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1.
Front Immunol ; 11: 1386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733459

RESUMO

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while the others remain asymptomatic (ASY). IFN-γ and IFN-γ-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-γ-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-γ production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-γ production and Th1 T cell differentiation in CCC development. Methods: We studied a Brazilian population including 315 CCC cases and 118 ASY subjects. We assessed 35 Tag SNPs designed to represent all the genetic information contained in the IL12B, IL10, IFNG, and IL4 genes. Results: We found 2 IL12 SNPs (rs2546893, rs919766) and a trend of association for a IL10 SNP (rs3024496) to be significantly associated with the ASY group. these associations were confirmed by multivariate analysis and allele tests. The rs919766C, 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development. Conclusions: Our data show that novel polymorphisms affecting IL12B and IL10, but not IFNG or IL4 genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-γ production associated with CCC is genetically controlled.

2.
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.
In. Soeiro, Alexandre de Matos; Leal, Tatiana de Carvalho Andreucci Torres; Oliveira Junior, Múcio Tavares de; Kalil Filho, Roberto. Manual da condutas da emergência do InCor: cardiopneumologia / IInCor Emergency Conduct Manual: Cardiopneumology. São Paulo, Manole, 2ª revisada e atualizada; 2017. p.529-536.
Monografia em Português | LILACS | ID: biblio-848486
5.
PLoS One ; 10(7): e0131447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26147101

RESUMO

BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.


Assuntos
Adipocinas/sangue , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Inflamação/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adiponectina/sangue , Adulto , Cardiomiopatia Chagásica/sangue , Eletrocardiografia , Feminino , Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Inflamação/sangue , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Disfunção Ventricular Esquerda/sangue
6.
Arq. bras. cardiol ; 105(1): 28-36, July 2015. tab
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: lil-755004

RESUMO

Background:

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

Objective:

To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.

Methods:

10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.

Results:

Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.

Conclusion:

An impairment of LA functions in Chagas cardiomyopathy was observed.

.

Fundamento:

A doença de Chagas é uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a função do átrio esquerdo (AE) nessa doença.

Objetivo:

Avaliar as diferenças nas funções do AE (reservatório, conduto e bomba) e sua correlação com os parâmetros ecocardiográficos das funções sistólica e diastólica do ventrículo esquerdo (VE).

Método:

10 controles (GC) e os seguintes pacientes com doença de Chagas: 26 com a forma indeterminada (GI); 30 com alterações eletrocardiográficas (GII); e 19 com disfunção de VE (GIII). Todos os pacientes foram submetidos a ecocardiografia bidimensional e em modo M, Doppler pulsado e Doppler tecidual.

Resultados:

Função de reservatório (fração de esvaziamento total: FET) (p < 0,0001), mais baixa no GIII do que no GC (p = 0,003), GI (p < 0,001) e GII (p < 0,001). Função de conduto (fração de esvaziamento passivo: FEP) (p = 0,004), mais baixa no GIII (GIII e GC, p = 0.06; GI e GII, p = 0.06; e GII e GIII, p = 0,07). Função de bomba (fração de esvaziamento ativo: FEA) (p = 0,0001), mais baixa no GIII do que no CG (p = 0,05), GI (p<0,0001) e GII (p = 0,002). Observou-se uma correlação negativa entre E/e’média e as funções de reservatório e de bomba (FET e FEA), e uma correlação positiva entre as ondas e’média e s’ (paredes septal e lateral) e as funções de reservatório, conduto e bomba.

Conclusão:

Observou-se comprometimento das funções do AE na miocardiopatia chagásica.

.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica , Ecocardiografia Doppler , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda
7.
Arq Bras Cardiol ; 105(1): 28-36, 2015 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-25993486

RESUMO

BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e' (average) with the reservoir and pump functions (TEF and AEF), and a positive correlation of e' (average) with s' wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An impairment of LA functions in Chagas cardiomyopathy was observed.


