Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica

Detalhes bibliográficos
Autor(a) principal: Thayrine Rosa Damasceno
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/55370
https://orcid.org/0000-0002-3442-9193
Resumo: Chronic Chagas cardiomyopathy (CCC) is the most severe form of non-ischemic cardiomyopathy in Latin America. The persistent and low-intensity infection by Trypanosoma cruzi triggers a complex and long-lasting pathogenesis leading to the development of parasite-dependent myocardial damage, immune-mediated myocardial injury, microvascular disorders and cardiac dysautonomia, which contribute to the progression of ventricular dysfunction and reduction in cardiorespiratory fitness (CRF). Few studies suggest that aerobic physical training (APT) can lead to improvement in CRF and myocardial damage. The objectives of this study were to evaluate the effects of APT on myocardial morphology, function and perfusion and correlate these variables with inflammation and fibrosis in an experimental model of CCC using high-resolution in vivo images. Additionally, to investigate the influence of these alterations in the reduction of CRF. Furthermore, as a secondary objective, to analyze the cross-sectional areas of the skeletal muscle. In order to verify the clinical application of the study, we also performed a retrospective analysis of patients with CCC. Female Syrian hamsters with CCC and their controls (CT) were allocated into four groups: CCC-APT (n=22), CCC-SED (n=22), CT-APT (n=8) and CT-SED (n= 8). Seven months after infection, the animals were submitted to two-dimensional echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. The training was carried out for eight weeks, five times a week, for fifty minutes. After completing the APT protocol, the animals were reassessed, euthanized and cardiac tissue samples were collected for histopathological analysis. In the retrospective clinical analysis, four patients with CCC performed aerobic exercise at moderate to high intensity (60 to 85% of VO2peak) for twelve weeks. In the baseline evaluation, before allocation to the groups, chagasic animals showed similar peak oxygen consumption (VO2peak) (p>0.05), increased areas of myocardial perfusion defect (MPD) [4.5(2.7-8.5) vs 2.6(0.8-3.9), p=0.014] and reduction in left ventricular ejection fraction (LVEF) [46.9(40.3 -49 .7) vs 51.7 (49.4-53.3), p < 0.001] when compared to control animals. The correlation analysis showed that VO2peak correlated with MPD (r=-660; p<0.0001), LVEF (r=0.374; p=0.022), LVDD (r=-0.533; p=0.001) and LVSD (r=-0.49; p=0.001). Only MPD remained independently associated with VO2peak (adjusted r²=0.42). After animals allocation, mixed ANOVA showed reduced LVEF in chagasic groups [CCC-SED 46.72 (40.01-51.06)%] and CCC-APT [46.87 (42.35-50.10)%; p=0.015] when compared with CT-SED [53.06 (51.95-54.00)%, pANOVA=0.009]. After APT, mixed ANOVA identified reduced LVEF, significant increase in MPD over time, and more inflammation [(1.60±0.63); pANOVA<0.0001] and type 1 collagen [1.84 (1.22-2.82); pANOVA=0.008] in the CCC-SED group, when compared to the other groups. On the other hand, APT in the CCC-APT group reduced inflammation [(0.93±0.20); pANOVA<0.0001], prevented the progression of MPD and myocardial fibrosis, attenuated left ventricular dysfunction and improved the CRF. In animals with CCC, APT reduced inflammation, prevented the progression of MPD and fibrosis, attenuated left ventricular remodeling, improved functional capacity and promoted musculoskeletal structural recovery, reducing muscle atrophy. Furthermore, in patients with CCC, APT decreased MPD, improved LVEF and CRF.
