Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 749
Filtrar
1.
Life Sci ; 230: 141-149, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129142

RESUMO

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.


Assuntos
Doença de Chagas/tratamento farmacológico , Doença de Chagas/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Antioxidantes/farmacologia , Cardiotônicos/metabolismo , Catalase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Citocinas/metabolismo , Modelos Animais de Doenças , Coração/fisiologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Masculino , Miocardite/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/metabolismo , Nitroimidazóis/farmacologia , Parasitemia/parasitologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismo
2.
Microbes Infect ; 21(1): 63-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30071300

RESUMO

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection - the indeterminate and chronic stages - has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Animais , Cardiomiopatia Chagásica/etiologia , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/patologia , Colesterol/metabolismo , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Mitocôndrias Cardíacas/fisiologia , Estresse Oxidativo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Trypanosoma cruzi/fisiologia
3.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
4.
J Electrocardiol ; 51(6): 1039-1043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497727

RESUMO

Chagas cardiomyopathy is the most harmful complication of Chagas disease. The electrocardiogram is a well-studied exam and has been considered an important tool for detection and evaluation of Chagas cardiomyopathy since the first years of its description. Many of its abnormalities have been described as associated with a worse prognosis. Serum BNP levels were described as inversely related to the left ventricular ejection fraction and as an independent predictor of death. It was not reported how electrocardiographic alterations correlate to NT-proBNP and its analog. The present study aims to describe the baseline electrocardiograms of a large cohort of patients with Chagas disease from endemic area and to establish an association between the number of electrocardiogram alterations and high levels of NT-ProBNP in Chagas disease patients. This study selected 1959 Chagas disease patients in 21 municipalities within a limited region in the northern part of the State of Minas Gerais (Brazil), 1084 of them had Chagas cardiomyopathy. NT-proBNP levels were suggestive of heart failure in 11.7% of this population. One or more electrocardiographic alterations have an Odds Ratio of 9.12 (CI 95% 5.62-14.80) to have NT-proBNP elevation. Considering the association between the number of 1, 2, and 3 or more alterations in electrocardiogram and NT-proBNP elevation, the ORs were 7.11 (CI 95% 4.33-11.67); 16.04 (CI 95% 9.27-27.77) and 47.82 (CI 95% 17.98-127.20), respectively. The presence and the number of typical electrocardiographic alterations of Chagas disease are independently associated with the severity of the cardiomyopathy.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Eletrocardiografia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Brasil , Cardiomiopatia Chagásica/sangue , Doença de Chagas/epidemiologia , Estudos de Coortes , Estudos Transversais , Doenças Endêmicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
5.
Rev Soc Bras Med Trop ; 51(6): 827-830, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517538

RESUMO

INTRODUCTION: We investigated the occurrence of coronary sinus abnormalities in the indeterminate form of Chagas disease (CD). METHODS: Differences between the maximum and minimum diameters of the coronary sinus (∆%) on echocardiography were evaluated in individuals with the indeterminate form of CD (n=14) and those without (n=16) CD. The association of the difference with abnormalities detected by echocardiography and myocardial scintigraphy was assessed. RESULTS: The mean Δ% values did not differ significantly between the groups. There was no correlation of the measurements with echocardiographic and myocardial scintigraphy findings. CONCLUSIONS: The coronary sinus evaluation revealed no differences between the groups.


Assuntos
Cardiomiopatia Chagásica/diagnóstico por imagem , Seio Coronário/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Cardiomiopatia Chagásica/fisiopatologia , Seio Coronário/parasitologia , Seio Coronário/fisiopatologia , Ecocardiografia , Feminino , Humanos , Masculino , Disfunção Ventricular Esquerda/fisiopatologia
6.
Neuroimmunomodulation ; 25(3): 119-128, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253402

RESUMO

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T. cruzi-seropositive (asymptomatic or with CCC) and sero-negative individuals were studied. Serum tumour necrosis factor (TNF)-α, interleukin (IL)-6, adipocytokines and the expression of their receptors in peripheral blood mononuclear cell (PBMC) were evaluated, together with other factors influencing the immune response. CCC patients showed major metabolic and hormonal abnormalities, in parallel with increased IL-6 and leptin serum levels. TNF-α receptor s, leptin and adiponectin receptors (ObR and Adipo-Rs respectively), as well as PPAR-γ expression in PBMCs from CCC patients were compatible with a counteracting response leading to an unfavourable immune-metabolic profile. These results suggest that persistently increased levels of immune-metabolic pro-inflammatory mediators along with the adverse endocrine anti-inflammatory response of CCC individuals, may contribute to the underlying mechanisms dealing with myocardial tissue damage.


