RESUMO
BACKGROUND: Chronic chagasic cardiomyopathy is an inflammatory disease that occurs in approximately 30% of patients infected by the protozoan Trypanosoma cruzi, and it has a profile of high morbidity and mortality. The worst prognosis and the progression of this cardiomyopathy are associated with an exacerbated immune response and the production of proinflammatory cytokines, which also occur in other cardiomyopathies. Some nutrients, including omega-3 polyunsaturated fatty acids (PUFAs), promote the inhibition and/or stimulation of cytokine production. The objective of this trial is to study the effects of omega-3 PUFA supplementation on the inflammatory response and lipid profile in patients with chronic chagasic cardiomyopathy. METHODS/DESIGN: This is a parallel, randomized, placebo-controlled, double-blind clinical trial with 40 patients that will be conducted at a reference unit for Chagas disease patients, where the patients will be selected. The study will include patients with chronic chagasic cardiomyopathy who are 18 years of age or older. The exclusion criteria are (a) ongoing diarrheal disease, (b) inflammatory bowel disease, (c) diabetes or other endocrine disease, (d) use of fibrates, niacin, or statins, (e) use of anti-inflammatory drugs, (f) pregnant and lactating women, (g) use of vitamin, mineral, or omega-3 supplementation during the previous 30 days, (h) hospital admission during the study, and (i) other associated cardiomyopathies. The intervention will be treatment with omega-3 PUFAs at a dose of 3 g/day for 8 weeks, compared to placebo (corn oil). The primary endpoints will be the concentrations of inflammatory markers (interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and transforming growth factor (TGF)ß). Secondary endpoints will be the fasting glucose, lipid, and anthropometric profiles. For statistical analysis, we plan to run either a t test or Wilcoxon test (numerical variables) and Pearson's χ2 or Fisher's exact test (categorical data), as appropriate. DISCUSSION: Evidence suggests that the anti-inflammatory action of omega-3 PUFAs may have beneficial effects on chronic chagasic cardiomyopathy, as shown for other cardiomyopathies, due to improved control of the inflammatory response. At the end of the study, we predict that patients will have lower inflammatory markers and an improved metabolic and anthropometric profile. TRIAL REGISTRATION: Current Controlled Trials NCT01863576.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Projetos de Pesquisa , Biomarcadores/sangue , Brasil , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Distribuição de Qui-Quadrado , Doença Crônica , Protocolos Clínicos , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Masculino , Avaliação Nutricional , Estado Nutricional , Fatores de Tempo , Resultado do TratamentoRESUMO
Chagas' disease caused by infection with Trypanosoma cruzi leads to a myocardiopathy that evolves from the acute to the chronic phase. Magnetic resonance imaging (MRI) is an important tool for monitoring cardiac morphology and function both in humans and in animals. In the present work, we present a brief review of MRI applications for the study of ventricular hypertrophy and dilatation of the right ventricle in murine models of Chagas' disease. Studies using MRI demonstrate an increase in right ventricular chamber dimension during both phases of infection, indicating that increase of the right ventricle is a marker for experimental chagasic myocardiopathy. Based on previous studies using MRI in these models we propose that this technique is an excellent approach for monitoring heart functionality from the acute through the chronic phase of infection in different parasite-host pairs and for monitoring the efficacy of cardioprotective or immune-therapeutic agents.
Assuntos
Cardiomiopatia Chagásica/patologia , Ventrículos do Coração/patologia , Hipertrofia Ventricular Direita/diagnóstico , Imageamento por Ressonância Magnética/métodos , Infecções Protozoárias em Animais/diagnóstico , Disfunção Ventricular Direita/diagnóstico , Animais , Dilatação Patológica/diagnóstico , Dilatação Patológica/parasitologia , Modelos Animais de Doenças , Ventrículos do Coração/fisiopatologia , Interações Hospedeiro-Parasita , Hipertrofia Ventricular Direita/parasitologia , Infecções Protozoárias em Animais/parasitologia , Disfunção Ventricular Direita/parasitologiaRESUMO
Chagas' disease, caused by Trypanosoma cruzi, leads to acute myocarditis and chronic cardiomyopathy. Myocardial structure and function were evaluated in T. cruzi (Brazil strain)-infected CD1 mice by histopathology, cardiac gated magnetic resonance imaging (MRI) and transthoracic echocardiography. There was a significant reduction in inflammation and fibrosis in infected mice treated early in infection. In mice treated late in infection, echocardiography revealed a significant increase in the end diastolic diameter and a decrease in percent fractional shortening and relative wall thickness. MRI revealed an increase in the right ventricular internal dimension. These findings, consistent with a dilated cardiomyopathy, were ameliorated in the early but not in the late treatment group, demonstrating that late treatment with verapamil is ineffective in reversing the development of chagasic cardiomyopathy in chronically infected mice. Our data underscore the hypothesis that early events determine the progression to cardiomyopathy and that early treatment with verapamil can prevent such progression.