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spelling Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônicaCardiomiopatia chagásicaMiocarditeCapacidade funcionalExercício aeróbicoInflamaçãoImagiologia de perfusão miocárdicaDoenças cardiovascularesChagas, Doença deReabilitaçãoCapacidade funcionalExercícios físicosChronic Chagas cardiomyopathy (CCC) is the most severe form of non-ischemic cardiomyopathy in Latin America. The persistent and low-intensity infection by Trypanosoma cruzi triggers a complex and long-lasting pathogenesis leading to the development of parasite-dependent myocardial damage, immune-mediated myocardial injury, microvascular disorders and cardiac dysautonomia, which contribute to the progression of ventricular dysfunction and reduction in cardiorespiratory fitness (CRF). Few studies suggest that aerobic physical training (APT) can lead to improvement in CRF and myocardial damage. The objectives of this study were to evaluate the effects of APT on myocardial morphology, function and perfusion and correlate these variables with inflammation and fibrosis in an experimental model of CCC using high-resolution in vivo images. Additionally, to investigate the influence of these alterations in the reduction of CRF. Furthermore, as a secondary objective, to analyze the cross-sectional areas of the skeletal muscle. In order to verify the clinical application of the study, we also performed a retrospective analysis of patients with CCC. Female Syrian hamsters with CCC and their controls (CT) were allocated into four groups: CCC-APT (n=22), CCC-SED (n=22), CT-APT (n=8) and CT-SED (n= 8). Seven months after infection, the animals were submitted to two-dimensional echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. The training was carried out for eight weeks, five times a week, for fifty minutes. After completing the APT protocol, the animals were reassessed, euthanized and cardiac tissue samples were collected for histopathological analysis. In the retrospective clinical analysis, four patients with CCC performed aerobic exercise at moderate to high intensity (60 to 85% of VO2peak) for twelve weeks. In the baseline evaluation, before allocation to the groups, chagasic animals showed similar peak oxygen consumption (VO2peak) (p>0.05), increased areas of myocardial perfusion defect (MPD) [4.5(2.7-8.5) vs 2.6(0.8-3.9), p=0.014] and reduction in left ventricular ejection fraction (LVEF) [46.9(40.3 -49 .7) vs 51.7 (49.4-53.3), p < 0.001] when compared to control animals. The correlation analysis showed that VO2peak correlated with MPD (r=-660; p<0.0001), LVEF (r=0.374; p=0.022), LVDD (r=-0.533; p=0.001) and LVSD (r=-0.49; p=0.001). Only MPD remained independently associated with VO2peak (adjusted r²=0.42). After animals allocation, mixed ANOVA showed reduced LVEF in chagasic groups [CCC-SED 46.72 (40.01-51.06)%] and CCC-APT [46.87 (42.35-50.10)%; p=0.015] when compared with CT-SED [53.06 (51.95-54.00)%, pANOVA=0.009]. After APT, mixed ANOVA identified reduced LVEF, significant increase in MPD over time, and more inflammation [(1.60±0.63); pANOVA<0.0001] and type 1 collagen [1.84 (1.22-2.82); pANOVA=0.008] in the CCC-SED group, when compared to the other groups. On the other hand, APT in the CCC-APT group reduced inflammation [(0.93±0.20); pANOVA<0.0001], prevented the progression of MPD and myocardial fibrosis, attenuated left ventricular dysfunction and improved the CRF. In animals with CCC, APT reduced inflammation, prevented the progression of MPD and fibrosis, attenuated left ventricular remodeling, improved functional capacity and promoted musculoskeletal structural recovery, reducing muscle atrophy. Furthermore, in patients with CCC, APT decreased MPD, improved LVEF and CRF.A cardiomiopatia chagásica crônica (CCC) é a forma mais grave de cardiomiopatia não isquêmica na América Latina. A infecção persistente e de baixa intensidade pelo Trypanosoma cruzi desencadeia uma fisiopatogenia complexa e de longa duração levando ao desenvolvimento de dano miocárdico parasita-dependente, lesão miocárdica imunomediada, distúrbios microvasculares e disautonomia cardíaca, que contribuem para a progressão da disfunção ventricular e redução da capacidade funcional. Poucos estudos sugerem que o treinamento físico aeróbico (TFA) possa levar a melhora da capacidade funcional e do dano miocárdico. Os objetivos do estudo foram avaliar os efeitos do TFA na morfologia, função e perfusão miocárdica e correlacionar essas variáveis com inflamação e fibrose em modelo experimental de CCC usando imagens de alta resolução in vivo. Adicionalmente, investigar a influência