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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00332

Echocardiographic measurements in a preclinical model of chronic chagasic cardiomyopathy in dogs: validation and reproducibility

Eduardo B. Carvalho1,  Isalira P. Ramos1, Alvaro S. Nascimento2,  GUILHERME V. BRASIL1,  Debora B. Mello1, Martin Oti1, Michael Sammeth1, Maria T. Bahia2,  Antonio C. Campos De Carvalho1 and  Adriana Bastos Carvalho1*
  • 1Federal University of Rio de Janeiro, Brazil
  • 2Universidade Federal de Ouro Preto, Brazil

Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi.
Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume, end-diastolic volume, ejection fraction (EF) and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ≤ 40%, established for dilated cardiomyopathy in dogs, only 28% of the infected dogs were affected by the chronic infection.
Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function.

Keywords: Chagas Disease, Chagasic cardiomiopathy, canine model, Dogs, systolic dysfunction

Received: 01 Jul 2019; Accepted: 10 Sep 2019.

Copyright: © 2019 Carvalho, Ramos, Nascimento, BRASIL, Mello, Oti, Sammeth, Bahia, Campos De Carvalho and Bastos Carvalho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Adriana Bastos Carvalho, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-901, Rio de Janeiro, Brazil, carvalhoab@biof.ufrj.br