The Relationship between Heart Rate Variability and Serum Cytokines in Chronic Chagasic Patients with Persistent Parasitemia

Llaguno, Mauricio; Pertili, Luiz Antonio Rodrigues de Resende; Silva, Marcos; Bunazar, Pablo; Reges, Ariane Martim; Faleiros, Ana Carolina Guimarães; Lages‐Silva, Eliane; Rodrigues, Virmondés; Silva, Valdo José Dias da; Filho, Dalmo Correia

doi:10.1111/j.1540-8159.2010.03025.x

Cited by 13 publications

(12 citation statements)

References 65 publications

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“…In other studies, IL-10 has been attributed to eliciting an increased susceptibility to infection, regulation of chemokine production (eg. MCP-1) recruiting monocytes/macrophages, endothelial activation with IL-6 production, and increased nitric oxide production [29,42,43]. This study found that IL-10 levels were higher in CC and there was an inverse correlation with EF.…”

Section: Discussionmentioning

confidence: 86%

Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease

Keating

Deng

Fernandes

et al. 2015

International Journal of Cardiology

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Background Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. Methods This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) that were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. Results A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. Conclusions Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.

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Section: Discussionmentioning

confidence: 86%

Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease

Keating

Deng

Fernandes

et al. 2015

International Journal of Cardiology

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“…This finding raises the possibility that the autonomic dysfunction associated with chagasic infection could be an influential or determining cause of immunological alterations contributing to the development and maintenance of chronic Chagas chronic infection. In this regard, an association between cardiac autonomic dysfunction and altered levels of cytokines was recently demonstrated in chagasics with the indeterminate and cardiac forms and with sustained parasitemia; the heart disease patients showed higher concentrations of IL-10 and lower IFN-γ, suggesting some disturbance of the process of immune regulation 89 .…”

Section: Other Possible Effects Of Autonomic Dysfunctionmentioning

confidence: 99%

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

Junqueira Junior

2012

Rev. Soc. Bras. Med. Trop.

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INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

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“…A decrease in HRV is reportedly characterized by autonomic dysfunction and ventricular dysfunction in patients with Chagas disease 18 . Llaguno et al 18 demonstrated autonomic dysfunction in patients with chronic Chagas disease and high cardiovascular risk, but they failed to relate this condition with serum cytokine levels 19 . Our results suggest that TNF-α blockade induces autonomic dysfunction during the acute phase of infection in mice with Chagas disease and that cardiovascular function worsens after treatment.…”

Section: Discussionmentioning

confidence: 99%

Etanercept Induces Low QRS Voltage and Autonomic Dysfunction in Mice with Experimental Chagas Disease

Rodríguez-Angulo¹,

Garcia²,

Castillo³

et al. 2013

Arquivos Brasileiros De Cardiologia

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BackgroundChagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized by disorders of autonomic regulation and action potential conduction in the acute and chronic phases of infection. Although tumor necrosis factor alpha (TNF-α) has been linked to cardiomyopathy in experimental models and in patients with Chagas disease, other reports suggest that TNF-α may exert anti-parasitic actions during the acute phase of infection. ObjectivesThis study aimed to determine the effects of a soluble TNF-α blocker, etanercept, on electrocardiographic parameters in the acute phase of experimental infection with Trypanosoma cruzi. MethodsElectrocardiograms were obtained from untreated infected mice and infected mice who were treated with etanercept 7 days after infection. ECG wave and heart rate variability parameters were determined using Chart for Windows. ResultsEtanercept treatment resulted in a low QRS voltage and decreased heart rate variability compared with no treatment. However, the treated mice exhibited a delay in the fall of the survival curve during the acute phase. ConclusionThe results of this study suggest that although etanercept treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF-α blockade generates a low voltage complex and autonomic dysfunction during the acute phase of infection. These findings indicate that mortality during the acute phase can be attributed to a systemic inflammatory response rather than cardiac dysfunction.

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The Relationship between Heart Rate Variability and Serum Cytokines in Chronic Chagasic Patients with Persistent Parasitemia

Cited by 13 publications

References 65 publications

Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease

Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

Etanercept Induces Low QRS Voltage and Autonomic Dysfunction in Mice with Experimental Chagas Disease

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