Assuntos
Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/metabolismo , Imunidade Celular/fisiologia , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Índice de Gravidade de Doença , Adulto , Biomarcadores/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Citocinas/imunologia , Citocinas/metabolismo , Eletrocardiografia/tendências , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade
7.
Trials ; 19(1): 507, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30231899

RESUMO

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.


Assuntos
Cardiomiopatia Chagásica/tratamento farmacológico , Suplementos Nutricionais , Selenito de Sódio/uso terapêutico , Adolescente , Adulto , Idoso , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Suplementos Nutricionais/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Selenito de Sódio/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
8.
Arq Bras Cardiol ; 111(2): 182-190, 2018 Aug.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30088556

RESUMO

BACKGROUND: Heart failure (HF) is a severe public health problem because of its high morbidity and mortality and elevated costs, thus requiring better understanding of its course. In its complex and multifactorial pathogenesis, sympathetic hyperactivity plays a relevant role. Considering that sympathetic dysfunction is already present in the initial phases of chronic Chagas cardiomyopathy (CCC) and frequently associated with a worse prognosis, we assumed it could be more severe in CCC than in cardiomyopathies of other etiologies (non-CCC). OBJECTIVES: To assess the cardiac sympathetic dysfunction 123I-MIBG) of HF, comparing individuals with CCC to those with non-CCC, using heart transplant (HT) patients as denervated heart parameters. METHODS: We assessed 76 patients with functional class II-VI HF, being 25 CCC (17 men), 25 non-CCC (14 men) and 26 HT (20 men), by use of cardiac 123I-metaiodobenzylguanidine 123I-MIBG) scintigraphy, estimating the early and late heart-to-mediastinum ratio (HMR) of 123I-MIBG uptake and cardiac washout (WO%). The 5% significance level was adopted in the statistical analysis. RESULTS: The early and late HMR values were 1.73 ± 0.24 and 1.58 ± 0.27, respectively, in CCC, and 1.62 ± 0.21 and 1.44 ± 0.16 in non-CCC (p = NS), being, however, higher in HT patients (p < 0.001). The WO% values were 41.65 ± 21.4 (CCC), 47.37 ± 14.19% (non-CCC) and 43.29 ± 23.02 (HT), p = 0.057. The late HMR values showed a positive weak correlation with left ventricular ejection fraction (LVEF) in CCC and non-CCC (r = 0.42 and p = 0.045; and r = 0.49 and p = 0.015, respectively). CONCLUSION: Sympathetic hyperactivity 123I-MIBG) was evidenced in patients with class II-IV HF, LVEF < 45%, independently of the HF etiology, as compared to HT patients.


Assuntos
3-Iodobenzilguanidina/administração & dosagem , Cardiomiopatia Chagásica/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Transplante de Coração , Disautonomias Primárias/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Adulto , Cardiomiopatia Chagásica/fisiopatologia , Estudos Transversais , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Disautonomias Primárias/etiologia , Disautonomias Primárias/fisiopatologia , Cintilografia
9.
Arq Bras Cardiol ; 111(3): 364-372, 2018 Sep.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30088557