Assuntos
Cardiomiopatia Chagásica/prevenção & controle , Doença de Chagas/tratamento farmacológico , Verapamil/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacologia , Cardiomiopatia Dilatada/fisiopatologia , Doença de Chagas/patologia , Doença de Chagas/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Átrios do Coração/patologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Imageamento por Ressonância Magnética , Camundongos , Miocardite/patologia , Parasitemia , Verapamil/uso terapêuticoRESUMO
Chagasic patients with cardiomyopathy have low levels of selenium (Se), a fundamental trace element. We evaluated the effect of supplementing infected mice with Se (0.25-16 ppm). Supplementation with 0.25 or 1 ppm Se led to parasitaemia and survival curves similar to those of the control group. Mice treated with 4-16 ppm showed a dose-dependent decrease of parasitaemia, significant for the highest concentration. This was probably due to a direct effect on the parasites, which were lysed after in vitro incubation with Se. Survival rates did not change significantly; however, heart damage was reduced in infected mice supplemented with 4 ppm Se, as indicated by a lower cardiac isoform of creatine kinase levels. Our results imply that Se supplementation does not lead to a general protection during infection, but may help protect the heart from inflammatory damage. The effect of Se supplementation in the course of T. cruzi infection depends on the host-parasite pair employed.
Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Miocárdio/patologia , Selênio/uso terapêutico , Doença Aguda , Animais , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Camundongos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Parasitemia/patologia , Selênio/administração & dosagem , Resultado do Tratamento , Trypanosoma cruzi/patogenicidadeRESUMO
Selenium (Se) deficiency is linked with some cardiomyopathies. Its status was determined in 170 patients with chronic Chagas' disease from 2 Brazilian regions (Rio de Janeiro and Belo Horizonte), clinically stratified into groups as follows: indeterminate or asymptomatic (IND); cardiac asymptomatic (CARDa); cardiac symptomatic with moderate to severe heart dysfunction (CARDb); and healthy adults (HA), used for comparison. In most HA, Se levels were normal, excluding an overall Se deficiency. Se was significantly lower in CARDb than in HA, IND, or CARDa patients. This was not associated with a concomitant decrease in activity of glutathione peroxidase. Thyrotropin was normal, excluding iodine deficiency. Se correlated positive and significantly with ventricular ejection fraction (assessed via echocardiography). Asymptomatic children with acute Chagas' disease had normal Se as well as 5 noninfectious cases of cardiomyopathy. Low Se was found in 6 of 10 chagasic patients with digestive megasyndromes. Thus, the decrease in Se in chagasic patients seems to be a biological marker for Trypanosoma cruzi infection and related to the progression of pathology.
Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Glutationa Peroxidase/sangue , Selênio/deficiência , Animais , Anticorpos Antiprotozoários/sangue , Brasil , Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Criança , Progressão da Doença , Humanos , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Análise de Regressão , Selênio/sangue , Tireotropina/sangue , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Selenium is an essential trace element and its deficiency was implicated in heart diseases. We recently showed low Se levels in chronic chagasic patients with cardiomyopathy. Herein, mice were depleted in Se by feeding the mothers with chow containing only 0.005 mg Se/kg and maintaining this diet for offspring, that were further infected with Trypanosoma cruzi. Survival rate was significantly lower in Se deficient than in control mice. Parasitemia was similar in all groups. Necrotic heart lesions were found after infection (high CK-MB levels). No outbreaks of parasite growth were detected in chronic survivors submitted or not to a second Se depletion. The present results confirm our hypothesis that a nutritional deficiency in Se is associated to a higher mortality during T. cruzi infection. The potential beneficial effect of Se supplementation is a perspective. Hypothesis to explain the higher susceptibility of Se-depleted mice to T. cruzi infection are discussed.