dessas alterações na redução da capacidade funcional. Ademais, como objetivo secundário, analisar as áreas de secção transversa do músculo esquelético. A fim de verificar a aplicação clínica do estudo, também realizar uma análise retrospectiva de pacientes com CCC. Hamsters sírios fêmeas com CCC e seus controles (CT) foram alocados em quatro grupos: CCC-TFA (n=22), CCC-SED (n=22), CT-TFA (n=8) e CT-SED (n=8). Sete meses após a infecção, os animais foram submetidos aos exames de ecocardiograma bidimensional, cintilografia de perfusão miocárdica e teste de esforço cardiopulmonar. O treinamento foi realizado por oito semanas, cinco vezes por semana, durante cinquenta minutos. Após finalizarem o protocolo de TFA, os animais foram reavaliados, eutanasiados e amostras de tecido cardíaco foram coletadas para análise histopatológica. Na análise clínica retrospectiva, quatro pacientes com CCC realizaram exercício aeróbico em intensidade moderada a alta (60 a 85% do VO2pico) por doze semanas. Na avaliação basal, antes da alocação nos grupos, animais chagásicos apresentaram consumo de oxigênio pico (VO2pico) semelhantes (p>0,05), aumento das áreas de defeito de perfusão miocárdica (DPM) [4,5(2,7-8,5) vs 2,6(0,8-3,9), p=0,014] e redução da fração de ejeção do ventrículo esquerdo (FEVE) [46,9(40,3-49,7) vs 51,7 (49,4-53,3), p<0,001] em comparação com animais controles. A análise de correlação mostrou que o VO2pico correlacionou-se com o DPM (r=-660; p<0,0001), FEVE (r=0,374; p=0,020), DDVE (r=-0,533; p=0,001) e DSVE (r=-0,480; p=0,001). Somente o DPM permaneceu independentemente associado ao VO2pico (r²ajustado=0,42). Posteriormente a alocação dos animais, a ANOVA mista mostrou FEVE reduzida nos grupos chagásicos CCC-SED [46,72 (40,01-51,06)%] e CCC-APT [46,87 (42,35-50,10)%; p=0,015] quando comparados com o CT-SED [53,06 (51,95-54,00)%, pANOVA=0,009]. Após o TFA, a ANOVA mista identificou FEVE reduzida, significativo aumento dos DPM ao longo do tempo e mais inflamação [(1,60±0,63); pANOVA<0,0001] e colágeno tipo 1 [1,84 (1,22-2,82); pANOVA=0,008] no grupo CCC-SED, quando comparado aos outros grupos. Por outro lado, o TFA no grupo CCC-TFA reduziu inflamação [(0,93±0,20); pANOVA<0,0001], impediu a progressão dos DPM e fibrose miocárdica, atenuou a disfunção ventricular esquerda e melhorou a capacidade funcional. Em animais com CCC o TFA reduziu inflamação, impediu a progressão de DPM e fibrose, atenuou o remodelamento do ventrículo esquerdo, melhorou a capacidade funcional e promoveu a recuperação estrutural musculoesquelética, reduzindo a atrofia muscular. Ademais, em pacientes com CCC o TFA diminuiu o DPM, melhorou a FEVE e a capacidade funcional.FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPESP - Fundação de Amparo à Pesquisa do Estado de São PauloUniversidade Federal de Minas GeraisBrasilEEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONALPrograma de Pós-Graduação em Ciências da ReabilitaçãoUFMGLuciano Fonseca Lemos de Oliveirahttp://lattes.cnpq.br/2594285605805498Denise Mayumi TanakaEduardo Elias Vieira de CarvalhoDanielle Aparecida Gomes PereiraThayrine Rosa Damasceno2023-06-26T20:43:36Z2023-06-26T20:43:36Z2023-04-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/55370https://orcid.org/0000-0002-3442-9193porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2023-06-28T20:47:26Zoai:repositorio.ufmg.br:1843/55370Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2023-06-28T20:47:26Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
title Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
spellingShingle Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
Thayrine Rosa Damasceno
Cardiomiopatia chagásica
Miocardite
Capacidade funcional
Exercício aeróbico
Inflamação
Imagiologia de perfusão miocárdica
Doenças cardiovasculares
Chagas, Doença de
Reabilitação
Capacidade funcional
Exercícios físicos
title_short Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
title_full Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
title_fullStr Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
title_full_unstemmed Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
title_sort Avaliação dos efeitos do treinamento físico aeróbico nos parâmetros cardíacos e na capacidade funcional em modelo experimental de cardiomiopatia chagásica crônica
author Thayrine Rosa Damasceno
author_facet Thayrine Rosa Damasceno
author_role author
dc.contributor.none.fl_str_mv Luciano Fonseca Lemos de Oliveira
http://lattes.cnpq.br/2594285605805498
Denise Mayumi Tanaka
Eduardo Elias Vieira de Carvalho
Danielle Aparecida Gomes Pereira
dc.contributor.author.fl_str_mv Thayrine Rosa Damasceno