RESUMO

BACKGROUND: Chagas Disease (CD) is an important cause of morbimortality due to heart failure and malignant arrhythmias worldwide, especially in Latin America. OBJECTIVE: To investigate the association of obstructive sleep apnea (OSA) with heart remodeling and cardiac arrhythmias in patients CD. METHODS: Consecutive patients with CD, aged between 30 to 65 years old were enrolled. Participants underwent clinical evaluation, sleep study, 24-hour Holter monitoring, echocardiogram and ambulatory blood pressure monitoring. RESULTS: We evaluated 135 patients [age: 56 (45-62) years; 30% men; BMI: 26 ± 4 kg/m2, Chagas cardiomyopathy: 70%]. Moderate to severe OSA (apnea-hypopnea index, AHI, ≥ 15 events/h) was present in 21% of the patients. OSA was not associated with arrhythmias in this population. As compared to patients with mild or no OSA, patients with moderate to severe OSA had higher frequency of hypertension (79% vs. 72% vs. 44%, p < 0.01) higher nocturnal systolic blood pressure: 119 ± 17 vs. 113 ± 13 vs. 110 ± 11 mmHg, p = 0.01; larger left atrial diameter [37 (33-42) vs. 35 (33-39) vs. 33 (30-36) mm, p < 0.01]; and a greater proportion of left ventricular dysfunction [LVEF < 50% (39% vs. 28% vs. 11%), p < 0.01], respectively. Predictor of left atrial dimension was Log10 (AHI) (b = 3.86, 95% CI: 1.91 to 5.81; p < 0.01). Predictors of ventricular dysfunction were AHI > 15 events/h (OR = 3.61, 95% CI: 1.31 - 9.98; p = 0.01), systolic blood pressure (OR = 1.06, 95% CI: 1.02 - 1.10; p < 0.01) and male gender (OR = 3.24, 95% CI: 1.31 - 8.01; p = 0.01). CONCLUSIONS: OSA is independently associated with atrial and ventricular remodeling in patients with CD.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatia Chagásica/complicações , Apneia Obstrutiva do Sono/etiologia , Remodelação Ventricular , Adulto , Idoso , Análise de Variância , Antropometria , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Estatísticas não Paramétricas , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
10.
Mem Inst Oswaldo Cruz ; 113(10): e180224, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30133549

RESUMO

BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) levels have been shown to be lower in patients with Chagas cardiomyopathy (ChC) than in patients with non-dilated chagasic cardiomyopathy. However, its prognostic value was not established in patients with ChC. METHODS: Forty-nine patients with ChC (50 ± 7 years, New York Heart Association "NYHA" I-III); were evaluated by echocardiography, exercise testing, and blood analysis. Serum BDNF levels were determined using enzyme-linked immunosorbent assay sandwich. Patients were followed-up, and cardiac death was considered the end-point. The survival analyses were performed using Kaplan-Meier and Cox regression. RESULTS: After 39 ± 14 months of follow-up, 12 patients (25%) died. The concentration of 2.5 ng/mL was the optimal cut-off value to predict survival with significant difference between the groups with low (≤ 2.5 ng/mL) and high (> 2.5 ng/mL) BDNF levels (p = 0.006). Lower serum BDNF levels (hazards ratio (HR) 1.1, 95% confidence interval (CI) 1.1-1.4; p = 0.001), peak oxygen uptake (HR 1.2, 95% CI 1.0-1.3; p = 0.009), and left ventricular ejection fraction (HR 0.8, 95% CI 0.7-0.9; p = 0.001) were the independent predictors of survival. The combination of low serum BDNF levels and reduced left ventricular ejection fraction were highly predictive of death (HR 5.6, 95% CI: 1.2-9.7; p = 0.026). CONCLUSION: In patients with ChC, reduced serum BDNF levels, especially if associated with systolic function, may provide useful prognostic information.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Cardiomiopatia Chagásica/sangue , Adulto , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia , Ensaio de Imunoadsorção Enzimática , Teste de Esforço , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Prognóstico , Estudos Prospectivos , Padrões de Referência , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Fatores de Tempo
11.
PLoS Pathog ; 14(5): e1007065, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29851986