Assuntos
Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
8.
Cytokine ; 73(1): 79-83, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25743241

RESUMO

BACKGROUND: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.


Assuntos
Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Masculino , Volume Sistólico
9.
Cytokine ; 73: 79-83, 2015. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1062323

RESUMO

Background: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy,affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the restof the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotalrole in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described.IL-18 could potentially amplify the process by inducing increased expression of IFN-c which in turn canincrease the production of IL-18, thereby creating a positive feedback mechanism. In order to assess thecontribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the associationbetween a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developingChagas cardiomyopathy.Methods and results: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas diseasecardiomyopathy patients (n = 849) and asymptomatic subjects (n = 202). We found a significant differencein genotype frequencies among moderate and severe CCC patients with ventricular dysfunction.Conclusions: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkagedisequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.


Assuntos
Disfunção Ventricular , Doença de Chagas , Miocardite
10.
Nucl Med Commun ; 35(8): 818-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24781009

RESUMO

Heart failure is increasing worldwide at epidemic proportions, resulting in considerable disability, mortality, and increase in healthcare costs. Gated myocardial perfusion single photon emission computed tomography or PET imaging is the most prominent imaging modality capable of providing information on global and regional ventricular function, the presence of intraventricular synchronism, myocardial perfusion, and viability on the same test. In addition, I-mIBG scintigraphy is the only imaging technique approved by various regulatory agencies able to provide information regarding the adrenergic function of the heart. Therefore, both myocardial perfusion and adrenergic imaging are useful tools in the workup and management of heart failure patients. This guide is intended to reinforce the information on the use of nuclear cardiology techniques for the assessment of heart failure and associated myocardial disease.


Assuntos
Prova Pericial , Insuficiência Cardíaca , Agências Internacionais , Energia Nuclear , Medicina Nuclear/métodos , Guias de Prática Clínica como Assunto , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos
11.
BMC Infect Dis ; 13: 587, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24330528

RESUMO

BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage. METHODS: Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. RESULTS: The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. CONCLUSIONS: Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.


Assuntos
Cardiomiopatia Chagásica/genética , Quimiocina CCL2/genética , Predisposição Genética para Doença , Imunidade Inata , Glicoproteínas de Membrana/genética , Receptores CCR5/genética , Receptores de Interleucina-1/genética , Trypanosoma cruzi/fisiologia , Adulto , Idoso , Brasil , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/prevenção & controle , Quimiocina CCL2/imunologia , Feminino , Genótipo , Humanos , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores CCR5/imunologia , Receptores de Interleucina-1/imunologia
12.
PLoS One ; 8(12): e83446, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367596

RESUMO

AIMS: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. METHODS AND RESULTS: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. CONCLUSIONS: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.


Assuntos
Actinas/genética , Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Actinas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Miocárdio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
J Card Fail ; 19(7): 454-60, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23834921

RESUMO

BACKGROUND: The influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. METHODS AND RESULTS: Changes in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with (31)P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac (31)P-MRS. The myocardial phosphocreatine to [ß-phosphate]adenosine triphosphate ratio (PCr/ß-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc-sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/ß-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/ß-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/ß-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/ß-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/ß-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001). CONCLUSIONS: Myocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Teste de Esforço/métodos , Exercício Físico/fisiologia , Miocárdio/metabolismo , Fosfatos/metabolismo , Adulto , Cardiomiopatia Chagásica/diagnóstico , Metabolismo Energético/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
15.
PLos ONE ; 8(12): 1-16, 2013. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1065112

RESUMO

Aims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to alife-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infectedindividuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to diseaseprogression was suggested by familial aggregation of cases and the association of markers of innate and adaptiveimmunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin(ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1gene in CCC pathogenesis.Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The geneticstudy was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and thereplication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower inmyocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping acase-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1gene identified rs640249 SNP, located at the 5’ region, as associated to CCC. Associations are borderline aftercorrection for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype.Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in thepromoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replicationcohort will be useful.Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic ChagasCardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1promoter regions.


