAR CARDIOLOGY, v. 26, n. 5, p. 1569-1579, OCT 2019. Web of Science Citations: 1.
TANAKA, D. M.; ROMANO, M. M. D.; CARVALHO, E. E. V.; OLIVEIRA, L. F. L.; SOUZA, H. C. D.; MACIEL, B. C.; SALGADO, H. C.; FAZAN-JUNIOR, R.; SIMOES, M. V. Effect of different anesthetic agents on left ventricular systolic function assessed by echocardiography in hamsters. Brazilian Journal of Medical and Biological Research, v. 49, n. 10 2016. Web of Science Citations: 2.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TANAKA, Denise Mayumi. Study of the effect of a vasodilating agent of the coronary microcirculation on myocardial perfusion disorders and left ventricular dysfunction in a hamster model of chronic chagasic cardiomyopathy. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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