RESUMO
Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-ß) although other cytokines may be involved in the chagasic cardiomyopathy.
Assuntos
Cardiomiopatia Chagásica/metabolismo , Sistema de Condução Cardíaco/metabolismo , Mediadores da Inflamação/metabolismo , Miocardite/metabolismo , Miócitos Cardíacos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo , Potenciais de Ação , Animais , Anti-Inflamatórios/uso terapêutico , Remodelamento Atrial , Cardiomiopatia Chagásica/tratamento farmacológico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/parasitologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Contração Miocárdica , Miocardite/tratamento farmacológico , Miocardite/parasitologia , Miocardite/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/parasitologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Remodelação VentricularRESUMO
Transforming growth factor-ß (TGF-ß) influences the development of myocardiopathy in Chagas disease through regulation of (i) parasite invasion of heart cells, (ii) an intracellular parasite cycle, (iii) inflammation and immune response, (iv) heart fibrosis and remodeling, and (v) gap junction modulation and heart conduction. In this review, we discuss the rationale for developing TGF-ß signaling-interfering therapies as adjuvant approaches for the management of the cardiac alterations of Chagas disease-affected patients.
Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Doença de Chagas/tratamento farmacológico , Fator de Crescimento Transformador beta/metabolismo , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Doença de Chagas/parasitologia , Doença de Chagas/fisiopatologia , Desenho de Fármacos , Junções Comunicantes/parasitologia , Sistema de Condução Cardíaco/parasitologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/parasitologia , Transdução de Sinais/efeitos dos fármacos , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Trifascicular block, which consists of impaired conduction in the three main fascicles of the ventricular conduction system, may progress to high-grade or complete atrioventricular block. Exceptionally, it is possible to register in the same patient paroxysmal alternating atrioventricular block and bilateral bundle branch block. This is the electrocardiogram of a male, 60 year-old patient coming from an endemic area, with positive serology for Chagas disease, with the exclusively dromotropic form (there are no signs of cardiac muscle involvement), manifest by repetitive pre-syncope and syncope episodes.
Assuntos
Bloqueio Atrioventricular/parasitologia , Bloqueio de Ramo/parasitologia , Doença de Chagas/complicações , Sistema de Condução Cardíaco/parasitologia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio de Ramo/fisiopatologia , Doença de Chagas/parasitologia , Doença de Chagas/fisiopatologia , Eletrocardiografia Ambulatorial , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Síncope/parasitologiaRESUMO
The aim of this study was to obtain an experimental animal model of destruction of cardiac neurons in order to investigate the behavior of the cardiac nervous system of hamsters chronically infected with Trypanosoma cruzi. We counted the neuronal cells of the cardiac autonomic nervous plexus in hamsters inoculated with 35,000 blood forms of three different T. cruzi strains and killed 5, 8 and 10 months after infection. We showed for the first time severe neuronal destruction in an experimental animal model with characteristics similar to those observed in human Chagas'disease.
Assuntos
Doença de Chagas/patologia , Sistema de Condução Cardíaco/parasitologia , Neurônios/parasitologia , Animais , Doença de Chagas/parasitologia , Cricetinae , Feminino , Sistema de Condução Cardíaco/patologia , Humanos , Masculino , Mesocricetus , Neurônios/patologia , Trypanosoma cruziRESUMO
The histopathology of the heart is described in an acute case of Chagas' disease (DC). Lesions involving the conducting system (SC) and the autonomic intracardiac nervous system (SNAIC) are emphasized. Light microscopy showed acute pan-carditis with plenty of Trypanosoma cruzi amastigotes within heart muscle cells. Multiple inflammatory foci were found in the SC with parasitic nests within the atrioventricular node and left his bundle. There were also severe atrial periganglionitis and perineuritis with or without peripheral involvement of those structures. Apparently there was no cardiac neuronal depopulation. The epidemiological study suggested transmission through Rhodnius pictipes. To the best of our knowledge, this is the first reported case of acute DC from the Amazonian basin with systematized microscopy study of the SC and SNAIC.
Assuntos
Humanos , Animais , Masculino , Pré-Escolar , Coração/irrigação sanguínea , Sistema de Condução Cardíaco/patologia , Cardiomiopatia Chagásica/patologia , Sistema Nervoso Autônomo/patologia , Doença Aguda , Brasil , Coração/parasitologia , Evolução Fatal , Sistema de Condução Cardíaco/parasitologia , Cardiomiopatia Chagásica/parasitologia , Miocárdio/patologia , Sistema Nervoso Autônomo/parasitologia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
The histopathology of the heart is described in an acute case of Chagas' disease (DC). Lesions involving the conducting system (SC) and the autonomic intracardiac nervous system (SNAIC) are emphasized. Light microscopy showed acute pan-carditis with plenty of Trypanosoma cruzi amastigotes within heart muscle cells. Multiple inflammatory foci were found in the SC with parasitic nests within the atrioventricular node and left his bundle. There were also severe atrial periganglionitis and perineuritis with or without peripheral involvement of those structures. Apparently there was no cardiac neuronal depopulation. The epidemiological study suggested transmission through Rhodnius pictipes. To the best of our knowledge, this is the first reported case of acute DC from the Amazonian basin with systematized microscopy study of the SC and SNAIC.
Assuntos
Sistema Nervoso Autônomo/patologia , Cardiomiopatia Chagásica/patologia , Sistema de Condução Cardíaco/patologia , Coração/inervação , Doença Aguda , Animais , Sistema Nervoso Autônomo/parasitologia , Brasil , Cardiomiopatia Chagásica/parasitologia , Pré-Escolar , Evolução Fatal , Coração/parasitologia , Sistema de Condução Cardíaco/parasitologia , Humanos , Masculino , Miocárdio/patologia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Although mice infected with Trypanosoma cruzi develop a wide variety of electrocardiographic (ECG) alterations, the typical isolated right bundle branch block or its association with the left anterior hemiblock patterns are not found in this model. This has been explained as related to topographic differences in the anatomy of the murine conducting system. However, there is no conclusive evidence that the murine conducting system differs from the human system. In this study, the anatomy of the murine conducting system is described, as well as its involvement in the chronic stages of experimental infection. 24 three-month-old C3H mice were infected with 50 bloodstream forms of T. cruzi, Tulahuén strain. Animals were killed after 3, 8 and 12 months. Whole frontal sections of the heart, including the conducting system, were serially studied. The sinoatrial node was located in the right atrial appendage, or in the junction between the superior vena cava and the right atrium, or "riding" on the interatrial septum. The atrioventricular (A-V) node and the His bundle showed a similar anatomic course to that in man. Therefore, there was no important anatomical difference that might have explained the lack of the ECG patterns observed in human chagasic myocardiopathy. The inflammatory involvement and the lesions of the conducting system were diverse and rarely severe. No significant difference was observed in animals killed at different times. The lesions in the working myocardium were similar to those observed in humans (chronic inflammatory infiltrates). Nevertheless, the topography of lesions was different: there was a selective involvement in the neighbourhood of the A-V groove.(ABSTRACT TRUNCATED AT 250 WORDS)