Assuntos
Cardiomiopatia Chagásica , Doença de Chagas , Variação Genética
16.
PLoS Negl Trop Dis ; 6(10): e1867, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23150742

RESUMO

BACKGROUND: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. METHODS AND RESULTS: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. CONCLUSIONS: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.


Assuntos
Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/patologia , Quimiocina CXCL10/biossíntese , Quimiocina CXCL9/biossíntese , Polimorfismo Genético , Trypanosoma cruzi/patogenicidade , Adolescente , Adulto , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Resistência à Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
J Card Fail ; 18(8): 654-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22858082

RESUMO

BACKGROUND: The hallmark of Chagas disease (CD) is multifocal myocarditis and extensive fibrosis. We investigated the potential effect of colchicine on myocardial remodeling in experimental CD. METHODS AND RESULTS: One hundred Syrian hamsters were randomly divided into noninfected untreated control (CG), noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage), infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1)) groups. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry with picrosirius red staining. The gelatinolytic activities of matrix metalloproteinase (MMP) 2 were examined with the use of zymography. Myocarditis was described according to the Dallas criteria. Statistical comparisons were performed with parametric analysis of variance and Tukey test. ICVF (%) accumulation was attenuated in infected colchicine-treated animals in the left (CG 0.81 ± 0.13, COLG 0.85 ± 0.13, IG: 1.35 ± 0.31,* ICOLG 1.06 ± 0.19; *P < .05 compared with ICOLG) and right ventricles (CG 1.4 ± 0.36, COLG 1.26 ± 0.14, IG 1.97 ± 0.058,* ICOLG: 1.52 ± 0.23; *P < .05 compared with ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in ICOLG (17,432.8*) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG. CONCLUSIONS: Colchicine had a protective effect on myocardium, indicated by decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and attenuated myocardial inflammation.


Assuntos
Doença de Chagas/tratamento farmacológico , Colchicina/uso terapêutico , Miocardite/tratamento farmacológico , Trypanosoma cruzi , Moduladores de Tubulina/uso terapêutico , Análise de Variância , Animais , Doença de Chagas/patologia , Colágeno , Cricetinae , Modelos Animais de Doenças , Feminino , Fibrose/tratamento farmacológico , Fibrose/patologia , Ventrículos do Coração , Inflamação/tratamento farmacológico , Inflamação/patologia , Metaloproteinase 2 da Matriz , Miocardite/patologia , Miocárdio/patologia
18.
Arq. bras. cardiol ; 96(2): 99-106, fev. 2011. graf
Artigo em Português | LILACS | ID: lil-579616

RESUMO

FUNDAMENTO: A norepinefrina miocárdica está alterada na disfunção ventricular esquerda. Em pacientes com cardiomiopatia chagásica (CC), essa questão ainda não foi discutida. OBJETIVO: Determinar o nível de norepinefrina (NE) miocárdica em pacientes com CC e compará-la em pacientes com doença arterial coronariana (DAC) e relacionar NE miocárdica com a fração de ejeção do ventrículo esquerdo (FEVE). MÉTODOS: Estudamos 39 pacientes com CC, divididos em grupo 1: 21 indivíduos com FEVE normal e grupo 2: 18 com FEVE diminuída. Dezessete pacientes com DAC foram divididos em grupo 3: 12 indivíduos com FEVE normal e grupo 4: 5 indivíduos com FEVE diminuída. Ecocardiografia bidimensional foi usada para medir a FEVE. A NE miocárdica foi determinada através de Cromatografia Líquida de Alta Eficiência (HPLC). RESULTADOS: A NE miocárdica na CC com e sem disfunção ventricular foi 1,3±1,3 e 6,1±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001); na DAC com e sem disfunção ventricular, foi 3,3±3,0 e 9,8±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001). Uma correlação positive foi observada entre a FEVE e a concentração de NE miocárdica em pacientes com CC (p<0,01; r = 0,57) e também naqueles com DAC (p<0,01; r=0,69). Uma diferença significante foi demonstrada entre as concentrações de NE em pacientes com FEVE normal (grupos 1 e 3; p = 0,0182), mas nenhuma diferença foi observada em pacientes com FEVE diminuída (grupos 2 e 4; p = 0,1467). CONCLUSÃO: Pacientes com CC e fração de ejeção global normal apresentam uma denervação cardíaca precoce, quando comparados à pacientes com doença arterial coronariana.


BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment. In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed. OBJECTIVE: To determine the level of myocardial norepinephrine in patients with CC and compare it in patients with coronary artery disease, and to relate myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS: We studied 39 patients with CC, divided into group 1: 21 individuals with normal LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with coronary artery disease were divided into group 3: 12 individuals with normal LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional echocardiography was used to measure LVEF. Myocardial norepinephrine was determined by high-performance liquid chromatography. RESULTS: Myocardial norepinephrine in CC with and without ventricular dysfunction was 1.3±1.3 and 6.1±4.2 pg/μg noncollagen protein, respectively (p<0.0001); in coronary artery disease with and without ventricular dysfunction, it was 3.3±3.0 and 9.8±4.2 pgμg noncollagen protein, respectively (p<0.0001). A positive correlation was found between LVEF and myocardial norepinephrine concentration in the patients with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary artery disease (p<0.01, r=0.69). A significant difference was demonstrated between norepinephrine concentrations in patients with normal LVEF (groups 1 and 3; p = 0.0182), but no difference was found in patients with decreased LVEF (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy and normal global ejection fraction there is an early cardiac denervation, when compared to coronary artery disease patients.


FUNDAMENTO: La norepinefrina miocárdica está alterada en la disfunción ventricular izquierda. En pacientes con cardiomiopatía chagásica (CC), esa cuestión aun no fue discutida. OBJETIVO: Determinar el nivel de norepinefrina (NE) miocárdica en pacientes con CC y compararla en pacientes con enfermedad arterial coronaria (EAC) y relacionar NE miocárdica con la fracción de eyección del ventrículo izquierdo (FEVI). MÉTODOS: 39 pacientes con CC, divididos en grupo 1: 21 individuos con FEVI normal y grupo 2: 18 con FEVI disminuida. Diecisiete pacientes con EAC fueron divididos en grupo 3: 12 individuos con FEVI normal y grupo 4: 5 individuos con FEVI disminuida. Ecocardiografía bidimensional fue usada para medir la FEVI. La NE miocárdica fue determinada a través de Cromatografía Líquida de Alta Eficiencia (HPLC). RESULTADOS: La NE miocárdica en la CC con y sin disfunción ventricular fue 1,3±1,3 y 6,1±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001); en la EAC con y sin disfunción ventricular, fue 3,3±3,0 y 9,8±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001). Una correlación positiva fue observada entre la FEVI y la concentración de NE miocárdica en pacientes con CC (p<0,01; r=0,57) y también en aquellos con EAC (p<0,01; r=0,69). Una diferencia significativa fue demostrada entre las concentraciones de NE en pacientes con FEVI normal (grupos 1 y 3; p = 0,0182), pero ninguna diferencia fue observada en pacientes con FEVI disminuida (grupos 2 y 4; p = 0,1467). CONCLUSIONES: Pacientes con CC y fracción de eyección global normal presentan una denervación cardíaca precoz, cuando son comparados a pacientes con enfermedad arterial coronaria.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cardiomiopatia Chagásica/metabolismo , Doença da Artéria Coronariana/metabolismo , Miocárdio/química , Norepinefrina/análise , Volume Sistólico/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Cromatografia Líquida de Alta Pressão/métodos , Doença da Artéria Coronariana/fisiopatologia , Métodos Epidemiológicos , Coração/inervação
19.
Arq Bras Cardiol ; 96(2): 99-106, 2011 Feb.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-21180891

