Chagasic Hearts Research Articles

Is apoptosis a mechanism of cell death of cardiomyocytes in chronic chagasic myocarditis?

The micropathology of chronic Chagas' myocarditis reveals foci of myocardial cell loss associated with an inflammatory infiltrate composed predominantly of lymphomononuclear cells and interstitial fibrosis. The loss of myocardial cells, a devastating phenomenon in this cardiopathy, has been classically attributed to necrosis. In the present study we examined whether the loss of myocardial cells in human chronic Chagas' heart disease could result from cell death by apoptosis. A total of 11 cases of chronic chagasic myocarditis were studied: four hearts were obtained at autopsy within 8 h after death and seven endomyocardial biopsies were taken from chagasic patients with an arrhythmogenic form of the disease. The coronary arteries of all chagasic cases showed no obstructive lesions. The diagnosis of Chagas' disease was based on previously established criteria. Five cases were selected as controls: three hearts were obtained at autopsy within 8 h after death and two endomyocardial biopsies were taken from nonchagasic patients with normal myocardium morphology. As positive controls we used cardiac muscles of myocardial infarction and rat mammary glands on the fourth day after weaning. The TUNEL method was used to identify apoptotic cells in the myocardium. The expression of p53 protein, which directly or indirectly triggers apoptosis, was evaluated using immunohistochemical technique. A few apoptotic cells were stained in chronic chagasic hearts, both biopsy and autopsy cases. However, the stained nuclei were restricted to the mononuclear infiltrate accounting for about 0.5% of the mononuclear cells in the infiltrate. In contrast, the nuclei of cardiomyocytes in both regions bordering on and distant from the microfoci of myocardial cell loss were not stained by the TUNEL method. Moreover, the expression of the protein p53 in cardiomyocytes in chagasic hearts was absent. The results of the present study demonstrating negative in situ labeling of fragmented DNA associated with absence of expression of p53 provide support to the hypothesis that apoptosis is not the mechanism of cell death in chronic chagasic myocarditis. This reinforces the general opinion that the loss of cardiac muscle fibers in chagasic cardiopathy is produced by necrosis. On the other hand, the present results give support to the concept that apoptosis probably play a role in the clearing of lymphomononuclear cells in the inflammatory infiltrate in chronic chagasic myocarditis.

Persistent Production of Inflammatory and Anti-inflammatory Cytokines and Associated MHC and Adhesion Molecule Expression at the Site of Infection and Disease in ExperimentalTrypanosoma cruziInfections

Trypanosoma cruziinfection in humans and experimental animals often results in a chronic heart and gut inflammation and a dysfunction known as Chagas' disease. Previous studies have shown that the cellular infiltrate in the hearts of animals with chronic Chagas' disease consists mainly of CD8+T cells. In this study, we have used immunohistochemical techniques to further characterize the immunological nature of chagasic heart lesions in three murine models of experimental Chagas' disease. Double-staining immunohistochemistry revealed that 10–30% of the infiltrating CD8+T cells in the hearts of infected mice expressed the activation molecules, IL-2 receptor and CD44. In addition, large numbers of cells producing TNF-α, TGF-β, IL-1α, and IL-6 were consistently observed in the heart lesions, appearing during the acute infection and persisting throughout the chronic stage of infection (>300 days). In contrast, IFN-γ- and IL-10-producing cells were detected in relatively low numbers and only transiently between approximately 3 and 9 weeks postinfection. Cells producing IL-2, IL-4, and IL-5 were not observed in the hearts of mice at any point during the infection. The appearance of cytokine-producing cells in the hearts correlated with an increased local expression of class I and class II MHC molecules and adhesion molecules (ICAM-1, LFA-1, VLA-4, and VCAM-1). The results of this study suggest that the chronic inflammation in chagasic hearts is highly active and associated with a stable immunological pattern extending from the early acute stage of the infection through the late chronic stage. The pattern of cytokine production in heart is distinct from that observed in lymphoid organs and is not suggestive of an association between particular classes of cytokines and disease development. Instead it appears that both inflammatory and antiinflammatory cytokines determine the pattern of the cellular response and the severity of disease inT. cruziinfection.

Histopathological criteria of myocarditis. A study based on normal heart, chagasic heart and dilated cardiomyopathy.

This work is a detailed study of the relevance of three sets of criteria to define myocarditis: Dallas meeting criterion, Edwards criterion and Dallas meeting criterion modified by the authors. Two groups were evaluated: normal autopsied hearts and endomyocardial biopsy from chronic chagasic patients at high risk of having myocarditis. Furthermore, endomyocardial biopsies from patients with dilated cardiomyopathy (DCM) were also evaluated. Applying the Edwards criterion, incidences of myocarditis in normal and chagasic hearts were 0% and 67% while with Dallas meeting criterion they were 0% and 42% and using our criterion the incidences were 0% and 92% respectively. In endomyocardial biopsies from DCM patients, the incidence of myocarditis was 7% with Edwards criterion, 22% with Dallas meeting and 33% with the authors own criterion. The authors concluded that their criterion, which defines myocarditis as the presence of inflammatory mononuclear cells enclosing more than 2 lymphocytes/400X aggregated to the cardiac fiber sarcolemma, is the most appropriate criterion of the three. Myocarditis was found in 33% of the 27 endomyocardial biopsy specimens from patients with DCM.

O pêso do coração em chagásicos crônicos

Os AA. estudaram o pêso do coração em 740 chagásicos crônicos. O pêso do coração de indivíduos que faleceram com e sem I. C. C. e sem "megas" variou de 100 a 1.075 g. O maior número (564) era de corações com I. C. C. e pesavam entre 201 e 800 g, e apenas 45, sem I. C .C., pesavam entre 151 e 500 g. O peso do coração de indivíduos que faleceram com e sem I. C. C. mas com "megas" variou de 100 a 750 g. O maior número de corações com (39) e sem (60) I. C. C. pesou entre 101 e 450 g. O pêso médio dos corações chagásicos (740) foi de 435 ±5,6 g. Já o pêso médio dos corações chagásicos com e sem I. C. C., sem "megas' foi de 479±5,6 g e o pêso médio dos corações com e sem I. C. C. e com "megas" foi de 314±12,6 g. A análise estatística aplicada demonstrou haver diferença significativa en¬tre as duas médias. A hipotrofia constatada nos corações de indivíduos portadores de "megas", especialmente de megaesôfago, está relacionada com o estado de desnutrição e não com a idade.