Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility
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 treatme...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2019.00332/full |
| _version_ | 1828862614108635136 |
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| author | Eduardo B. Carvalho Isalira P. R. Ramos Alvaro F. S. Nascimento Guilherme V. Brasil Debora B. Mello Martin Oti Michael Sammeth Maria T. Bahia Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Adriana B. Carvalho Adriana B. Carvalho Adriana B. Carvalho |
| author_facet | Eduardo B. Carvalho Isalira P. R. Ramos Alvaro F. S. Nascimento Guilherme V. Brasil Debora B. Mello Martin Oti Michael Sammeth Maria T. Bahia Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Adriana B. Carvalho Adriana B. Carvalho Adriana B. Carvalho |
| author_sort | Eduardo B. Carvalho |
| collection | DOAJ |
| description | 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 (ESV), end-diastolic volume (EDV), 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 (DCM) 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. |
| first_indexed | 2024-12-13T03:26:49Z |
| format | Article |
| id | doaj.art-bb871b42c5ed4488b874416d203a9e39 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T03:26:49Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-bb871b42c5ed4488b874416d203a9e392022-12-22T00:01:15ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882019-09-01910.3389/fcimb.2019.00332482364Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and ReproducibilityEduardo B. Carvalho0Isalira P. R. Ramos1Alvaro F. S. Nascimento2Guilherme V. Brasil3Debora B. Mello4Martin Oti5Michael Sammeth6Maria T. Bahia7Antonio C. Campos de Carvalho8Antonio C. Campos de Carvalho9Antonio C. Campos de Carvalho10Adriana B. Carvalho11Adriana B. Carvalho12Adriana B. Carvalho13Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilSchool of Medicine, Federal University of Ouro Preto, Ouro Preto, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilSchool of Medicine, Federal University of Ouro Preto, Ouro Preto, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Institute for Science and Technology in Regenerative Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilNational Institute for Science and Technology in Regenerative Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilBackground: 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 (ESV), end-diastolic volume (EDV), 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 (DCM) 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.https://www.frontiersin.org/article/10.3389/fcimb.2019.00332/fullChagas diseasechagasic cardiomyopathycanine modeldogssystolic dysfunction |
| spellingShingle | Eduardo B. Carvalho Isalira P. R. Ramos Alvaro F. S. Nascimento Guilherme V. Brasil Debora B. Mello Martin Oti Michael Sammeth Maria T. Bahia Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Antonio C. Campos de Carvalho Adriana B. Carvalho Adriana B. Carvalho Adriana B. Carvalho Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility Frontiers in Cellular and Infection Microbiology Chagas disease chagasic cardiomyopathy canine model dogs systolic dysfunction |
| title | Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility |
| title_full | Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility |
| title_fullStr | Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility |
| title_full_unstemmed | Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility |
| title_short | Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility |
| title_sort | echocardiographic measurements in a preclinical model of chronic chagasic cardiomyopathy in dogs validation and reproducibility |
| topic | Chagas disease chagasic cardiomyopathy canine model dogs systolic dysfunction |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2019.00332/full |
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