RESUMO

BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment. In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed. OBJECTIVE: To determine the level of myocardial norepinephrine in patients with CC and compare it in patients with coronary artery disease, and to relate myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS: We studied 39 patients with CC, divided into group 1: 21 individuals with normal LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with coronary artery disease were divided into group 3: 12 individuals with normal LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional echocardiography was used to measure LVEF. Myocardial norepinephrine was determined by high-performance liquid chromatography. RESULTS: Myocardial norepinephrine in CC with and without ventricular dysfunction was 1.3±1.3 and 6.1±4.2 pg/µg noncollagen protein, respectively (p<0.0001); in coronary artery disease with and without ventricular dysfunction, it was 3.3±3.0 and 9.8±4.2 pg/µg noncollagen protein, respectively (p<0.0001). A positive correlation was found between LVEF and myocardial norepinephrine concentration in the patients with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary artery disease (p<0.01, r=0.69). A significant difference was demonstrated between norepinephrine concentrations in patients with normal LVEF (groups 1 and 3; p = 0.0182), but no difference was found in patients with decreased LVEF (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy and normal global ejection fraction there is an early cardiac denervation, when compared to coronary artery disease patients.


Assuntos
Cardiomiopatia Chagásica/metabolismo , Doença da Artéria Coronariana/metabolismo , Miocárdio/química , Norepinefrina/análise , Volume Sistólico/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Cromatografia Líquida de Alta Pressão/métodos , Doença da Artéria Coronariana/fisiopatologia , Métodos Epidemiológicos , Feminino , Coração/inervação , Humanos , Masculino , Pessoa de Meia-Idade
20.
Arq Bras Cardiol ; 95(2): 264-70, 2010 Aug.
Artigo em Inglês, Português | MEDLINE | ID: mdl-20676586

RESUMO

BACKGROUND: Abnormalities in myocardial metabolism have been observed in patients with heart failure of different etiologies. Magnetic resonance spectroscopy (MRS) with phosphorus-31 is a noninvasive technique that allows detection of myocardial metabolic changes. OBJECTIVE: To determine the resting metabolism of high-energy phosphates in patients with Chagas' disease (CD) by MRS with phosphorus-31. METHODS: We studied 39 patients with CD, 23 with preserved ventricular function (PF Group) and 16 with ventricular dysfunction (VD Group), assessed by Doppler echocardiography. MRS of the anterosseptal region was performed in 39 patients and 8 normal subjects (C Group) through a Phillips 1.5 Tesla device, obtaining the phosphocreatine/beta-adenosine triphosphate myocardial ratio (PCr/ß-ATP). RESULTS: The levels of cardiac PCr/ß-ATP were reduced in VD Group in relation to PF Group, and the latter presented reduced levels compared to C Group (VD Group: 0.89 ± 0.31 vs PF Group: 1.47 ± 0.34 vs C Group: 1.88 ± 0.08, p < 0.001). A correlation was found between left ventricular ejection fraction and PCr/ß-ATP in 39 patients (r = 0.64, p < 0.001). Patients under functional class I (n = 22) presented PCr/ß-ATP of 1.45 ± 0.35, and those in functional classes II and III (n = 17), PCr/ß-ATP of 0.94 ± 0.36 (p < 0.001). CONCLUSION: The 31-phosphorus MRS was able to detect non-invasively changes in the rest energy metabolism of patients with Chagas' disease, with and without systolic dysfunction. These changes were related to the severity of heart impairment.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Metabolismo Energético/fisiologia , Espectroscopia de Ressonância Magnética , Fosfatos/metabolismo , Fósforo , Função Ventricular/fisiologia , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Chagásica/metabolismo , Doença de Chagas/metabolismo , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Estudos Prospectivos , Índice de Gravidade de Doença
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