RESUMO
Trypanosoma cruzi infection in humans leads to progression to chronic chagasic myocarditis (CCM) in 30% of infected individuals, paralleling T cell inflammatory infiltrates in the heart tissue. T-cell trafficking into the hearts of CCM patients may be modulated by in situ expression of chemotactic or haptotactic molecules, as the chemokine CXCL12, the cytokine tumor necrosis factor-alpha (TNF-α), and extracellular matrix proteins (ECM), such as fibronectin. Herein we evaluated the expression of fibronectin, CXCL12, and TNF-α in the myocardial tissue of T. cruzi seropositive (asymptomatic or with CCM), as well as seronegative individuals as healthy controls. Hearts from CCM patients exhibited enhanced expression of these three molecules. CXCL12 and TNF-α serum levels were also increased in CCM individuals. We then evaluated T lymphocytes from chronic chagasic patients by cytofluorometry, in terms of membrane expression levels of molecules involved in cell activation and cell migration, respectively, HLA-DR and the VLA-4 (very late antigen-4, being one integrin-type fibronectin receptor). Indeed, the expression of HLA-DR and VLA-4 was enhanced on T lymphocytes from chagasic patients, especially in the CCM group. To further approach the dynamics of T cell migratory events, we performed fibronectin-, TNF-α-, and CXCL12-driven migration. Peripheral blood mononuclear cells (PBMCs) and T cells from CCM patients presented an ex vivo enhanced migratory capacity driven by fibronectin alone when this ECM protein was placed in the membrane of transwell migration chambers. When TNF-α was previously placed upon fibronectin, we observed a further and significant increase in the migratory response of both PBMCs and T lymphocytes. Overall, these data suggest the existence in patients with chronic Chagas disease of a cardiac inflammatory infiltrate vector that promotes the recruitment and accumulation of activated T cells, driven in part by enhanced tissue expression of fibronectin and TNF-α, as well as the respective corresponding VLA-4 and TNF receptors.
Assuntos
Doença de Chagas , Integrina alfa4beta1 , Fator de Necrose Tumoral alfa/genética , Humanos , Leucócitos Mononucleares , Linfócitos TRESUMO
Objetivo: Avaliar eficácia e tolerância do uso empírico de amiodarona, a longo prazo, em portadores d e Miocardiopatia Chagásica Crônica (MCC) e Taquicardia Ventricular Sustentada (TVS). Casuística e Métodos: Trinta e cinco portadores de MCC e TVS, 18 (51% ) dos quais, refratários a outras drogas antiarritmicas. A dose de impregnação variou de 600 a 1200 (média de 883 ± 239) mg/dia, por período de uma a quatro semanas. A dose de manutenção foi reduzida progressivamente à média de 356 ± 125 mg/dia ao final de seis a 80 (média de 27 ± 20) meses. Foram construídas curvas de estimativa de recorrência clínica, morte súbida e morte cardíaca, segundo o método de Kaplan e Meier e comparadas variáveis clínicas na avaliação de risco de recorrências e morte súbita, através dos testes do Qui-quadrado de Pearson e t de Student.
Purpose: To evaluate the efficacy and safety of long-term empiric amiodarone therapy in patients with recurrent Sustained Ventricular Tachycardia (SVT) and Chronic Chagasic Myocarditis (CCM). Patiens and Methods: Thirty-five patients with CCM and SVT, eighteen (51%) of them were refratary to other antiarrhythmic drugs. The Amiodarone loading dose was between 600 and 1200 mg/day, mean of 883 ± 239 mg/day, from a period of one to four weeks. The maintenance dose was decreasing in the follow-up period, it fell down to 356 ± 125 mg/day at the end of six to 80 (mean = 27 ± 20) months. Cumulative, event-free interval curves were generated by the Kaplan-Meier method. Clinicals variables were compared with the use of the Student t-test or by means of chi-square tests.