Sera From Chronic Chagasic Patients With Complex Cardiac Arrhythmias Depress Electrogenesis and Conduction in Isolated Rabbit Hearts

Oliveira, S F; Pedrosa, Roberto Coury; Nascimento, José; Carvalho, Antônio Carlos Campos de; Masuda, Masako Oya

doi:10.1161/01.cir.96.6.2031

Cited by 81 publications

(55 citation statements)

References 17 publications

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“…The production of autoantibodies against beta1 and beta2-adrenoreceptors correlated with primary electrical cardiac abnormalities (Chiale et al 1995). It was also demonstrated that sera from chronic chagasic individuals interfere with electric and mechanical activities of embryonic myocardial cells in vitro (Costa et al 2000, Kaplan et al 1997 and affect cardiac electrogenesis and conduction when perfused in the rabbit heart (de Oliveira et al 1997). These alterations in heart-cell function seem to result from the binding of antibodies to β-adrenergic and M2-cholinergic receptors on the myocardial cell surface (Costa et al 2000, de Oliveira et al 1997, Kaplan et al 1997.…”

Section: Autoimmune Responses In Cchcmentioning

confidence: 96%

“…It was also demonstrated that sera from chronic chagasic individuals interfere with electric and mechanical activities of embryonic myocardial cells in vitro (Costa et al 2000, Kaplan et al 1997 and affect cardiac electrogenesis and conduction when perfused in the rabbit heart (de Oliveira et al 1997). These alterations in heart-cell function seem to result from the binding of antibodies to β-adrenergic and M2-cholinergic receptors on the myocardial cell surface (Costa et al 2000, de Oliveira et al 1997, Kaplan et al 1997. Thus, by stimulating the production of autoantibodies against certain self-antigens, T. cruzi infection may cause disturbances in heart cell functions, which may lead to complications associated with CChC.…”

Section: Autoimmune Responses In Cchcmentioning

confidence: 99%

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The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Soares

Pontes-de-Carvalho

Ribeiro-dos-Santos

2001

An. Acad. Bras. Ciênc.

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Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.

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Section: Autoimmune Responses In Cchcmentioning

confidence: 96%

Section: Autoimmune Responses In Cchcmentioning

confidence: 99%

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Soares

Pontes-de-Carvalho

Ribeiro-dos-Santos

2001

An. Acad. Bras. Ciênc.

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“…The inflammatory and fibrotic processes may damage sinus cells, destroy the innervation, and cause significant barriers to sinus node impulse progression 12. However, autoantibodies reported in ChHD may exert sometimes effects in favour of increment or decrease in heart chronotropism, depending on the type of antibody or patient characteristics 13, 14, 15…”

Section: Discussionmentioning

confidence: 99%

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

et al. 2017

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AimsThe SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients.Methods and resultsSHIFT was a randomized, double‐blind, placebo‐controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta‐blocker. ChD HF presented a poor prognosis (all‐cause mortality at 2 years was ~60%). The mean twice‐daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all‐cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope.ConclusionsChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit–risk profile in ChD HF patients.

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“…Functional antibodies against adrenergic and muscarinic (M2) cholinergic receptors were found in serum from arrhythmic CCC patients. These antibodies were capable of inducing arrhythmia in explanted rabbit hearts (DE OLIVEIRA et al 1997; Tables 1 and 2). The presence of functionally active anti-receptor antibodies may also correlate with dysfunction of the autonomic nervous system, rather than with heart symptomatology (GOIN et al, 1997).…”

Section: Immunopathogenesis Of Chagas Disease Cardiomyopathymentioning

confidence: 99%

Chagas disease cardiomyopathy: current concepts of an old disease

Bilate¹,

Cunha‐Neto

2008

Rev. Inst. Med. trop. S. Paulo

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SUMMARYChagas disease continues to be a significant public health problem, as ca. 10 million people are still infected with T. cruzi in Latin America. Decades after primary infection, 30% of individuals can develop a form of chronic inflammatory cardiomyopathy known as Chagas disease cardiomyopathy (CCC). Data from both murine models and human studies support the view that an autoimmune response as well as a parasite-driven immune response involving inflammatory cytokines and chemokines may both play a role in generating the heart lesions leading to CCC. This review aims to summarize recent advances in the understanding of the immunopathogenesis of Chagas disease cardiomyopathy.

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Sera From Chronic Chagasic Patients With Complex Cardiac Arrhythmias Depress Electrogenesis and Conduction in Isolated Rabbit Hearts

Abstract: Antibodies of ChA+ patients decrease heart rate and induce AV conduction block in isolated adult rabbit hearts through activation of muscarinic receptors.

Cited by 81 publications

References 17 publications

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

Chagas disease cardiomyopathy: current concepts of an old disease

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