RESUMO

Chagasic cardiomyopathy is caused by Trypanosoma cruzi infection. Poly(ADP-ribose) polymerase 1 (PARP1) is known for its function in nuclear DNA repair. In this study, we have employed genetic deletion and chemical inhibition approaches to determine the role of PARP1 in maintaining mtDNA dependent mitochondrial function in Chagas disease. Our data show that expression of PARP1 and protein PARylation were increased by >2-fold and >16-fold, respectively, in the cytosolic, nuclear, and mitochondrial fractions of the human cardiac myocytes and the myocardium of wildtype (WT) mice chronically infected with T. cruzi. The nuclear and cytosolic PARP1/PAR did not interfere with the transcription and translation of the components of the mtDNA replisome machinery in infected cardiomyocytes and chagasic murine myocardium. However, PARP1 binding to Polymerase γ and mtDNA in mitochondria were increased, and associated with a loss in mtDNA content, mtDNA-encoded gene expression, and oxidative phosphorylation (OXPHOS) capacity, and an increase in mitochondrial ROS production in cells and heart of WT mice infected with T. cruzi. Subsequently, an increase in oxidative stress, and cardiac collagen deposition, and a decline in LV function was noted in chagasic mice. Genetic deletion of PARP1 or treatment with selective inhibitor of PARP1 (PJ34) improved the mtDNA content, mitochondrial function, and oxidant/antioxidant balance in human cardiomyocytes and chronically infected mice. Further, PARP1 inhibition was beneficial in preserving the cardiac structure and left ventricular function in chagasic mice. We conclude that PARP1 overexpression is associated with a decline in Pol γ-dependent maintenance of mtDNA content, mtDNA-encoded gene expression, and mitochondrial respiratory function, and subsequently contributes to an increase in mtROS and oxidative stress in chagasic myocardium. Inhibition of mitochondrial PARP1/PAR offers a novel therapy in preserving the mitochondrial and LV function in chronic Chagas disease.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Polimerase do DNA Mitocondrial/genética , DNA Mitocondrial/fisiologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Animais , Antioxidantes/metabolismo , Células Cultivadas , Cardiomiopatia Chagásica/genética , Imunoprecipitação da Cromatina , DNA de Protozoário/fisiologia , Células HeLa , Coração/fisiologia , Humanos , Imunoprecipitação , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/fisiologia , Células Musculares/metabolismo , Miócitos Cardíacos/citologia , Estresse Oxidativo , Fenantrenos/farmacologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/genética , Espécies Reativas de Oxigênio/metabolismo , Trypanosoma cruzi/genética , Função Ventricular Esquerda/fisiologia
12.
Basic Res Cardiol ; 113(4): 29, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29905892

RESUMO

In the cardiomyocyte, CaMKII has been identified as a nodal influencer of excitation-contraction and also excitation-transcription coupling. Its activity can be regulated in response to changes in intracellular calcium content as well as after several post-translational modifications. Some of the effects mediated by CaMKII may be considered adaptive, while effects of sustained CaMKII activity may turn into the opposite and are detrimental to cardiac integrity and function. As such, CaMKII has long been noted as a promising target for pharmacological inhibition, but the ubiquitous nature of CaMKII has made it difficult to target CaMKII specifically where it is detrimental. In this review, we provide a brief overview of the physiological and pathophysiological properties of CaMKII signaling, but we focus on the physiological and adaptive functions of CaMKII. Furthermore, special consideration is given to the emerging role of CaMKII as a mediator of inflammatory processes in the heart.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomiopatia Chagásica/enzimologia , Mediadores da Inflamação/metabolismo , Miocardite/enzimologia , Miocárdio/enzimologia , Animais , Apoptose , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/química , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/fisiopatologia , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Humanos , Miocardite/genética , Miocardite/patologia , Miocardite/fisiopatologia , Miocárdio/patologia , Necrose , Conformação Proteica , Transdução de Sinais , Relação Estrutura-Atividade
13.
PLoS Negl Trop Dis ; 12(6): e0006567, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29897909

RESUMO

BACKGROUND: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. METHODS: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. RESULTS: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. CONCLUSIONS: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Adulto , Arritmias Cardíacas/parasitologia , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/complicações , Doença de Chagas/parasitologia , Criança , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Razão de Chances , Prevalência
14.
J Nucl Med ; 59(9): 1430-1436, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29700129

RESUMO

Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n = 34) were infected with 3.5 × 104 to 105 trypomastigote forms of Trypanosoma cruzi, Y strain, and 6-10 mo afterward underwent in vivo imaging including resting 99mTc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and 18F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. Results: MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced 18F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction (P = 0.012), a higher wall motion score index (P = 0.004), and a higher extent of inflammatory infiltration (P = 0.018) but a similar extent of fibrosis (P = 0.15) and similar microvascular diameter and density (P > 0.05). Segments with an MPD (n = 65), as compared with normally perfused regions in the same animal (n = 156), showed a higher wall motion score index (P = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Conclusion: Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium.


Assuntos
Cardiomiopatia Chagásica/fisiopatologia , Circulação Coronária , Animais , Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/patologia , Doença Crônica , Cricetinae , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18 , Microvasos/diagnóstico por imagem , Microvasos/fisiopatologia , Imagem de Perfusão do Miocárdio , Miocárdio/patologia , Tomografia por Emissão de Pósitrons , Sístole/fisiologia , Sobrevivência de Tecidos , Disfunção Ventricular Esquerda/fisiopatologia
15.
Europace ; 20(11): 1813-1818, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29509903

RESUMO

Aims: Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results: This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. Conclusion: This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.