dc.subject.por.fl_str_mv Cardiomiopatia chagásica
Miocardite
Capacidade funcional
Exercício aeróbico
Inflamação
Imagiologia de perfusão miocárdica
Doenças cardiovasculares
Chagas, Doença de
Reabilitação
Capacidade funcional
Exercícios físicos
topic Cardiomiopatia chagásica
Miocardite
Capacidade funcional
Exercício aeróbico
Inflamação
Imagiologia de perfusão miocárdica
Doenças cardiovasculares
Chagas, Doença de
Reabilitação
Capacidade funcional
Exercícios físicos
description Chronic Chagas cardiomyopathy (CCC) is the most severe form of non-ischemic cardiomyopathy in Latin America. The persistent and low-intensity infection by Trypanosoma cruzi triggers a complex and long-lasting pathogenesis leading to the development of parasite-dependent myocardial damage, immune-mediated myocardial injury, microvascular disorders and cardiac dysautonomia, which contribute to the progression of ventricular dysfunction and reduction in cardiorespiratory fitness (CRF). Few studies suggest that aerobic physical training (APT) can lead to improvement in CRF and myocardial damage. The objectives of this study were to evaluate the effects of APT on myocardial morphology, function and perfusion and correlate these variables with inflammation and fibrosis in an experimental model of CCC using high-resolution in vivo images. Additionally, to investigate the influence of these alterations in the reduction of CRF. Furthermore, as a secondary objective, to analyze the cross-sectional areas of the skeletal muscle. In order to verify the clinical application of the study, we also performed a retrospective analysis of patients with CCC. Female Syrian hamsters with CCC and their controls (CT) were allocated into four groups: CCC-APT (n=22), CCC-SED (n=22), CT-APT (n=8) and CT-SED (n= 8). Seven months after infection, the animals were submitted to two-dimensional echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. The training was carried out for eight weeks, five times a week, for fifty minutes. After completing the APT protocol, the animals were reassessed, euthanized and cardiac tissue samples were collected for histopathological analysis. In the retrospective clinical analysis, four patients with CCC performed aerobic exercise at moderate to high intensity (60 to 85% of VO2peak) for twelve weeks. In the baseline evaluation, before allocation to the groups, chagasic animals showed similar peak oxygen consumption (VO2peak) (p>0.05), increased areas of myocardial perfusion defect (MPD) [4.5(2.7-8.5) vs 2.6(0.8-3.9), p=0.014] and reduction in left ventricular ejection fraction (LVEF) [46.9(40.3 -49 .7) vs 51.7 (49.4-53.3), p < 0.001] when compared to control animals. The correlation analysis showed that VO2peak correlated with MPD (r=-660; p<0.0001), LVEF (r=0.374; p=0.022), LVDD (r=-0.533; p=0.001) and LVSD (r=-0.49; p=0.001). Only MPD remained independently associated with VO2peak (adjusted r²=0.42). After animals allocation, mixed ANOVA showed reduced LVEF in chagasic groups [CCC-SED 46.72 (40.01-51.06)%] and CCC-APT [46.87 (42.35-50.10)%; p=0.015] when compared with CT-SED [53.06 (51.95-54.00)%, pANOVA=0.009]. After APT, mixed ANOVA identified reduced LVEF, significant increase in MPD over time, and more inflammation [(1.60±0.63); pANOVA<0.0001] and type 1 collagen [1.84 (1.22-2.82); pANOVA=0.008] in the CCC-SED group, when compared to the other groups. On the other hand, APT in the CCC-APT group reduced inflammation [(0.93±0.20); pANOVA<0.0001], prevented the progression of MPD and myocardial fibrosis, attenuated left ventricular dysfunction and improved the CRF. In animals with CCC, APT reduced inflammation, prevented the progression of MPD and fibrosis, attenuated left ventricular remodeling, improved functional capacity and promoted musculoskeletal structural recovery, reducing muscle atrophy. Furthermore, in patients with CCC, APT decreased MPD, improved LVEF and CRF.
publishDate 2023
dc.date.none.fl_str_mv 2023-06-26T20:43:36Z
2023-06-26T20:43:36Z
2023-04-25
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/55370
https://orcid.org/0000-0002-3442-9193
url http://hdl.handle.net/1843/55370
https://orcid.org/0000-0002-3442-9193
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
EEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONAL
Programa de Pós-Graduação em Ciências da Reabilitação
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
EEFFTO - ESCOLA DE EDUCAÇÃO FISICA, FISIOTERAPIA E TERAPIA OCUPACIONAL
Programa de Pós-Graduação em Ciências da Reabilitação
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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