Assuntos
Terapia de Ressincronização Cardíaca , Cardiomiopatia Chagásica , Brasil/epidemiologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/terapia , Desfibriladores Implantáveis , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico
16.
Parasit Vectors ; 11(1): 72, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382361

RESUMO

BACKGROUND: Cardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation. METHODS: Cardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells. After two passages, cells were infected with T. cruzi (Y strain) and analyzed at different times for determination of infectivity, activation and production of extracellular matrix components (fibronectin, laminin and collagen IV) by immunofluorescence and western blot. RESULTS: At second passage, cultures were enriched in CFs (95% of fibroblasts and 5% of cardiomyocytes), as revealed by presence of alpha-smooth muscle actin (α-SMA) and discoidin domain receptor 2 (DDR2) and absence of sarcomeric tropomyosin (ST) protein expression. Trypanosoma cruzi infection induced fibroblast-myofibroblast transition, with increased expression of α-SMA after 6 and 24 h post-infection (hpi). Fibronectin was increased at 6, 24 and 48 hpi, laminin was increased at 6 and 24 hpi and collagen IV was increased at 6 hpi. CONCLUSIONS: Our results showed that T. cruzi activates CFs, inducing activation and exacerbates ECM production. Furthermore, our data raise the possibility of the involvement of CFs in heart fibrosis during Chagas disease.


Assuntos
Proteínas da Matriz Extracelular/genética , Fibroblastos/parasitologia , Miofibroblastos/parasitologia , Trypanosoma cruzi/fisiologia , Animais , Western Blotting , Células Cultivadas , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Colágeno/genética , Fibroblastos/fisiologia , Fibronectinas/genética , Imunofluorescência , Laminina/genética , Camundongos , Miofibroblastos/fisiologia
17.
Pacing Clin Electrophysiol ; 41(3): 238-245, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29315657

RESUMO

BACKGROUND: It has been difficult to prove that "catecholamine-induced cardiomyopathy" contributes to the mechanism of sudden cardiac death in Chagas heart disease. Also, it is almost impossible to rule out the possibility that it is not involved in the process. More importantly, the vagal-cholinergic pathway in the ventricle plays a direct role in the prevention of the initiation of complex ventricular arrhythmias, including nonsustained ventricular tachycardia, ventricular fibrillation responsible for sudden death. OBJECTIVE: To determine frequency of parasympathetic autonomic indices among the different groups of risk of cardiovascular death when stratified by Rassi score. METHODS: Patients with Chagas heart disease were selected and divided into three risk groups by Rassi score. A fourth group, non-Chagas group, was of similar age and gender. All were subjected to analysis of heart rate variability during controlled breathing (RSA) and tilt table passive test (tilt test). High frequency and low frequency/high frequency ratio were calculated and presented by box-plot. Also, t-test was used to compare the two groups. RESULTS: It was observed that the parasympathetic and sympathetic component were affected, when the risk group increased the response was worsened to the stimulus (RSA or Tilt). Also, the low-risk group was jeopardized, when compared to the non-Chagas group. CONCLUSION: The loss of parasympathetic modulation was present in all Rassi risk groups, including the low risk, indicating that a morphological change of the myocardium represents a detectable neurofunctional change.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cardiomiopatia Chagásica/mortalidade , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Teste da Mesa Inclinada
18.
Am J Cardiol ; 121(3): 364-369, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29191568

RESUMO

We sought to investigate the prognostic value of the electrocardiogram (ECG) electrical axes (P wave, T wave and QRS) as predictors of mortality in the 14-year follow-up of the prospective cohort of all residents ≥60 years living in the southeastern Brazilian city of Bambuí, a population with high prevalence of Chagas disease (ChD). Baseline ECG axes were automatically measured with normal values defined as follows: P-wave axis 0° to 75°, QRS axis -30° to 90°, and T axis 15° to 75°. Participants underwent annual follow-up visits and death was verified using death certificates. Cox proportional hazards regression was used to assess the prognostic value of ECG axes for all-cause mortality, after adjustment for potential confounders. From 1,742 qualifying residents, 1,462 were enrolled, of whom 557 (38.1%) had ChD. Mortality rate was 51.9%. In multivariable adjusted models, abnormal P-wave axis was associated with a 48% (hazard ratio [HR] = 1.48 [95% confidence interval (CI) 1.16-1.88]) increased mortality risk in patients with ChD and 43% (HR = 1.43 [CI 1.13-1.81]) in patients without ChD. Abnormal QRS axis was associated with a 34% (HR = 1.34 [CI 1.04-1.73]) increased mortality risk in patients with ChD, but not in individuals without ChD. Similarly, in the ChD group, abnormal T-wave axis was associated with a 35% (HR = 1.35 [CI 1.07-1.71]) increased mortality, but not in patients without ChD. In conclusion, abnormal P-wave, QRS, and T-wave axes were associated with increased all-cause mortality in patients with ChD. Abnormal P-wave axis was associated with mortality also among those without ChD, being the strongest predictor among ECG variables.


Assuntos
Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Idoso , Brasil , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Fatores de Risco
19.
Microbes Infect ; 20(1): 25-36, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28951318

RESUMO

Infection with Trypanosoma cruzi causes Chagas disease and results in myocardial inflammation and cardiomyopathy. Downregulated Hexim1 expression, as in Hexim1+/- mice, reduces cardiac inflammation and fibrosis following ischemic stress. We asked whether reduced expression of Hexim1 would also afford protection against T. cruzi-induced cardiomyopathy. C57BL/6J (wild type - WT) and Hexim1+/- mice were infected with sub-lethal doses of T. cruzi (Brazil strain), and cardiac function, serologic markers of inflammation and tissue pathology were examined. Infected Hexim1+/- mice had compromised cardiac function, altered expression of both pro- and anti-inflammatory cytokines, and increased inflammation and fibrosis. Cardiac failure was evidenced by severely diminished heart rate, compensatory increase in respiratory rate, and abnormally high left ventricular mass with severe transmural inflammation. Lungs displayed intense peribronchial inflammation and fibrosis extending into the parenchyma. We also observed Smad3-serine208 phosphorylation in hearts and lungs of infected mice, suggesting increased TGF-ß signaling pathway activity. This was more pronounced in Hexim1+/- mice and correlated with increased fibrosis in these tissues. Conspicuous splenomegaly in the Hexim1+/- mice most likely resulted from the observed extensive white pulp expansion. T. cruzi infection induced colonic dilatation and marked villous atrophy in both the WT and Hexim1+/- mice but more so in the latter. The profound exacerbation of pathologic findings suggests a protective role for Hexim1 in T. cruzi infection.


Assuntos
Cardiomiopatia Chagásica/patologia , Fatores de Transcrição/genética , Trypanosoma cruzi/patogenicidade , Animais , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Citocinas/biossíntese , Modelos Animais de Doenças , Coração/fisiopatologia , Inflamação/metabolismo , Intestinos/imunologia , Intestinos/patologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/imunologia , Miocárdio/patologia , Fosforilação , Proteína Smad3/metabolismo , Baço/patologia
20.
Rev Port Cardiol ; 36(12): 927-934, 2017 Dec.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29223851

RESUMO

BACKGROUND: Anaerobic threshold (AT) is recognized as objective and direct measurement that reflects variations in metabolism of skeletal muscles during exercise. Its prognostic value in heart diseases of non-chagasic etiology is well established. However, the assessment of risk of death in Chagas heart disease is relatively well established by Rassi score. But, the added value that AT can bring to Rassi score has not been studied yet. OBJECTIVES: To assess whether AT presents additional effect to Rassi score in patients with chronic Chagas' heart disease. METHODS: Prospective research of dynamic cohort by review of 150 medical records of patients. Were selected for cohort 45 medical records of patients who underwent cardiopulmonary exercise testing between 1996-1997 and followed until September 2015. Data analysis to detect association between studied variables can be seen using a logistic regression model. The suitability of the models was verified using ROC curves and the coefficient of determination R2. RESULTS: 8 patients (17.78%) died by September 2015, with 7 of them (87.5%) from cardiovascular causes, of which 4 (57.14%) were considered on high risk by Rassi score. With Rassi score as independent variable, and death being the outcome, we obtained an area under the curve (AUC)=0.711, with R2=0.214. Instituting AT as independent variable, we found AUC=0.706, with R2=0.078. When we define Rassi score and AT as independent variables, it was obtained AUC=0.800 and R2=0.263. CONCLUSION: when AT is included in logistic regression, it increases by 5% the explanation (R2) to the death estimation.


Assuntos
Limiar Anaeróbio , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Modelos Estatísticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Saúde da População Urbana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA